Pain Digibook 2020 by New Media Medical

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A dose of care.

FOR THE

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Headaches

Pain and fever

1-6

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South Africa’s No.1 Pain Relief7* *Within the tablets and capsules category

Contains Paracetamol. References: 1. Panado® Tablets approved professional information, June 2005. 2. Panado® Capsules approved package insert, August 1984.12. 3. Panado Effervescent (Tablet) approved professional information, July 1992. 4. Prescott LF. Paracetamol: past, present, and future. Am J Ther 2000;7(2):143-7. 5. Ennis ZN, Dideriksen D, Vægter HB, et al. Acetaminophen for Chronic Pain: A Systematic Review on Efficacy. Basic & Clinical Pharmacology &Toxicology 2016;118:184–189. Doi: 10.1111/bcpt.12527. 6. Moller PL, Sindet-Pedersen S, Petersen CT, et al. Onset of Acetaminophen Analgesia: Comparison of Oral and Intravenous Routes After Third Molar Surgery. Br J Anaesth 2005 May;94(5):642-8. 7. IRI Data for MAT March 2020. S0 S1 Panado® Tablets. Each tablet contains paracetamol 500 mg. Reg. No. B/2.8/858. S0 S1 Panado® Capsules. Each capsule contains paracetamol 500 mg. Reg. No. S/2.8/57. For full prescribing information refer to the package insert approved by the medicines regulatory authority. Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021 South Africa. Tel. +27 11 635 0000. www.adcock.com. 202005291036752. 14566T

Welcome to Medical Chronicleâ&#x20AC;&#x2122;s

PAIN DIGIBOOK, sponsored by Adcock

Here you will find some articles on this diverse and dynamic field that have been featured in Medical Chronicle.

Happy reading!

Contents 4 War on pain

7 Dealing with post-stroke pain 8 Muscle pain 101 10 Pain nociceptive vs neuropathic 12 What to do for back pain? 14 Pain in the gut 17 Adding a 'green prescription' to pain management 18 A guide to tapering opioids

CPD

20 Osteoarthritis pain, joint function and QoL PAIN CPD

s and strains

view

25 Postoperative pain a psychological assessment 27 Etoricoxib most cost-effective initial NSAID treatment 30 Myofascial pain syndrome on the increase

on type of musculoskeletal pain.

Partial tears can result from a single umatic event (eg, penetrating trauma) repeated stress (chronically, causing ndinopathy). Motion is often intact, but rtial tears may progress to complete

23 Dysmenorrhoea: Prevalent and undertreated

33 Shrugging off shoulder pain 34 Pain: A sensory and emotional experience 38 Simple analgesics could prove effective in the management of tension headaches 40 Medical cannabis - What's the evidence? 41 Managing chronic pain during the Covid-19 pandemic 44 Do NSAIDs make Covid-19 worse? 45 Sprains and strains: An overview 48 Guidelines: treating migraine in children 49 Migraine treatment restore anatomy and function. Prognosis and treatment vary greatly depending on the location and severity of the injury.

COMPLICATIONS

significant soft-tissue injuries. â&#x20AC;˘ Vascular injuries: Rarely, what appears to be a severe sprain may be a spontaneously reduced dislocation (eg, of the knee), which may be

MEDICAL CHRONICLE 3

PAIN FOCUS

War on pain

A recent audit in a South Africa healthcare setting found that the prevalence of pain in hospitalised paediatric patients (0-18 years) was high, but under-recognised and under-treated. The audit was the first of its kind in South Africa.1

ordona et al 1 found that 87% of the paediatric patients (n=63) included in their study, reported having pain at the time of admission, while 29% reported pre-existing (possibly chronic) pain. About 50% experienced abdominal pain, followed by musculoskeletal pain

and headache. The majority of children experienced some pain during their hospitalisation (87%). A quarter of patients were experiencing pain during the interview and 37% reported being in severe pain.1 Some 34% and 22% of respondents considered pain caused by needle stick

and surgery as their worst pain experience, respectively. This was followed by acute illness (18%), procedures (14%), and trauma and injury (11%).1 Although needle stick was the most common cause of ‘worst pain’, its intensity was the lowest of all the ‘worst pain’.

Procedures and surgery had the highest intensity with a median pain score of 10 and 9, respectively.1 Only 16% of patients who experienced pain were assessed using a validated pain scoring tool and 11% had only one pain assessment within the past 24 hours. No medical patient was assessed with a validated tool. About 82% of patients who experienced pain during the past 24 hours, had been prescribed analgesic medication. The majority of those without prescribed analgesia were medical patients (80%). The majority of patients (71%) indicated that they would move to a different health facility if better pain management was offered there.1 WHAT SEEMS TO BE THE PROBLEM? Albertyn et al2 assessed the challenges associated with paediatric pain management in sub-Saharan Africa. The team found that paediatric pain management in the region has been left largely unaddressed. The reasons for this include: LACK OF ANALGESIC MEDICINE The supply of analgesic medicines – particularly narcotics – is problematic in most developing countries. Even when available, access barriers will prevent the distribution of these drugs. Estimates indicated that almost 80% of those diagnosed with cancer do not have access to analgesic medicine. In Africa, 39% of palliative care providers do not have access to strong opioids, while for 41%, morphine was not available. LACK OF EDUCATION AND ACCESS TO INFORMATION African healthcare workers are faced with limited access to literature, expensive textbooks on pain, and a lack of available training, when attempting to learn about childhood pain. Few are trained to recognise, measure and assess pain, and anxiety in paediatric patients. In addition, very little, if any under – and post graduate training specifically in paediatric pain management exists at university level.

400 mg paracetamol

8 mg codeine phosphate

200 mg meprobamate

ATTITUDINAL BARRIERS Language barriers and cultural differences all impact on the management and assessment of pain in children. Pain management is often dependant on the attitudes, culture and believes of health practitioners and is often tarnished by myths and misconceptions. Communication and cultural barriers may place limitations on the child’s ability to recount pain and anxiety to those responsible for care. Health professionals have to be sensitive to the variations in children’s responses to pain, as well as communication styles, as the meaning of pain varies between cultures.

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PAIN FOCUS

LEGAL BARRIERS Policies today focus on preventing drug abuse, instead of providing pain relief. In many countries more attention is given to the war on drugs (crime) than the war on pain. Regulations to prevent drug abuse contributed to a fear of drug dependence, which in turn, led to physicians avoiding prescribing opioids, and a subsequent loss of knowledge on how to use them. Albertyn et al2 proposed the following solutions: • Increase awareness of pain as a physical and emotional insult, which if not treated results in significant morbidity • Provide for the resources needed in pain management • Access to appropriate analgesic drugs is as essential as is adequate training on the responsible use of these drugs • Pain management should be seen as a priority in healthcare provision, and, as such, will require the distribution of protocols, and the setting of minimum standards • Support from governments and policymakers is vital and must be included in the development of pain management standards and protocols. Only then will the access to pain relief be seen as a basic human right. RELIEF OF PAIN IS A BASIC HUMAN RIGHT In 2004, the World Health Organization (WHO) and the International Association for the Study of Pain (IASP) declared that the relief of pain is a human right. This was expanded upon in the 2010 Declaration of Montreal, which stated that access to pain management is a fundamental human right and it is a human rights violation not to treat pain.1 The IASP defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. Acute pain is the expected physiological response to a noxious chemical, thermal or mechanical stimulus, and usually accompanies surgery, traumatic injury, tissue damage or inflammatory

processes. It is self-limiting and typically resolves over days to weeks, but it can persist longer as healing occurs. Chronic pain is defined as intractable pain that exists for three or more months despite adequate treatment.3 PAIN ASSESSMENT TOOL The FLACC scale was developed as a more practical alternative to existing pain scales and first published in 1997. It is a composite of five behaviours considered indicative of pain that can be detected and graded by an observer and easily remembered using the acronym FLACC (face, legs, activity, cry and consolability).5 Each item is scored on a 0–2 scale resulting in a maximum score of 10. The FLACC scale was originally designed and validated for use in infants and children aged two months to seven years to measure postoperative pain. The original instructions for use recommended observing the child for one–five min and matching the observed behaviours to those described in the scale for each item.5 MULTIDISCIPLINARY APPROACH TO PAEDIATRIC PAIN MANAGEMENT According to the IASP recommendations, children with chronic pain should be treated in multidisciplinary outpatient clinics where the biopsychosocial model of pain prevails, however a large number of patients do not have access to them.1 According to Wren et al3, multidisciplinary pain management treatments incorporating pharmacological and integrative non-pharmacological therapies have become the gold standard of care. Integrative non-pharmacological therapies include modalities eg cognitive behavioural therapy (CBT), mindfulness, medical hypnosis, and acupuncture.3 TREATMENT FOR ACUTE PROCEDURAL AND POSTOPERATIVE PAIN Opioid therapy is the cornerstone of treatment for acute procedural and postoperative pain and is regularly prescribed for severe and debilitating chronic pain conditions. Currently there

are no consensus guidelines on prescribing opioids for chronic pain in paediatric patients. Wren et al recommend that paediatricians should use their best judgment when using opioids after appropriate use of nonopioid alternatives.3 Although beneficial, opioid therapy may have side effects, limited efficacy and potential negative outcomes. Side effects including respiratory depression, constipation, cognitive dysfunction, and psychiatric comorbidities. Persistent opioid use is also associated with physical tolerance, dependence, and addiction, as well as heightened pain sensitisation.3 While acute pain management has historically emphasised the use of opioids, multimodal analgesia treatment incorporates opioid-sparing adjuvants targeting specific aspects of the nociceptive and neuropathic pain physiology. Nociceptive analgesics include acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDS), and glucocorticoids. Neuropathic analgesics commonly include gabapentinoids, lidocaine, ketamine and alpha 2 agonists. Regional anaesthesia and injection of local anaesthetics are also regularly utilised to allow targeted analgesia to a specific surgical area. These agents provide safe and effective analgesia and sedation and may help reduce the need for opioid therapies. CHRONIC MULTIDISCIPLINARY PAIN MANAGEMENT When acute pain transforms to chronic pain, the consideration of multidisciplinary care may become even more central in facilitating patient comfort, decreasing reliance on pharmacological therapy, and improving functionality.3 In the management of chronic pain, the emphasis shifts from immediate analgesia to extended pain management services and facilitation of function across domains (eg performance of activities of daily living). A multidisciplinary approach to chronic pain management has therefore increasingly become the standard of care in paediatric pain management settings. Chronic pain

treatment places a central emphasis on integrative non-pharmacological techniques, minimising side effects, and ideally providing the child skills they can use to manage their symptoms independently. The utility of integrative nonpharmacological therapies in pain management of complex patients is often only discussed when all pharmaceutical therapy options have been exhausted. By then, the patient may begin to feel that medical care is somehow being limited or withdrawn, or that using integrative nonpharmacological therapies indicates that the ‘pain is in their head’. This can lead to patients and families feeling resistant to learning and incorporating these essential integrative non-pharmacological pain management tools. In multidisciplinary chronic pain management, integrative nonpharmacological therapies are incorporated in early phases of treatment, along with appropriate pharmacological interventions to provide optimal care for complex paediatric patients. Pharmacological interventions in this setting often include analgesics such as acetaminophen and NSAIDs, gabapentinoids, clonidine, tricyclic antidepressants, and where appropriate serotonin-norepinephrine reuptake inhibitors. Another novel adjuvant therapy that deserves mention as a possible opioid sparing agent, cannabidiol (CBD), is gaining popularity in multimodal pain management. CBD is the non-psychoactive cannabinoid identified in cannabis, while tetrahydrocannabinol (THC) is responsible for the hallucinogenic side effects of cannabis. Opioids are typically minimised in chronic pain management, as the analgesic benefits of opioids are often offset by their long-term negative side effects such as constipation, nausea, vomiting and sedation, as well as the risk of tolerance, dependence, opioid-induced hyperalgesia and addiction. If opioids are deemed clinically necessary, weak opioids like tramadol or hydrocodone can be used in the initial treatment phase but stronger opioids may be needed with recalcitrant pain. Regional anaesthesia also may play less of a role, as the duration of the local anaesthetic and length of time a catheter can be safely inserted may not provide longer-term analgesic benefit. INTEGRATIVE NONPHARMACOLOGICAL THERAPIES Cognitive behavioural therapy A growing body of literature demonstrates the efficacy of CBT protocols for children, teenagers, and adults with chronic pain. This evidence-based treatment is well accepted by patients and providers and is increasingly available to paediatric patients. Although youth in more remote areas may have limited access to cognitive behavioural interventions for chronic pain, the advent of web-based treatments holds promise for reaching a wider paediatric audience. Mindfulness-based interventions Substantive findings support the use of MEDICAL CHRONICLE 5

PAIN FOCUS mindfulness interventions among adults with chronic pain. While preliminary research among paediatric pain populations demonstrates feasibility and acceptability of MBI’s among youth, further research to investigate adaptations of mindfulness protocols for children and adolescents with chronic pain is needed. Clinical judgment is recommended until published research can better guide the use of MBIs among youth with pain. That being said, mindfulness interventions may be low cost or free adjunctive treatments that have fewer side effects as compared to pharmacologic interventions.

Hypnosis Like MBIs, hypnosis is a well-established integrative non-pharmacological intervention for chronic pain management among adults, and there is a smaller but growing research base for paediatric pain management and hypnosis. While preliminary evidence is promising, more research will be necessary before providers can confidently assert that hypnosis aides in pain management in paediatric populations. Acupuncture Acupuncture appears to be an effective integrative non-pharmacological therapy

in the management of acute postoperative pain and neonatal abstinence syndrome, and there is some preliminary evidence for chronic paediatric pain. Additional basic and clinical research is needed to adequately characterise the mechanisms of acupuncture and clinical effects on pain and withdrawal symptoms in paediatric populations. Given that acupuncture has been shown to be a welltolerated and acceptable intervention among youth, feasible to implement in clinics, and has a low side effect profile, it should be considered for incorporation into multidisciplinary analgesia for youth with acute and chronic pain.3

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THE MORE THINGS CHANGE, THE MORE WE STAY THE SAME Doctors and specialists have been prescribing Myprodol® for more than 30 years1 for the effective treatment of mild to moderate pain of inflammatory origin with or without fever.

PAEDIATRIC PAIN REHABILITATIVE PROGRAMMES Intensive interdisciplinary pain treatment (IIPT) programmes are becoming a popular treatment choice for children with chronic pain who exhibit significant functional disability and are unable to progress in an outpatient setting or for those who lack the proper resources in their local environment.3 IIPT involves patient and family participation in either an inpatient or outpatient day hospital setting with coordinated interventions among at least three disciplines including pain or rehabilitation physicians, psychologists, and physical and occupational therapists.3 A longitudinal case series of 56 patients ages eight to 18 suffering from Complex Regional Pain Syndrome (CRPS) showed that an IIPT programme led to improvements in functional disability, pain symptoms, medication use and emotional functioning.3 Another study showed that IIPT was superior to outpatient treatment with significantly larger improvements in functional disability, pain-related fear, and readiness to change among children with chronic pain.3 Bruce et al examined key functional outcomes following a three-week IIPT for adolescents (12 to 18 years) with chronic pain. Maintenance of gains was evaluated at three-month follow-up.4 Participants (n=171) completed measures of functional disability, depressive symptoms, pain catastrophising, opioid use, school attendance, and pain severity at admission. Significant improvements were observed at the end of the programme. These improvements appeared to be maintained or further improved at threemonth follow-up. Nearly 14% of the patients were taking daily opioid medication at admission to the programme. All adolescents were completely tapered off of these medications at the end of the three-week programme and remained abstinent at three-month follow-up.The authors concluded that the findings of their study support interdisciplinary paediatric pain rehabilitation as effective in improving functioning and psychological distress even when discontinuing opioids. CONCLUSION Multidisciplinary pain management, including pharmacological and integrative non-pharmacological therapies, has been demonstrated to be efficacious in the treatment of both acute and chronic pain in paediatric patients.

Why change when you know it works?

Original. Dependable. Since 1987.1 Reference: 1. Myprodol® Capsules approved package insert, May 1987. MYPRODOL® Capsules. Each capsule contains codeine phosphate 10 mg; ibuprofen 200 mg; paracetamol 250 mg. Reg. No. T/2.8/244. For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority. 202008141051764. Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021, South Africa. Tel. +27 11 635 0000. www.adcock.com.

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REFERENCES Cardona CV, Rajah C, Nosisi Y et al. An audit of paediatric pain prevalence, intensity, and treatment at a South African tertiary hospital. Pain Reports, 2019. Albertyn R, Rode H, Millar AJ and Thomas J. Challenges associated with paediatric pain managementin Sub Saharan Africa. Int J Surg, 2009. Wren AA, Ross AC, Golianu B et al. Multidisciplinary Pain Management for Pediatric Patients with Acute and Chronic Pain: A Foundational Treatment Approach When Prescribing Opioids. Children, 2019 Bruce BK, Ale CM, Harrison TE et al. Getting back to living: Further evidence for the efficacy of an interdisciplinary pediatric pain treatment program. Clin J Pain.

PAIN FOCUS

Dealing with post-stroke pain

We all know to act quickly in a patient presenting with stroke. However, in this urgency, it is easy to forget the long-term silent complications that may accompany the patient. In that acute phase, no one thinks of the risks of post-stroke pain.

TROKES ARE THE second most common cause of mortality and the third most common cause of disability worldwide. Annually, there are 795 000 new strokes in the United States alone, with a higher incidence in low-income countries. Post-stroke pain is common. It remains underdiagnosed and undertreated. Poststroke pain is associated with depression, cognitive dysfunction and an impaired quality of life. Of those patients with poststroke pain, 70% will experience pain on a daily basis.A Swiss study on pain poststroke, found moderate-to-severe pain in 32% of patients on the visual analogue scale (VAS) after four months. At sixteen months post stroke, only 21% of patients had moderate- to-severe pain, but the pain intensity was more severe. They concluded that late pain post-stroke profoundly affects patient well-being. RISK FACTORS

COMMON REASONS FOR POSTSTROKE PAIN This article will discuss common reasons for post-stroke pain, as well as the management thereof. This will hopefully increase awareness and improve patient outcomes. SPASTICITY-RELATED PAIN About 15% of patients develop some sort of increased muscle tone within a week post stroke. About 72% of patients with spasticity experience daily pain. A mixture

of neuropathic and nociceptive mechanisms plays a role in this pain; neuronal networks that mediate pain and spasticity might overlap at spinal and cerebral level, there might be abnormal loading on muscles as well as changes in the rheologic muscle properties. Focal, multifocal and regional spasticity can be managed by botulinum A or focal alcohol/phenol neurolysis, whereas a more generalised spasticity will also benefit from oral or intrathecal baclofen.

form of central post-stroke pain (CPSP), with onset mostly three to six months post-stroke. The onset is usually gradual, neuropathic in nature, but severe. The pain component may be constant or intermitted, severely impacting on quality of life, and difficult to manage. CPSP is commonly seen with thalamic lesions, as well as infarcts in the lateral medulla, but can occur with any event involving the spinothalamic tract, as well as in cortical parietal strokes, more if the R hemisphere is involved.

SHOULDER PAIN Common in 25%-50% of patients, mainly due to glenohumeral subluxation and contractures. Onset can be within three weeks and risk factors include upper limb weakness, R hemisphere lesions, spasticity, stroke severity, sensory abnormality and abnormal rheumatological examination The development of shoulder pain is multifactorial. Glenohumeral subluxation can even occur immediately after the stroke due to the flaccid tone, but do not forget impingement, rotator cuff tears, biceps tendonitis and complex regional pain syndrome (CRPS). Complications of subluxation can include CRPS and brachial plexus injuries. Management of shoulder pain includes prevention, passive range of movements, mechanical stabilisation, simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDS), physiotherapy, electrical stimulation (transcutaneous electrical nerve stimulation and functional electrical stimulation), botulinum A and surgery.

CONTRACTURES AND PAIN Permanent shortening of the muscle and joint develop in response to prolonged hypertonic spasticity in a concentrated muscle area. Contractures develop in 50% of patientsâ&#x20AC;&#x2122; six-months post-stroke. Treatment remains controversial, since regular stretch treatment has not been shown to have long-term impact on joint mobility, pain or quality of life. There has been some response to surface electrical stimulation in the elderly, and the use of isokinetic apparatus, which is velocity dependant exercise, shows more promise than regular stretching. CENTRAL POST-STROKE PAIN A third of post-stroke pain presents in the

Treatment may be trail-and-error, with up to 66% of patients in studies complaining of no or inadequate treatment for this pain. We know from numerous studies that tricyclic antidepressant drugs (TAD), selective serotonin reuptake inhibitors, lamotrigine, gabapentin and pregabalin are effective in managing these symptoms. There is also evidence for ketamine and lidocaine usages for acute relief. There is a small retrospective study showing improvement on a short course oral methylprednisolone. A recent study looking at mechanism-based therapeutics stated that electrical motor cortex stimulation remains superior to deep brain stimulation, but the invasiveness of the procedure limits the clinical usage. The current preference is thus for non-invasive transcranial magnetic stimulation. COMPLEX REGIONAL PAIN SYNDROME CRPS in the post-stroke patient typically develops in the upper limb, also called the shoulder-hand syndrome. Incidence post stroke varies from 2%-49%. Proposed pathophysiology includes impaired biomechanics of the glenohumeral joint, alterations in thalamic perfusion, cortical sensory abnormalities, local inflammatory

response, a relative hypoxia due to reduced capillary oxygenation, and local muscle acidosis. CRPS typically present with neuropathic pain, trophic changes of the nails, skin and hair, vasomotor and sudomotor changes, as well as motor limitations. Mainstay of treatment is to prevent and reduce pain, maintain joint mobility, and to restore function. Treatment remains difficult, but there is good evidence for occupation therapy and physiotherapy, with oedema control and desensitisation techniques. Stellate ganglion nerve blocks, imagery or mirror therapy, drugs like memantine, gabapentin, carbamazepine, TAD, bisphosphonates and glucocorticoids are also effective. According to the European Federation of Neurological Societies guidelines there is class I level B evidence for spinal cord stimulation (SCS) in thus subgroup of patients. SCS does not only have a simple anti-nociceptive action. It can also modulate the spontaneous and evoked elements of neuropathic pain, including allodynia, it has an anti-ischaemic action, both cardiac and peripheral, with normalisation of the autonomic manifestations of CRPS. POST-STROKE HEADACHES Chronic headaches post-stroke are common, with headaches at stroke onset a predictor of headaches after six months. The risk of headache post-stroke increases with a history of tension-type headaches (TTH) prior to the stroke. Headaches post stroke can fall in one of four categories: TTH, migraine, medication overuse headaches or due to side effects of medication (dypiridamole or certain antihypertensives) used in the stroke patient. The proposed mechanism is stimulation of the trigeminovascular system due to direct brain injury, as well as damage, disruption or reinnervation of the pain pathways. Headaches post stroke is more common when the stroke involved the posterior circulation. If ipsilateral, it is always on the side of the stroke. The severity does not directly correlate with the size of the stroke. In the group of intracerebral haemorrhage patients, newonset headaches were mainly TTH and significantly associated with depression. Alcohol has been shown to be a great precipitant in these patients. CONCLUSION Pain post-stroke is a common phenomenon, with multiple contributing mechanisms. The identifications remain challenging and careful enquiry and proper examination will increase the diagnosis of pain post-stroke.Proper and correct treatment will not only improve mood and quality of life, but also plays a role in the rehabilitation process. WRITTEN BY: Dr Natanya Fourie, neurologist, Pretoria MEDICAL CHRONICLE 7

PAIN FOCUS

Muscle pain 101 Excessive or unusual pain and discomfort felt in the muscles, tendons, ligaments, and joints, muscle pain can be chronic (persistent and long-lasting) or acute (sudden onset).

Do NOT let muscle pain CRAMP their style. Spasmend eﬀectively relieves painful muscular spasm. Indications: Generalised pain associated with tension. Ingredients: Each tablet contains Mephenesin 150 mg, Paracetamol 500 mg Dosage - Adults: One or two tablets every four hours. The maximum dosage is eight tablets per day.

S2 Spasmend ® . A2.8. Each tablet contains mephenesin 150 mg, paracetamol 500 mg. Ref. No. B1490 (Act 101/1965). For full prescribing information refer to the package insert approved by the medicines regulatory authority. Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021, South Africa. Tel. +27 11 635 000 www.adcock.com 202009141057187

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OSSIBLE CAUSES Muscle pain can have many different causes. Most commonly, muscle pain occurs shortly after an unaccustomed bout of exercise and is simply the result of excessive loading and tension on the muscles, which develop microscopic tears as a result. These tears heal within 72 hours, but pain and inflammation accompany the healing process. This is known as delayed onset of muscle soreness, or DOMS. The pain will usually disappear within three days of the exercise bout. Muscle pain at a very specific point may also occur as a result of a sudden tear in the muscle. In this case, the pain will be localised to a very distinct point. In both these cases, the pain develops suddenly. In other instances, muscle pain is the result of conditions that are longerlasting or chronic, and which may require medical consultation and diagnosis. These conditions include: • I nfections – flu, malaria, polio, roundworm, Lyme disease • Fibromyalgia – a condition in which there is body-wide pain and tender points in joints, muscles, and tendons •R habdomyolysis – breakdown of muscle cells by the body •P olymyalgia rheumatica – an autoimmune disease-causing muscle pain in the hip, shoulder or neck • L upus – an auto-immune disease with chronic, long term inflammation causing muscle pain •C ertain drugs can also cause muscle pain, including ACE inhibitors used for blood pressure treatments, statins used for cholesterol treatment, and cocaine. TREATMENT Treatment is dependent on the cause of the muscle pain. For exercise related muscle pain, rest, ice, and limiting of movements causing pain are usually sufficient. In cases where muscle pain is part of a broader spectrum of symptoms, treatment will be prescribed for the identified condition. Treatment will often involve anti-inflammatory medication, as well as massage and physical therapy.

Neck muscle spasm? Back muscle spasm? Acute muscle spasm?

• Improves painful muscle spasm, tenderness and increases range of motion1,2,3 • Relieves acute muscle spasm at day 4 of treatment1,2 • Diffucaps formulation maintains therapeutic levels over 24 hours2,4 • Well-tolerated with a low rate of reported somnolence2 • Convenient once-daily dosing5

Sustained efficacy for painful muscle spasm2,4,6 References: 1. Malanga GA, Ruoff GE, Weil AJ, et al. Cyclobenzaprine ER for muscle spasm associated with low back and neck pain: two randomized, double-blind, placebo-controlled studies of identical design. Curr Med Res & Opin 2009;25(5):1179-1196. 2. Weil AJ, Ruoff GE, Nalamachu S, et al. Efficacy and tolerability of cyclobenzaprine extended release for acute muscle spasm: A pooled analysis. Postgrad Med 2010;122(4):158-169. 3. Borenstein DG, Korn S. Efficacy of a low-dose regimen of cyclobenzaprine hydrochloride in acute skeletal muscle spasm: Results of two placebo-controlled trials. Clin Therapeutics 2003;25(4):1056-1073. 4. Ruoff GE. Once-daily cyclobenzaprine extended-release: A simple alternative to control muscle spasm. Clinical update. Family Practice News. Available from http://www.familypracticenews.com//fileadmin/content_pdf/fpn/ supplement_pdf/wxhpzdcj_FPNEWS_Supplement32.pdf Accessed 14 Mar 2016. 5. Darwish M, Chang S, Hellriegel ET. A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: A randomized, double-blind, two-period crossover study in healthy volunteers. Clin Therapeutics 2009;31(1):108-114. 6. MYPROCAM 15 and MYPROCAM 30 extended release capsules approved package insert, March 2014. S5 MYPROCAM 15 capsules. Each extended-release capsule contains cyclobenzaprine hydrochloride 15 mg. Reg.No. 44/17.3/0904 S5 MYPROCAM 30 capsules. Each extended-release capsule contains cyclobenzaprine hydrochloride 30 mg. Reg.No. 44/17.3/0905 For full prescribing information refer to the package insert approved by the medicines regulatory authority. 10270847 06/2016. Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021 South Africa. Tel. +27 11 635 0000. www.adcock.com.

PAIN FOCUS

Pain

nociceptive vs neuropathic Pain is a sensory and emotional experience with multiple causes to which people respond in multiple and individual ways (different pain thresholds). Pain is a natural and very important function of the human body.

HE INTERNATIONAL ASSOCIATION for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. CLASSIFICATION OF PAIN If we start with the concept of pain as a disease, then treatment begins with a pain diagnosis. Pain has been categorised in a variety of different ways, a particularly useful division is based on the kind of damage it causes: Tissue damage (nociceptive pain) Nerve damage (neuropathic pain) According to The American Journal of Managed Care (AJMC) “Nociceptive pain results from activity in neural pathways secondary to actual tissue damage or potentially tissue-damaging stimuli. Neuropathic pain is chronic pain that is initiated by nervous system lesions or dysfunction and can be maintained by a number of different mechanisms.” NOCICEPTIVE PAIN Nociceptive pain is the most common type of pain and is caused by the detection of noxious or potentially harmful stimuli by the nociceptors around the body. It represents the normal response to noxious insult or injury of tissues such as skin, muscles, visceral organs, joints, tendons, or bones. Dr Steven Richeimer (The Richeimer Pain Institute and Chief, Division of Pain Medicine, Keck School of Medicine, University of Southern California) gives the following examples of nociceptive pain: “sprains, bone fractures, burns, bumps, bruises, inflammation (from an infection or arthritic disorder), obstructions, and myofascial pain (which may indicate abnormal muscle stresses). “Nociceptors are the nerves which sense and respond to parts of the body which suffer from damage”, explains Richeimer. “They signal tissue irritation, impending injury, or actual injury. When activated, they transmit pain signals (via the peripheral nerves as well as the spinal cord) to the brain. The pain is typically well localised, constant, and often with an aching or throbbing quality. Visceral pain is the subtype of nociceptive pain that involves the internal organs. It tends to be episodic and poorly localised. “Nociceptive pain is usually time limited, meaning when the tissue damage heals, the pain typically resolves. (Arthritis is a notable exception in that it is not time limited.) Another characteristic of nociceptive pain is that it tends to respond well to treatment with opioids.”

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NEUROPATHIC PAIN “Neuropathic pain is the result of an injury or malfunction in the peripheral or central nervous system. The pain is often triggered by an injury, but this injury may or may not involve actual damage to the nervous system,” says Richeimer. Nerves can be infiltrated or compressed by tumours, strangulated by scar tissue, or inflamed by infection. The pain frequently has burning, lancinating, or electric shock qualities. Persistent allodynia, pain resulting from a nonpainful stimulus such as a light touch, is also a common characteristic of neuropathic pain. The pain may persist for months or years beyond the apparent healing of any damaged tissues. In this setting, pain signals no longer represent an alarm about ongoing or impending injury, instead the alarm system itself is malfunctioning. “Examples [of neuropathic pain] include post herpetic (or post-shingles) neuralgia, reflex sympathetic dystrophy/causalgia (nerve trauma), components of cancer pain, phantom limb pain, entrapment neuropathy (e.g., carpal tunnel syndrome), and peripheral neuropathy (widespread nerve damage). Among the many causes of peripheral neuropathy, diabetes is the most common, but the condition can also be caused by chronic alcohol use, exposure to other toxins (including many chemotherapies), vitamin deficiencies, and a large variety of other medical conditions–it is not unusual for the cause of the condition to go undiagnosed. “Neuropathic pain is frequently chronic, and tends to have a less robust response to treatment with opioids, but may respond well to other drugs such as anti-seizure and antidepressant medications. Usually, neuropathic problems are not fully reversible, but partial improvement is often possible with

proper treatment,” Richeimer concludes. Much neuropathic pain is chronic. Examples of pain caused by damaged nerves include: • Central pain syndrome • Complex regional pain syndrome • Diabetic peripheral neuropathic pain • Shingles and postherpetic neuralgia • Trigeminal neuralgia. PAIN INTENSITY The University of Wisconsin School of Medicine and Public Health (UWSMPH) says pain intensity can be broadly categorised as mild, moderate, and severe. “It is common to use a numeric scale to rate pain intensity where 0 = no pain and 10 is the worst pain imaginable.” • Mild: <4/10 • Moderate: 5/10 to 6/10 • Severe: >7/10 PAIN DURATION UWSMPH also emphasises the classification of pain based on duration: Acute pain: pain of less than 3 to 6 months duration Chronic pain: pain lasting for more than 3-6 months, or persisting beyond the course of an acute disease, or after tissue healing is complete. Acute-on-chronic pain: acute pain flare superimposed on underlying chronic pain. Scotland’s Pain Concern describes acute pain as the pain you get after you bang your knee, have an operation or a heart attack. “It lasts for a limited period of time and usually responds well to medication. “Chronic pain is pain which persists or recurs for more than three months. It is now recognised as a condition in its own right.” “Many acute pains are like an alarm telling us something is wrong,” explains

the British Pain Society. “Most minor ones are easy to treat; others may be a sign of something more serious. For example the pain of a broken leg will make us rest the leg until it heals. Here the pain is helping.” Chronic pain on the other hand serves no useful purpose. “The messages from the warning system linked to long-term conditions like arthritis or back pain are not needed – just annoying. Over time, it may affect what we can do, our ability to work, our sleep patterns. It can have a strong negative effect on our family and friends too.” GENES AND PAIN Genes also have a role to play in the story of pain, says Professor Ana Valdes (Associate Professor, Faculty of Medicine and Health Sciences at the University of Nottingham). Her research is helping to explain why some people develop conditions such as fibromyalgia, migraine or rheumatoid arthritis and others do not based on differences in our makeup at the molecular level. Even our psychological responses to pain are affected by differences in the nervous system. Valdes believes these more sophisticated approaches to pain offer hope of effective treatment in the future. TECHNIQUES THAT HELP WITH PAIN MANAGEMENT • deep breathing • relaxation • positive imagery • thought distraction • heat or cold compresses (or a combination of the two) • reducing stress in your life • remaining positive • exercise”.

lidocaine

TREATING PAIN BELOW THE SURFACE

N E Whic pain

neuro pa t in SA t rea t m ent Versatis® 5 % medicated plaster for neuropathic pain (PHN): • • • •

As effective as pregabalin1 Low risk of systemic side effects and better tolerated than pregabalin2,3 Effective as monotherapy or in combination with systemic drugs1 Unique targeted dual mode of action3,4

Works where it hurts

PHN – Post-herpetic neuralgia References: 1. Rehm S, Binder A, Baron R. Post-herpetic neuralgia: 5% lidocaine medicated plaster, pregabalin, or a combination of both? A randomized, open, clinical effectiveness study. Curr Med Res Opin 2010;26(7):1607–1619. 2. Baron R, Allegri M, Correa-Illanes G, et al. The 5% Lidocaine-Medicated Plaster: Its Inclusion in International Treatment Guidelines for Treating Localized Neuropathic Pain, and Clinical Evidence Supporting its Use. Pain Ther 2016;5:149–169. 3. Baron R, Mayoral V, Leijon G, et al. 5% lidocaine medicated plaster versus pregabalin in postherpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study. Curr Med Res Opin 2009;25(7):1663–1676. 4. Rowbotham MC, Davies PS, Verkempinck C, Galer BS. Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain 1996;65:39–44. S4 Versatis® 5 % medicated plaster. Each plaster contains 700 mg (5 % m/m) lidocaine in an aqueous adhesive base (50 mg lidocaine per gram adhesive base). Reg. No.: 43/3.2.3/0382. 14030

For full prescribing information please refer to the package insert approved by the Medicines Regulatory Authority. 2019021410122862 Adcock Ingram Limited. Reg. No. 1949/0343385/06. 1 New Road, Midrand, 1685. Private Bag X69, Bryanston, 2021, South Africa. Tel. +27 11 635 0000. www.adcock.com

PAIN FOCUS

CLINICAL PAIN

WHAT TO DO FOR

BACK PAIN?

Lower back pain is a prevalent cause of disability across the globe, affecting more than 460 million people.

“In fact, back pain affects most of us at some point in our lives,” says Dirk Malan, a physiotherapist at Mediclinic Bloemfontein.

INJURIES Sports injuries such as strained muscles, sprained ligaments, fractures, bulging or ruptured discs and even muscle spasms can all cause back pain. “Acute lower back pain, on the other hand, is usally as a result of injury to the tendons, muscles, ligaments, joints, or discs,” Malan explains. These are usally sportsrelated injuries, but they can also occur from everyday activities or overuse of a certain muscle or tendon. The pain is caused when inflammation is triggered by an injury. “Exercising when you have chronic back pain can help you feel better and prevent worsening of the back problem, but it’s very important to start slowly, gradually building up intensity and frequency,” Malan advises.

EXERCISE AND BACK HEALTH Sufferers of a bad back should opt for low-impact exercises such as yoga, pilates, swimming (especially back stroke), walking and cycling. Serena advises that you focus on a good mix of exercises that help stretch the back, such as those that target the hamstring, knee and chest regions, as well as exercises that strengthen your core, like bridges and planks. Abdominal exercise gained by leg lifts or mountain climbing are also effective. It’s best to avoid these exercises:

• High-impact aerobics • Weight-lifting • Sit-ups and crunches • Spinning with a rounded back • Repetitive jumping, burpees or back twisting Patients should also consult a physiotherapist to assess core strength before taking up longdistance running, sports-specific activities like football, and group exercises like CrossFit and Boot Camp.

SURGERY SHOULD BE A LAST RESORT Back injuries are common, especially among competitive athletes. Nearly one in three athletes playing professional or varsity-level sports experiences a back injury, new research finds. “Competitive players stress their lumbar [lower] spine for hundreds of hours a month, thereby predisposing themselves to specific injuries that should be recognised by health care practitioners,” said Dr Wellington Hsu, an orthopedic spine surgeon in Chicago, US. The human spine has 24 bones, or vertebrae. They’re stacked on top of each other, separated by flat, round cushioning disks. When people walk or run, these disks absorb shock, the authors explained. Athletes are at risk for problems involving their back bones and discs, particularly if they start intense training regimens when they are between 10 and 24 years old, the researchers noted. One common problem for these young athletes is known

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as symptomatic lumbar disk degeneration. People with this condition have deterioration in a disk, resulting in a smaller space between the bones of the spine. In extreme cases, this condition is treated surgically. But the review authors said there is little evidence supporting the success of this procedure among athletes. Elite athletes between 20 and 35 years old may be at greater risk for another painful back problem known as lumbar disk herniation, the researchers warned. This occurs when the soft center of a disk pushes through its exterior due to wear and tear, or a sudden injury. This occurs when a small connecting bone in the lower back breaks, which could cause a spinal bone to disconnect and slip forward. Others prone to lower back injuries are athletes of all ages who lift heavy weights without supervision or without lower back protection while training for extreme sports, the researchers added. The review appears in the Journal of the American Academy of Orthopedic Surgeons. Surgery should be a last resort for athletes with lower back issues, said Hsu. He pointed out that rehab success rates are high for back injuries. Nonsurgical treatment for pain may include medication and psychological counselling. Physical therapy can also help athletes gain flexibility and strengthen their core and back muscles. The medicines recommended most often are: • Acetaminophen and nonsteroidal anti-inflammatory drugs such as ibuprofen and naproxen.

Pain • Inflammation • Fever

In SA, the combination of orphenadrine and paracetamol is registered for the treatment of muscle spasms in skeletal muscles and for the symptomatic treatment of mild to moderate pain. Orphenadrine is a muscle relaxant that exerts its effect in the brain. Paracetamol is the analgesic of choice for mild to moderate pain and to reduce fever. It is suited for both adults and children and, as it does not cause stomach irritation, it is safe to use by those who suffer from peptic ulcers and those who cannot take aspirin. • Opiate pain relievers are very strong medicines that are sometimes tried to ease severe back pain that has not been controlled by other medicines. They are usually taken for only one to two weeks. • Antidepressants. Some of these medicines, such as amitriptyline and duloxetine, not only treat depression but also may help with chronic pain.

References available on request.

T LOOKR OOUUR

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SOUTH AFRICA’S #1 PRESCRIBED BRAND TO RELIEVE EVERYDAY PAINFUL MUSCULOSKELETAL SPASM1,2

• Muscle relaxants. These medicines can help when you get bad muscle spasms along with low back pain. Side effects, such as drowsiness, are common. The combination of orphenadrine and paracetamol is a muscle relaxant.

NEW K

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Gen-Payne® Capsules. Each capsule contains: codeine phosphate 10 mg; ibuprofen 200 mg; paracetamol 250 mg. Reg. No. 35/2.8/0046. For full prescribing information refer to the package insert approved by the medicines regulatory authority. Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021. Tel. + 27 11 635 0000. www.adcock.com 202008121051113

References: 1. Waldman HJ. J Pain Symptom Manage 1994; 9(7):434-441. 2. Impact Rx. Script Data – October 2017. Scheduling status: S2 Proprietary name (and dosage form): NORFLEX CO Tablets. Composition: Each tablet contains 35 mg Orphenadrine citrate and 450 mg Paracetamol. Pharmacological classification: A.2.9 (Other analgesics). Reference number: B 1098 [Act 101/1965]; Scheduling status: S2 Proprietary name (and dosage form): NORFLEX Tablets. Composition: Each tablet contains 100 mg Orphenadrine citrate. Pharmacological classification: Category: A.2.10 (Centrally active muscle relaxants). Reference number: H 1612. [Act 101/1965]. Name and business address of applicant: iNova Pharmaceuticals (Pty) Ltd. Reg. No.: 1952/001640/07. 15E Riley Road, Bedfordview. Tel. No.: 011 087 0000 www.inovapharma.co.za. For full prescribing information, refer to the package insert as approved by the MCC (Medicines Control Council). Further information is available on request from iNova Pharmaceuticals. IN2524/18.

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MEDICAL CHRONICLE | MARCH 2018 17

Neck muscle spasm? Back muscle spasm? Acute muscle spasm?

PAIN FOCUS

Pain in the gut The cause of abdominal problems can be hard to pinpoint. Sometimes serious and minor abdominal problems start with the same symptoms.

LMOST EVERYONE HAS pain in the abdomen at some point. Most of the time it’s not serious. That said the intensity of pain doesn’t always indicate the cause or reflect its severity. For example, while patients suffering from common gastritis may report severe pain, patients with early appendicitis or colon cancer (both potentially terminal) may present with little to no pain at all. TOP 3 CAUSES OF ABDOMINAL PAIN GASTROENTERITIS Commonly referred to as the stomach flu, gastroenteritis is a condition that causes irritation and inflammation of the stomach and intestines. An acute infectious syndrome, gastroenteritis is caused by a micro-organism ingested in contaminated food or water, or from other sources. The virus or bacterium affects the stomach lining and intestines, causing some or all of nausea, vomiting, diarrhoea, and abdominal cramps, and sometimes more general symptoms such as fever and headache. Many different viruses may cause gastroenteritis, some examples of which include: • Rotaviruses (particularly in winter). • Enteroviruses (more common in summer). • Adenoviruses, astroviruses, Norwalk virus,

14 MEDICAL CHRONICLE

and other caliciviruses. Gastroenteritis can also be caused by: Bacteria: common bacterial causes include Campylobacter, Shigella, Salmonella, or certain strains of Escherichia coli. Some bacteria produce toxins which cause “food poisoning”. Parasites (Giardia is one example). Certain medications. Toxins in plants (including mushrooms) or other foods (e.g. “red tide” in shellfish). IRRITABLE BOWEL SYNDROME Irritable bowel syndrome (IBS) or spastic colon is one of the most common gastrointestinal disorders. It has also been called spastic colitis, mucus colitis, or nervous colon syndrome. It tends to be a chronic disorder, and the symptoms can wax and wane over many years. Most people have such mild symptoms that they never seek medical help. The disease is a functional bowel disorder involving the large intestine. Common symptoms are abdominal pain, bloating, mucus in stools, and irregular bowel habits, such as alternating diarrhoea and constipation. The symptoms are related to abnormal muscle contractions in any part of the intestines. A spastic colon does not adversely affect longevity or lead to more serious diseases such as inflammatory bowel disease or

cancer. The symptoms of a spastic colon typically occur early in life and half of those affected experience the symptoms before they reach the age of 30. CONSTIPATION Constipation occurs when stools become hardened and difficult to pass. Some people may be concerned about the frequency of their bowel movements because they have been taught that healthy people should have a bowel movement every day. This is not true. People usually pass stools from three times a day to three times a week. If stools are soft and pass easily, they are not constipated. Constipation is commonly caused by a diet lacking in fibre and/or water. The cause of chronic constipation cannot always be identified, but the most significant factor appears to be the painful passing of a stool once constipation has already developed. The longer a bowel movement is resisted, the larger and harder the stool becomes, which may cause pain when it is passed. Children in particular may then withhold stools, which causes cramping. After some time, the child may be unable to resist the urge to have a bowel movement and will pass a large mass of faeces. This can be painful, as the child may have to “push hard” during the bowel movement. Passing the stool relieves the pressure until another mass of stool collects and the cycle repeats itself. Other causes of constipation include: • The voluntary delay of bowel movements: o Sometimes children resist the urge to have a bowel movement because they are too involved in play and will not take time to go to the bathroom. • Others may be anxious about defecating in a particular place, such as toilets away from home. • Delay may be part of a more general pattern of oppositional or anxious

behaviour. • In the case of young children, delay may be caused by stress related to toilet training. • Circumstances such as travelling that disrupt diet, and time and place of defecation. • Lack of exercise. • Medication. • Pain caused by haemorrhoids and anal fissures. • Laxative overuse. • Irritable bowel syndrome. • Diseases of the metabolism. • Diseases of the endocrine system: • Hypothyroidism. • Excessive amounts of calcium in the blood due to hyperparathyroidism. • Diseases of the nervous system, such as Hirschsprung’s disease or diseases affecting the whole nervous system such as spinal cord damage. • Chronic lead poisoning. SYMPTOMS • Constipation may occur with cramping and pain in the rectum from the strain of trying to pass dry, hardened stools. • Some bloating and nausea may occur. • Sometimes small amounts of bright red blood appear on the stool. This can be the result of anal fissures – slight tearing of the anal membrane as the stool is pushed through the anus – which make the passing of stools very painful. The fissures, which often appear when constipation is chronic, should heal when the constipation is controlled. • Appetite may be suppressed. • There may be decreased interest in usual activities. • Urination may be more frequent because of pressure on the bladder. In the case of chronic constipation, there may be involuntary release of urine (incontinence).

400 mg paracetamol

8 mg codeine phosphate

200 mg meprobamate

PAIN FOCUS

Adding a ‘green prescription’

to pain management

Pain, a complex and multifaceted experience, is the predominant symptom in the majority of patients with inflammatory arthritis (IA) and osteoarthritis (OA).

AIN, A COMPLEX and multifaceted experience, is the predominant symptom in the majority of patients with inflammatory arthritis (IA) and osteoarthritis (OA). Appropriate exercise and staying active is a key aim for all patients with OA. Apart from pathological processes (inflammation and tissue damage), various other individual factors influence pain such as illness beliefs, mood, avoidance behaviour, obesity, sleep disturbance, and the pattern of rest and activity throughout the day. The authors of the new European League Against Rheumatism (EULAR) recommendations for pain management in IA and OA, propose a stepped-care approach, which includes education and self-management support, one or more treatment options by a specialist if indicated or multidisciplinary treatment. The choice for a specific intervention is not only determined by effects on pain but also by effects on functioning, social participation and well-being. CORNERSTONE OF PAIN MANAGEMENT Pharmacological treatment is the cornerstone of pain management in IA and OA. It includes analgesics (e.g., paracetamol, codeine and other opiate-like drugs), oral or topical non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular injections with glucocorticoids, and occasionally also agents for neuropathic pain. TROPICAL TREATMENTS Tropical treatments should be considered for patients with localised pain who have contraindications to oral NSAID use. Topical capsaicin (0.025%): Topical capsaicin is reported to reduce pain by 25%-30% on average compared to placebo. Recommended for patients with OA who have not improved sufficiently with paracetamol and for whom oral NSAIDs are contraindicated. Topical NSAIDs: Include diclofenac and ibuprofen gels or sprays. Reported to reduce pain by approximately 30% on average compared to applications of a placebo. Significant improvements in symptoms can be expected within the first week of treatment. WEAK OPIOIDS FOR PATIENTS WITH ONGOING OR SEVERE SYMPTOMS Many patients with OA have flares and remissions, but overall their symptoms remain at the same intensity. Some patients experience a moderate to severe progression of symptoms, and therefore their pain management may need to be escalated. Guidelines recommend weak opioids, such as codeine, tapentadol or tramadol.

However, these should be reserved for use in patients who do not sufficiently improve, are unable to tolerate or have contraindications to paracetamol, topical treatments or oral NSAIDs. Stronger opioids may have small to moderate benefits, however, this may not be sufficient to balance the risks of side-effects such as falls, drowsiness, constipation and addiction. INTRA-ARTICULAR CORTICOSTEROID INJECTIONS MAY BE USEFUL FOR FLARES Intra-articular corticosteroid injections produce short-term reductions in pain (e.g. one month), but do not improve joint function or stiffness. They are therefore most likely to be useful for treating flares. A three-month period between injections is recommended. ORAL NSAIDs Oral NSAIDs reduce pain by 30%-44%, about double the effect of paracetamol.

Also associated with greater improvements in function and stiffness than paracetamol or placebo medicines. This treatment may be considered for patients with ongoing pain and discomfort despite non-pharmacological approaches and paracetamol use, or those with more severe symptoms at diagnosis, provided they do not have contraindications. Due to its side-effect profile, NSAIDs should be prescribed at the lowest effective dose for the shortest possible time. The decision as to which NSAID to use can be based on the patient’s response and preference, side-effects and comorbidities. The use of a proton pump inhibitor (PPI) for gastrointestinal (GI) protection in patients over the age of 65 years at increased risk of GI side-effects. Celecoxib has a lower risk of GI side-effects than non-selective NSAIDS, and this risk is even lower when prescribed with a PPI. PARACETAMOL Paracetamol is recommended as first-line

therapy. Patients with OA taking regular paracetamol at a dose of 4g/day (the recommended dose, unless malnourished, weigh under 50kg, are dehydrated or have a high alcohol intake) reported an average 18% reduction in pain and 15% improvement in function compared to patients taking placebo. ADD A ‘GREEN PRESCRIPTION’ Appropriate exercise and staying active is a key aim for all patients with OA. Consider writing a ‘green prescription’, which may help patients feel they are not just being given general lifestyle advice but are being offered specific evidencebased treatment. WEIGHT LOSS A reduction of 5%–10% of initial body weight can produce significant improvements in symptoms. Weight loss of about 10% results in symptom improvement comparable to the effect of joint replacement surgery. MEDICAL CHRONICLE 17

PAIN FOCUS| PAIN CLINICAL

A guide to

tapering opioids The US Health and Human Services (HHS) Working Group on Patient-Centered Reduction or Discontinuation of Long-term Opioid Analgesics developed a guide for clinicians on the appropriate dosage reduction or discontinuation of long-term opioid analgesics.

UDICIOUS OPIOID ANALGESIC prescribing can benefit individual patients as well as public health when opioid analgesic use is limited to situations where benefits are likely to outweigh risks. At the same time, opioid analgesic prescribing changes, such as dose escalation, dose reduction or discontinuation of long-term opioid analgesics, have potential to harm or put patients at risk if not made in a thoughtful, deliberative, collaborative, and measured manner. In each case the clinician should review the risks and benefits of the current therapy with the patient, and decide if tapering is appropriate based on individual circumstances. Whether or not opioids are tapered, safe and effective nonopioid treatments should be integrated into patients’ pain management plans based on an individualised assessment of benefits and risks considering the patient’s diagnosis, circumstances, and unique needs. Coordination across the healthcare team is critical. Clinicians have a responsibility to provide or arrange for coordinated management of patients’ pain and opioidrelated problems, and they should never abandon patients. Consider tapering to a reduced opioid dosage, or tapering and discontinuing opioid therapy, when: • Pain improves • The patient receives treatment expected to improve pain • The patient requests dosage reduction or discontinuation

• Pain and function are not meaningfully improved • The patient is receiving higher opioid doses without evidence of benefit from the higher dose • The patient has current evidence of opioid misuse • The patient experiences side effects that diminish quality of life or impair function • The patient experiences an overdose or other serious event (eg, hospitalisation, injury), or has warning signs for an impending event such as confusion, sedation, or slurred speech • The patient is receiving medications (eg, benzodiazepines) or has medical conditions (eg, lung disease, sleep apnoea, liver disease, kidney disease, fall risk, advanced age) that increase risk for adverse outcomes • The patient has been treated with opioids for a prolonged period (years), and current benefit-harm balance is unclear. Treat symptoms of opioid withdrawal If tapering is done gradually, withdrawal symptoms should be minimised and manageable. Expectation management is an important aspect of counselling patients through withdrawal. Significant opioid withdrawal symptoms may indicate a need to pause or slow the taper rate. Onset of withdrawal symptoms depends on the duration of action of the opioid medication used by the patient. Symptoms can begin as early as a few hours after the last medication dose or as long

18 MEDICAL CHRONICLE 18 NOVEMBER 2019 | MEDICAL CHRONICLE

as a few days, depending on the duration of action. Early withdrawal symptoms (eg, anxiety, restlessness, sweating, yawning, muscle aches, diarrhoea and cramping) usually resolve after 5-10 days but can take longer. RISKS OF RAPID OPIOID TAPER Opioids should not be tapered rapidly or discontinued suddenly due to the risks of significant opioid withdrawal. Risks of rapid tapering or sudden discontinuation of opioids in physically dependent patients include acute withdrawal symptoms, exacerbation of pain, serious psychological distress, and thoughts of suicide. Patients may seek other sources of opioids, potentially including illicit opioids, as a way to treat their pain or withdrawal symptoms. Unless there are indications of a life-threatening issue, such as warning signs of impending overdose, HHS does not recommend abrupt opioid dose reduction or discontinuation.

Some symptoms (eg, dysphoria, insomnia, irritability, increased pain) can take weeks to months to resolve. Shortterm oral medications can help manage withdrawal symptoms, especially when prescribing faster tapers. These include alpha-2 agonists for the management of

autonomic signs and symptoms (sweating, tachycardia), and symptomatic medications for muscle aches, insomnia, nausea, abdominal cramping, or diarrhoea. SUPPORT Provide behavioural health support. Make sure patients receive appropriate psychosocial support. Ask how you can support the patient. Acknowledge patient fears about tapering. While motives for tapering vary widely, fear is a common theme. Many patients fear stigma, withdrawal symptoms, pain, and/or abandonment. Tell patients “I know you can do this,” or “I’ll stick by you through this.” Make yourself or a team member available to the patient to provide support, if needed. Let patients know that while pain might get worse at first, many people have improved function without worse pain after tapering opioids. Follow up frequently. Successful tapering studies have used at least a weekly follow up. Watch closely for signs of anxiety, depression, suicidal ideation, and opioid use disorder and offer support or referral as needed. Collaborate with mental health providers and with other specialists as needed to optimise psychosocial support for anxiety related to the taper. REFERENCE HHS Guide for Clinicians on the Appropriate Dosage Reduction or Discontinuation of Long-Term Opioid Analgesics, September 2019. (U.S. Department of Health and Human Services).

PAIN FOCUS

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CPD

PAIN FOCUS PAIN

Osteoarthritis pain, joint function and QoL

Chronic diseases of the musculoskeletal system are among the most prevalent health hazards in the world's population.

According to the World Health Organization (WHO), an ageing society is one in which 7% of the population is ≥65 years old, while in an ‘aged society’ or ‘hyper aged society’ this proportion reaches 14% and 20%, respectively. Accommodating the ageing population is a global challenge and the real-world experience is becoming increasingly important. Knee osteoarthritis is a major public health issue related to age, characterised by progressive loss of articular cartilage resulting in pain,

functional impairment, disability and diminished patient's quality of life. About 10% of the population over 60 years old complain of this condition. In the US, about 37% of the population aged above 60 present a diagnosis of knee osteoarthritis. It is estimated that in 2025 the prevalence of knee osteoarthritis will increase by 40% due to the ageing of the world population. This data becomes even more alarming in Brazil, since the current Brazilian population over 60 years old is 19 million and it is estimated

that it will increase to 64 million by 2050.

RISK FACTORS

synovitis, osteophytosis, loss of joint space, bone remodelling and ultimately, it progresses to severe and irreversible joint destruction.

Some risk factors contribute to the appearance of the disease, such as gender, age, trauma, overuse and genetic conditions. The main tissues affected by osteoarthritis is the synovium, bone and hyaline cartilage. It is a joint disease that begins with cartilage degeneration and gradually affects periarticular soft tissues and the subchondral bone, producing chronic inflammation with

Patients with knee osteoarthritis tend to increase their physical limitations, pain and functionality restriction with disease progression. So, these individuals suffer from progressive, increased impact on their activities of daily living, which leads to losses in work, leisure, social life, and sleep quality, leading also to important

QOL

Generic Etoricoxib from Adcock Ingram. The name you’ve come to trust. S3 Adco-Etoricoxib 60 mg. Each tablet contains 60 mg etoricoxib. Reg. No.: 50/3.1/0301. S3 Adco-Etoricoxib 90 mg. Each tablet contains 90 mg etoricoxib. Reg. No.: 50/3.1/0302. S3 Adco-Etoricoxib 120 mg. Each tablet contains 120 mg etoricoxib. Reg. No.: 50/3.1/0303. For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority. 201808011091417 Adcock Ingram Limited. Reg. No. 1949/034385/06. 1 New Road, Midrand, 1685. Private Bag X69, Bryanston, 2021. Tel. +27 11 635 0000. www.adcock.com

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38 2018 | MEDICAL CHRONICLE 20 NOVEMBER MEDICAL CHRONICLE

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CPD decrease in their quality of life. An important outcome to be evaluated in patients with knee osteoarthritis is the quality of life of these individuals. Normally, quality of life is evaluated as the impact the disease causes to the subject. According to the World Health Organization (WHO), ‘quality of life’ is described as an individual's perception of his/ her position in life in the context of the culture and value systems in which he lives and in relation to his goals, expectations, standards and concerns. Individuals with osteoarthritis have a low perception of their quality of life in the domains functional capacity, functional limitations and pain. There is a strong association between low educational level and low quality of life. This finding was also related to the fact that individuals with low education are engaged in physical work activities and higher impacts.

index were lower after treatment (pain, p ≤0.001; disability, p = 0.020). BPISF showed a significant improvement in joint function when walking and performing normal work (walking, p = 0.021; normal work, p = 0.030). SF36 scores improved for seven out of 11 items after etoricoxib treatment (#1, p = 0.032; #4, p = 0.026; #5, p = 0.017; #6, p = 0.008; #7, p = 0.009; #8, p = 0.013; and #10, p = 0.038). EQ-5D showed a significant improvement in visual analogue scale scores (p = 0.036). TSQM results demonstrated a higher

PAIN FOCUS PAIN

patient perception of overall satisfaction. No adverse events were reported. Pain relief, joint function, quality of life, and treatment satisfaction improved significantly in elderly patients with OA after etoricoxib administration. The study showed that after switching to etoricoxib, the pain, joint function, quality of life, and treatment satisfaction improved significantly in extremely elderly patients with OA. On average, both pain and disability scores decreased as determined using the WOMAC index and BPI-SF. The TSQM

results showed a higher perception of overall satisfaction with the treatment among the patients. The quality of life scores measured by the SF36 and EQ5D VAS also significantly improved after switching to etoricoxib. No adverse events were reported during the four-week treatment or twomonth follow-up. This study is believed to be the first analysis of the efficacy of etoricoxib in treating OA in the extreme elderly population. The extreme elderly are a growing population, often not adequately represented in

POWER BEYOND PAIN

OA IMPACT ON PATIENTS • People with OA are at risk of falls due to pain, joint instability, altered gait, ageing and medication use • Patients often experience depression and anxiety, exacerbated by a lack of self-efficacy and catastrophisation (focusing on negative aspects) • Between 31% and 41% of people with OA experience anxiety, compared with around 17% for all types of anxiety in the older adult general population.

ETORICOXIB

We’ve been working hard to give patients access to quality and affordable products - even before 1998, when the first selective COX-2 inhibitor was launched1,2 Generic Etoricoxib from Adcock Ingram. The name you’ve come to trust.

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References: 1. Hawkey CJ. COX-2 chronology. Gut 2005;54:1509–1514. doi: 10.1136/gut.2005.065003. 2. Adcock Ingram. Our Heritage. Available at: http://www.adcockingram.co.za/AboutUs/Heritage (last accessed 26/04/2018). CINGULATE 12981

Etoricoxib is a selective cyclooxygenase-2 inhibitor, with a lower risk of gastrointestinal toxicity compared to traditional nonsteroidal anti-inflammatory drugs (NSAIDs). The authors evaluated the effectiveness and tolerability of etoricoxib in extremely elderly patients with chronic pain due to osteoarthritis (OA). A prospective, single-centre, single-arm study was conducted, enrolling 19 extremely elderly men with OA (mean age 85, range 79-96 years), who responded inadequately to NSAIDs or other analgesics. Patients were switched to etoricoxib, 60mg once daily for four weeks, without prior medication washout. Data were recorded before and after etoricoxib treatment. The primary endpoint was improvement in pain, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) after the four-week treatment. Other endpoints included the Brief Pain Inventory Short Form (BPI-SF), Treatment Satisfaction Questionnaire for Medication (TSQM), Short Form 36 (SF36), and European Quality of Life-5 Dimensions (EQ-5D). Safety and tolerability were assessed by collecting adverse events data. Pain and disability scores measured by WOMAC

S3 Adco-Etoricoxib 60 mg. Each tablet contains 60 mg etoricoxib. Reg. No.: 50/3.1/0301. S3 Adco-Etoricoxib 90 mg. Each tablet contains 90 mg etoricoxib. Reg. No.: 50/3.1/0302. S3 Adco-Etoricoxib 120 mg. Each tablet contains 120 mg etoricoxib. Reg. No.: 50/3.1/0303.

For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority. 201808011091427 S3 Ingram Limited. Reg. No. 1949/034385/06. 1 New Road, Midrand, 1685. Private Bag X69, Bryanston, 2021. Adcock Tel. +27 11 635 0000. www.adcock.com

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MEDICAL CHRONICLE 21 MEDICAL CHRONICLE | NOVEMBER 2018 39

PAIN FOCUS

CPD

PAIN

Significant effort and investment have been made in the development of novel therapeutics for managing pain

epidemiological studies. In a number of trials, the clinical efficacy of etoricoxib in the symptomatic treatment of OA pain has been well documented. The efficacy of etoricoxib treatment of six-12 weeks was significantly higher than placebo in improving pain symptoms in patients with OA, and as effective as diclofenac, ibuprofen, naproxen, or celecoxib. Similar to these findings, an analysis of the extreme elderly in a paired design showed reductions in scores for WOMAC pain and physical function and patient’s global assessment that were equivalent for 30mg etoricoxib once daily vs 800mg ibuprofen three times daily, as well as for 60mg etoricoxib once daily vs 50mg diclofenac three times daily and vs 500mg naproxen twice daily, and met the criteria for noninferiority for etoricoxib vs celecoxib. Furthermore, efficacy with etoricoxib was maintained for up to 4.5 years in extension studies. Also, etoricoxib was generally well tolerated in clinical trials of patients with OA and other types of arthritis. The researchers observed

INSTRUCTIONS:

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an improvement of the quality of life in extremely elderly patients, with the given treatment dose and period that was shorter compared to the other trials. In addition to the improvement of the quality of life, drug safety is another important issue. Regarding the risk of thrombotic cardiovascular (CV) events, the multinational etoricoxib and diclofenac arthritis long-term programme, including a pooled analysis of >34 000 patients with OA or rheumatoid arthritis, showed that, in terms of the overall rate of arterial and venous thrombotic CV events, etoricoxib was non-inferior to diclofenac. Similarly, in a pooled analysis of 12 trials no difference between etoricoxib and nonnaproxen NSAIDs was evident regarding thrombotic events. In addition, MI resulting from etoricoxib was reported in only one trial (relative risk 1.58, 95% confidence interval 0.06 to 38.66). On the other hand, Savage suggested that, due to their thrombotic potential, COX-2 inhibitors are contraindicated in patients with ischemic heart disease or

stroke as well as in patients that are at high risk of developing those conditions, which was also suggested in another study. Currently, there are several families of drugs clinically recognised as pain therapeutics, which have varying degrees of efficacy and adverse events, often limiting their utility. The management of inflammatory conditions typically includes NSAIDs, inhibitors of COXs (COX-1 and/or COX2), and opiates. Significant effort and investment have been made in the development of novel therapeutics for managing pain, including COX inhibiting nitric oxide donors and the dual COX/ lipoxygenase (LOX) inhibitor, licofelone. Initial results suggest that those therapies may be more tolerable compared to NSAIDs and selective COX-2 inhibitors. Future clinical trials evaluating the efficacy of new therapeutics in comparison with etoricoxib are warranted, especially in the frail and extremely elderly patients who are at increased risk for side effects and reduced drug tolerance. Other

assistance and therapies should be considered, in addition to pharmacologic treatment, in an effort to further aid the patients in this age group.

CONCLUSION OA is a disease commonly associated with pain, but it is much more complex than that for many people. Pain itself is complex, making it difficult to treat, and people with OA also experience anxiety, depression, sleep disturbance, social isolation and financial worries. Traits that can increase the risks of negative outcomes for people with OA include catastrophisation, low self-efficacy and pessimism. OA is a complex disease involving a multitude of interacting factors that can have an unpredictable and negative impact on health and quality of life. Reference

Huang W, Tso T. Etoricoxib improves osteoarthritis pain relief, joint function, and quality of life in the extreme elderly. Bosn J Basic Med Sci. 2018 Feb; 18(1):87–94. doi:10.17305/bjbms.2017.2214.

1. Go to www.medicalacademic.co.za 2. Click the tab labelled ‘CPD Portal’ on the far right tab near the top of the page. 3. Select the relevant questionnaire from the list and complete the form. Disclaimer: Please note that this article might only be a section of a larger CPD programme. Kindly visit www.medicalacademic.co.za to complete the full questionnaire. This CPD article is valid for a year from the date of publication.

Dysmenorrhoea:

PAIN FOCUS

Prevalent and undertreated

Dysmenorrhoea interferes with the daily life of an estimated one in five women. And yet, there’s remarkably little research into the condition, say experts. John Guillebaud, Professor of Reproductive Health at University College London.

YSMENORRHOEA INTERFERES WITH the daily life of an estimated one in five women. And yet, there’s remarkably little research into the condition, say experts. John Guillebaud, Professor of Reproductive Health at University College London, has recently been reported as describing the cramping pain as ‘almost as bad as having a heart attack’. It’s estimated that while 20% of women have the primary dysmenorrhea, around 10% of ovulating women in the US have endometriosis, and it takes on average 10 years to get an accurate diagnosis. The prevalence of dysmenorrhoea is difficult to determine because of different definitions of the condition – prevalence estimates vary from 45%- 95%. However, dysmenorrhoea seems to be the most common gynaecological condition in women regardless of age and nationality. Absenteeism from work and school as a result of dysmenorrhoea is common (13%51% of women have been absent at least once and 5%-14% are often absent owing to the severity of symptoms). Dysmenorrhoea, especially when it is severe, is associated with a restriction of activity and absence from school or work. Yet, despite this substantial effect on their quality of life and general wellbeing, few women with dysmenorrhoea seek treatment as they believe it would not help. There are two main causes of period pain: Primary and secondary dysmenorrhea. The former is simply painful periods, with no certain medical explanation, that tends to affect women as soon as they start menstruation. But the distinction between the two conditions is not clear-cut, as many women suffering dysmenorrhea may have undiagnosed endometriosis. Primary dysmenorrhoea is menstrual pain without organic disease, and secondary dysmenorrhoea is menstrual pain associated with an identifiable disease. Common

causes of secondary dysmenorrhoea include endometriosis, fibroids (myomas), adenomyosis, endometrial polyps, pelvic inflammatory disease, and the use of an intrauterine contraceptive device. Meanwhile, the medical reasons for primary dysmenorrhea are largely unknown. Some believe the pain is partly caused by uterus cramps, while others say a combination of sensory processing, local uterine inflammation, and uterine blood flow issues are also factors. Why some people suffer more than others is not well understood. In a study conducted in 2015 (Kural, Noor, et al), the highest number of girls (42%) having dysmenorrhoea was observed at the age of 19-20 years. More than two thirds of the girls (70%) described their dysmenorrhoea as moderate to severe. Pain was found to be an extremely subjective symptom and it was

difficult to quantify pain. Researchers have, therefore, found out a way to measure pain by various scoring systems like the visual analogue scale. In this study, it was revealed that 29%, 36% and 34% of girls had mild, moderate and severe pain, respectively. This indicates dysmenorrhea is still an important public health problem which may have a negative impact on health, social environment, work and psychological status. Some of the studies have determined that the prevalence of dysmenorrhea decreases with increasing age, indicating that primary dysmenorrhoea peaks in late adolescent and then the incidence falls with increasing age. The present study also showed more numbers of girls with dysmenorrhoea at 19-20 and then the number falls. However, the difference was not significant (p >0.05) data was not reported across age groups. Several studies have shown a significant

association between early age at menarche and dysmenorrhea. The underlying reason could be the fact that girls who attained menarche early have longer exposure to uterine prostaglandins leading to higher prevalence of dysmenorrhoea. However, since majority of girls were in reference category of 1214 years for age of menarche, there was no significant difference in the mean age of menarche between the two groups (presence and absence of dysmenorrhoea). The data differs from other studies where age of menarche is an important factor. One of the reasons could be less number of girls below 12 and above 15 years for age at menarche. These findings are on par with results observed by Pawlowski et al., who did not find any difference in the ages of menarche between dysmenorrheic and non dysmenorrheic girls..

When they call for the relief of menstrual pain, prescribe MYPAID. Although mild pain is common during menstrual cycle, some women experience pain severe enough to keep them from their normal activities.1 Each capsule of Mypaid contains ibuprofen and paracetamol that ensures the relief of pain.

S2 Mypaid Capsules. Each capsule contains ibuprofen 200 mg; paracetamol 250 mg. Reg. No. 27/2.8/0289. For full prescribing information refer to the package insert approved by the medicines regulatory authority. 202009141057189 Adcock Ingram Limited. Reg. No. 1949/034385/06 Private Bag X69, Brynston, 2021, South Africa Telephone +27 11 635 000 www.adcock.com

INDICATIONS: capsules are indicated for the relief of headache from muscle-skeletal origin, feverishness, muscular, menstrual and dental pain; INGREDIANTS: Each capsule contains Ibuprofen 200mg, Paracetamol 250mg. Sugar Free. DOSAGE: For adults and children over 12 years. Two capsules every four hours, but not more than six capsules in twenty-four hours. Capsules to be taken with food or after meals with sufficient water. References: 1. Capital Women's Care. Pelvic Pain. http://www.cwcare.net/services/gynecological-challenges/pelvic-pain. (Accessed 20 October 2020)

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DISINTEGRATE

PAIN Pain • Inflammation • Fever

Postoperative pain

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a psychological assessment

An effective postoperative management is not a standardised regime and is rather tailored to the needs of the individual patient

ANAGEMENT OF POSTOPERATIVE pain relieves suffering and leads to earlier mobilisation, a shortened hospital stay, reduced hospital costs, and increased patient satisfaction. An effective postoperative management is not a standardised regime and is rather tailored to the needs of the individual patient, taking into account medical, psychological, and physical condition; age; level of fear or anxiety; surgical procedure; personal preference; and response to therapeutic agents given. Dr Sean Chetty, Deputy Head of the Department of Anaesthesiology and Critical Care at the University of Stellenbosch, and an executive committee member of the Pain SA society, says that postoperative pain management should be individualised, personalised and focussed on the psychological state of the patient prior, during and after surgery. Dr Milton Raff, past chairman of the Pain Committee of the World Federation of Societies of Anaesthesiologists (WFSA), in the South African Society of Anaesthesiologists (SASA) 2016 guideline, explains that the WFSA and the International Association for the Study of Pain (IASP) have both identified the fact that pain is badly managed in all parts of the world, but that attention needs to be given to pain management in developing countries. “It has become evident that acute pain management must be the starting point for educational initiatives. Chronic pain can only be addressed when the management of acute pain is effected. Anaesthesiologists predominantly treat acute postoperative pain. Records of their success have been documented, but it has been demonstrated in only a few studies that alleviating this form of pain is effective. The classic Apfelbaum study of 2003 revealed that in the period 1995–2003, very little progress was made in managing pain. “Approximately 80% of all surgical patients experienced moderate to extreme pain following their surgery. Reports from the recent European PAIN OUT Symposium 2014 were also not encouraging as it was revealed that 40% of patients experienced severe postoperative pain, and almost 50% of patients

wished that they had received better pain therapy. “Unrelieved pain has other consequences besides patient satisfaction. Adverse physiological and psychological effects may result from unrelieved severe acute pain. It can be concluded that there are physiological, psychological and economic reasons to ensure that patients receive effective acute pain therapy.”

“Postoperative pain is considered a form of acute pain due to surgical trauma with an inflammatory reaction and initiation of an afferent neuronal barrage. It is a combined constellation of several unpleasant sensory, emotional and mental experience precipitated by the surgical trauma and associated with autonomic, endocrinemetabolic, physiological and behavioural responses.

DEFINITION OF PAIN The Taxonomy Committee of International Association for the study of Pain (IASP) defines pain as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage’. According to a study, The Clinical Aspects of Acute Post-operative Pain Management & its Assessment, by Anuj Gupta et al,

THE IMPACT OF PERIOPERATIVE CARE The practice of modern anesthesiology extends from pre-operative period to the intra-operative period, and then into the post-operative period. The main purpose of perioperative pain control is providing an adequate comfort level and reduced side effects for patients. Effective postoperative analgesia improves patients’ outcome as observed by a decrease in side effects, and reduced incidences of postoperative pain. “Pain is a highly subjective experience, and no two patients will experience pain in exactly the same manner,” explains Chetty. “Genetics, past experiences and emotional state will determine the manner in which a patient will experience pain, as well as the pain threshold of an individual. The perioperative period is therefore crucial in establishing a patients specific intraoperative and postoperative pain management needs.” THE PHYSIOLOGY OF ACUTE PAIN Pain is a complex interaction of sensory, emotional and behavioral factors. There are no pain pathways, only nociceptive pathways. Nociception is modulated at the level of the spinal cord and interpreted by the cortex, resulting in varying degrees of discomfort and pain. Acute pain is defined as pain of short and limited duration. The pain relates to an identifiable cause (trauma, surgery or inflammation). Acute and chronic pain represent a continuum of a process where inflammatory

neuropathic visceral and somatic pain plays a role. The central nervous system (CNS) is not a hard-wired system. It allows for peripheral, central, intracellular and synaptic modifications. Acute pain can result in longterm changes and a subsequently modified response to sensory input (neuroplasticity). “Essentially the primary role of managing pain in the postoperative period is to consistently monitor and manage the level of pain a patient will experience during the acute period which will typically last between 24 to 48 hours post-surgery. After major surgery, the management of postoperative pain can typically last a week, says Chetty. TYPES OF PAIN The Pain Management Handbook: A Concise Guide to Diagnosis and Treatment, edited by M. Eric Gershwin, Maurice E. Hamilton defines pain as: Nociceptive Pain is the signal of tissue irritation, impending injury, or actual injury. Nociceptors in the affected area are activated and then transmit signals via the peripheral nerves and the spinal cord to the brain, activated the complex spinal reflexes (withdrawal), followed by perception, cognitive and affective responses, and possibly voluntary action. Nociceptive pain is usually time limited–arthritis is a notable exception–and tends to respond well to treatment with opioids. Neuropathic Pain is the result of the nervous system injury or malfunction, either in the peripheral or in the central nervous system. The pain may persist for months or years beyond the apparent healing of any damaged tissues. Neuropathic pain is frequently chronic, and tends to have a less robust response to treatment with opioids. Psychogenic Pain due to the psychological factors leading to an exaggerated or histrionic presentation of the pain problem. Mixed Category Pain is caused by a complex mixture of nociceptive and neuropathic factors. An initial nervous system dysfunction or injury may trigger the neural release of inflammatory mediators and subsequent neurogenic inflammation. For example, migraine headaches, myofascial pain. Postoperative pain can be divided into acute pain and chronic pain: • Acute pain is experienced immediately after surgery (up to seven days) and pain which lasts more than three months after the injury is considered to be chronic pain. Acute and chronic pain can arise from cutaneous, deep somatic or visceral structures. • Acute pain plays some useful positive role such as to provide a warming of tissue

MEDICAL CHRONICLE 25

PAIN FOCUS damage and inducing immobilisation to allow appropriate healing. But, pain has some short term negative effects such as sleep disturbance, cardiovascular side effects, increase oxygen consumption, impaired bowel movement, delays mobilisation and promotes thromboembolism. ADVERSE EFFECTS OF PAIN The aim of adequate pain management is to provide pain relief as a humane measure, as well as to minimise the multi-system deleterious effects caused by the stress response. A catabolic state, sympathetic stimulation and immuno-suppression are hallmarks of the stress response. The psychological effects can create a vicious cycle, maintaining the negative effects. The endocrine system changes result in a catabolic state, increased adrenocorticotropic hormone, cortisol, antidiuretic hormone, cathecolamines, angiotensin II, interleukin (IL)-1 and IL-6, and tumour necrosis factor (Table 3). Sympathetic stimulation results in an increased heart rate and blood pressure, increasing the risk of myocardial ischaemia. Pain limits coughing and decreases functional residual capacity, which, in turn increases the risk of atelectasis and pulmonary infection. Decreased mobility results in an increased risk of deep vein thrombosis. Anxiety, helplessness, loss of control, an inability to interact and sleep deprivation all contribute to psychological disturbances, which can increase the risk of persistent pain developing. MEASUREMENT AND ASSESSMENT OF PAIN According to Wells N, Pasero C, McCaffery M. Improving the Quality of Care Through Pain Assessment and Management, “Pain assessment is recognised by virtually all of the pain guidelines as a crucial step in providing good pain management. The foundation of the pain assessment is the patient’s self-report of pain, but most patients lack the ability to discuss pain in a clinically meaningful way.” For that reason, a variety of tools have been introduced to help patients and clinicians ‘speak the same language’ about the pain. VERBAL DESCRIPTOR SCALE The verbal descriptor scale (VDS) involves setting up five specific terms to describe pain; at the extremes are ‘no pain’ and ‘worst pain possible‘. In addition to those two poles, the patient may select ‘mild’, ‘moderate‘, or ‘severe’ pain. Patients should be instructed to use only one of these five terms, and it is not uncommon in practice for patients to try to seek middle ground (‘mild to moderate’ or ‘moderate to severe’). VISUAL ANALOG SCALE The visual analog scale (VAS) involves a straight line of 10cm with tick marks, starting with 0 and indicating each centimeter; smaller lines may indicate millimeters. The patient is instructed that 0 indicates no pain and 10cm indicates the worst pain possible. The patient is then 26 MEDICAL CHRONICLE

asked to indicate on the line ‘how much’ pain he or she is experiencing. As a general rule, pain ≥3 cm demands treatment; pain ≥6 cm should be considered severe. NUMERICAL RATING SCALE The numerical rating scale works on a similar principle as the VAS, but instead of pinpointing the pain level on a straight line, the patient merely selects the number from 0 to 10 to describe his or her pain. Other pain assessment tools All of these pain assessment tools are easy to deploy and interpret. Other pain scales exist as well, such as the Red Wedge Scale and the Box Scale. A clinical practice should use only one assessment tool and use it consistently so that pain assessment results can be meaningfully compared and evaluated. Adjusting treatment according to the intensity of pain The World Health Organisation recommends a treatment stepladder, based on the severity of the pain, available drugs and patient condition, to be utilised. TREATMENT GUIDELINES 1.1 General information on opiods: Classification of opiods Opioid agonists Opioid dualists: Both antagonism and agonism. (Theoretically, the side-effects should cancel one another out) Opioid antagonists Atypical opioids SIDE-EFFECTS OF OPIODS Respiratory depression, sedation, nausea and vomiting, pruritis, constipation and tolerance. 1.2. General information on paracetamol The following information is important with regard to paracetamol: • Very safe drug when used in appropriate doses • Caution should be exercised in patients with liver failure • An excessive dosage may cause irreversible liver failure • Use with caution or decrease the dose if there is: acute liver disease, alcoholrelated liver disease, glucose-6-phosphate dehydrogenase deficiency. 1.3. General information on NSAIDS: Nonsteroidal anti-inflammatory drugs (for mild to moderate pain relief) • Nonsteroidal anti-inflammatory drugs (nsaids) can be classified into: • Cyclo-oxygenase (COX-1 and 2) inhibitors • Selective COX-2 inhibitors • Specific COX-2 inhibitors. Side-effects include the following: • Renal damage, especially if there is prior renal impairment or if the patient is hypovolaemic • Platelet impairment • Gastric erosions and haemorrhage • Possible poor wound healing (a concern of surgeons) • Asthma, which may be exacerbated in some patients. Parenteral administration applies to the following:

• Ketorolac • Lornoxicam • Parecoxib 1.4. Approach to oral combination analgesics A combination of the oral drugs are used extensively in South Africa. The rationale to combine drugs is to reduce the dose of each drug, therefore improving the sideeffect profile. “However, it is important that practitioners are aware of the components in combination drugs,” says Chetty. 1.5 Local anaesthetics Local anaesthetics are either short or long acting. Lignocaine is an example of a short-acting anaesthetic, and bupivacaine, ropivacaine and L-bupivacaine are examples of long-acting anaesthetics. When administering a local anaesthetic, it is important to be aware of the following side-effects: • The effects of a toxic dose • Cardiotoxicity • Neurotoxicity According to the International Association for the Study of Pain (IASP), “Decades of research have established that acute pain after surgery has a distinct pathophysiology that reflects peripheral and central sensitisation as well as humoral factors contributing to pain at rest and during movement. This can impair functionality and often culminates in delayed recovery.” Nociceptor activation, sensitisation, and hyperalgesia: • Surgical tissue trauma leads to nociceptor activation and sensitisation. As a result, individuals suffer ongoing pain at rest and increased responses to stimuli at the site of injury (primary hyperalgesia). • Different surgical procedures (including debridement for acute burn care) involve distinct organs and specific tissue within and adjacent to them, creating a variety of patterns of nociceptor sensitisation and differences in the quality, location, and intensity of postoperative pain. • Mediators released locally and systemically during and after surgery that contribute to nociceptor sensitisation include: prostaglandins, interleukins, cytokines and neurotrophins (e.g. nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), neurotrophin (NT)-3, NT-5, and brain-derived neurotrophic factor (BDNF)). • Decreased tissue pH and oxygen tension, and increased lactate concentration, persist at the surgical site for several days. These responses may contribute to peripheral sensitisation (e.g., muscle C-fibers) and spontaneous pain behaviour following an incision. Acid-sensing ion channels (e.g. ASIC3) likely transduce this ischemic-like signal. • Peripheral neutrophilic granulocytes (NGs) contribute to peripheral sensitisation and pain after surgical incision [3, 18]. Endogenous CD14+ monocyte responses (e.g., via the TLR4 signaling pathway) are associated with differences in the time course of postsurgical pain. • Nerves may be injured during surgery

and hence discharge spontaneously. Spontaneous action potentials in damaged nerves may account for qualitative features of neuropathic pain that may be present early in the postoperative period and can evolve into chronic neuropathic pain. Central sensitisation during acute postoperative pain: • Noxious input during and after surgery can enhance the responses of nociceptive neurons in the CNS (central sensitisation) thereby amplifying pain intensity. • The magnitude of central sensitisation depends on many factors, including the location of the operative site and the extent of the injury. α • amino-3-hydroxy-5-methyl-4isoxazolepropionic acid (AMPA)-receptor mediated spinal sensitisation contributes to pain and hyperalgesia after incision. • Phosphorylation of the AMPA receptor GluR1 subunit at Serine-831 via protein kinase C gamma (PKC), but not other conventional PKC isoforms (PKCα, βI and βII), leads to an increase trafficking of Ca2+ permeable AMPA receptors in theneuronal plasma membrane. • GluR1 is upregulated in the spinal cord ipsilateral to an incision via stargazin, a transmembrane AMPA receptor regulatory protein. • Other molecules involved in central sensitis ation after surgical incision involve phosphorylated extracellular signal-regulated kinases (ERK) 1/2, BDNF, Tumor necrosis factor) TNF, iNOS, mitogen-activated protein kinase phosphatase (MKP)3, monoamine oxidase (MAO) B, toll-like receptor (TLR) 4 receptor and cyclooxygenase (COX) 2 (among others). • Spinal inhibitory mechanisms may be able to prevent central sensitisation after surgery, for example via spinal -adrenoceptors, -Aminobutyric acid (GABA) receptors, or enhanced Glutamate transporters, among other mechanisms. • Opioids modulate central sensitisation in complex ways. Some in-vitro studies indicate that opioids can inhibit sensitisation of nociceptive pain pathways. • Clinical studies suggest that opioids actually amplify pain transmission one mechanism may be, for example, ketamine-sensitive phosphorylation of spinal NMDA receptors (NR2B at Tyr1472).

REFERENCES Clinical aspects of acute post-operative pain management & its assessment, Anuj Gupta, Kirtipak Kaur, Sheeshpal Sharma, Shubham Goyal, Saahil Arora and R.S. Murthy South African Societyof Anaesthesiologists Sedation Guidelines Chaturvedi S, Charturvedi A. Postoperative pain and its management. Indian J Crit Care Med 2007; 11:204-11 Clinical aspects of acute post-operative pain management & its assessment, Anuj Gupta, Kirtipal Kaur, Sheeshpal Sharma, Shubham Goyal, Saahil Arora, R.S.R Murthy, J Adv Pharm Technol Res. 2010 Apr-Jun; 1(2): 97–108. South African Society of Anaesthesiologists (SASA) Guideline 2015 Wells N, Pasero C, McCaffery M. Improving the Quality of Care Through Pain Assessment and Management.

PAIN FOCUS

Etoricoxib most cost-effective initial

NSAID treatment

NSAIDs are the mainstay treatment of osteoarthritis and rheumatoid arthritis, two of the leading causes of morbidity and disability worldwide.

STEOARTHRITIS (OA) and rheumatoid arthritis (RA) are leading causes of morbidity and disability worldwide. The main aims of treatment are to control pain, improve function and reduce disability. NSAIDs are the mainstay of chronic pain management for these diseases. Recent studies have proven that etoricoxib is the most cost-effective initial NSAID treatment According to Croom et al musculoskeletal diseases are a major cause of disability and disease worldwide. OA is particularly common, affecting 10% of men and 18% of women above the age of 60 years. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of chronic pain management in these diseases. NSAIDs have been associated with gastrointestinal adverse events (GAEs) and an increased risk of thrombotic cardiovascular (CV) events in placebo-controlled trials. Most guidelines recommend that NSAIDs should be prescribed at the lowest dose for the shortest duration of time. However, newer NSAIDs such as cyclo-oxygenase (COX-2) inhibitors has been shown to have a lower risk of gastrointestinal toxicity compared to traditional NSAIDs, according to Huang and Tso. Etoricoxib, a COX-2 inhibitor, is one of the new kids on the block. Etoricoxib was approved by the Medicines Control Council in September 2017. Etoricoxib is indicated for the short-term treatment of acute gouty arthritis, acute pain, primary dysmenorrhea and moderate to severe acute postoperative dental surgery pain. For chronic long-term pain relief, etoricoxib is indicated for OA, RA and ankylosing spondylitis (AS). EFFICACY, SAFETY AND TOLERABILITY OF ETORICOXIB Leung et al evaluated the efficacy of 12 weeks of treatment with etoricoxib, in patients with OA of the knee or hip. Eligible patients were treated with etoricoxib 60mg once daily, naproxen 500mg twice daily or placebo. Western Ontario McMaster’s Osteoarthritis Index (WOMAC) pain and physical function subscales and patient’s global assessment of disease status were primary endpoints. Key secondary and other endpoints were patient’s and investigator’s global assessment of response to therapy, WOMAC stiffness subscale, investigator’s global assessment of disease status, rescue paracetamol use, proportion of patients discontinuing due to lack of efficacy, and study joint tenderness. The team found that etoricoxib 60mg demonstrated efficacy significantly superior to placebo and was comparable to naproxen 500mg twice daily as assessed by the

primary efficacy endpoints. Secondary and other end points confirmed these results. Treatment effects were evident by day two, maximal by week two, and sustained over

15403 Etoricoxib Ad Pain Digital Book.indd 1

the entire 12 weeks. Etoricoxib was well tolerated for 12 weeks. They concluded that etoricoxib showed rapid and durable treatment effects in patients with OA of the

knee or hip and was generally well tolerated. In the Multinational Etoricoxib and Diclofenac Arthritis Longterm or MEDAL programme, etoricoxib 60mg-90mg was

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PAIN FOCUS generally GI or CV. According to the authors, the risk of discontinuing treatment because of GI adverse events was significantly lower with etoricoxib 90mg daily than diclofenac 150mg daily. Based on several large pooled analyses, etoricoxib was associated with a lower incidence of upper GI events (bleeding, perforation, obstruction, ulcer) than nonselective NSAIDs they concluded.

non-inferior to diclofenac 150mg daily in terms of the overall rate of arterial and venous thrombotic CV events. In the largest of these trials (n >23 000), the rates of treatment discontinuation for hypertension and oedema were higher with etoricoxib 90mg (and 60mg for hypertension) than with diclofenac. In a pooled analysis of 12 trials, thrombotic events appeared to be numerically (but not statistically) higher with etoricoxib than naproxen, but no difference between etoricoxib and non-naproxen NSAIDs was evident. In their study, Feng et al investigated whether etoricoxib increases the risk of GAEs compared with placebo, diclofenac, and naproxen in the treatment of patients with OA or RA. The authors analysed the results of randomised clinical trials (RCTs) that compared etoricoxib with placebo and other active drug for patients with OA or RA and reported data on GI safety. The follow-up time window for GAEs was defined as within 28 days after the last 28 MEDICAL CHRONICLE

dose of study medication. They found that in patients with OA or RA, etoricoxib did not increase the GAE risk compared with placebo but reduced the GAE risk effectively compared with diclofenac and naproxen during followup time. Huang and Tso evaluated the effectiveness and tolerability of etoricoxib in extremely elderly patients with chronic pain due to OA. Theirs was a prospective, singlecentre and single-arm study. Participants were selected based on their inadequate response to NSAIDs or other analgesics. They were switched to etoricoxib, 60mg once daily for four weeks, without prior medication washout. The primary endpoint was improvement in pain, assessed using the WOMAC after the four-week treatment. Other endpoints included the Brief Pain Inventory Short Form (BPI-SF), Treatment Satisfaction Questionnaire for Medication (TSQM), Short Form 36 (SF36), and European Quality of Life-5 Dimensions (EQ-5D). Safety and tolerability were

assessed by collecting adverse events data. They found that pain and disability scores measured by the WOMAC index were lower after treatment. BPI-SF showed a significant improvement in joint function when walking and performing normal work, while SF36 scores improved for seven out of 11 items after etoricoxib treatment. In addition, EQ5D showed a significant improvement in visual analogue scale scores. TSQM results demonstrated a higher patient perception of overall satisfaction. No adverse events were reported. The authors concluded that pain relief, joint function, quality of life, and treatment satisfaction improved significantly in elderly patients with OA after etoricoxib administration. Croom et al found that etoricoxib was generally well tolerated in clinical trials in patients with OA, RA and other musculoskeletal diseases such as AS and acute gouty arthritis. The most commonly reported drug-related adverse events were

COST EFFECTIVENESS Jansen et al evaluated the cost effectiveness of etoricoxib (90mg/day) relative to celecoxib (200mg/day or 400mg/day), naproxen (1 000mg/day) and diclofenac (150mg/day) in the initial treatment of patients with AS. A Bayesian cost-effectiveness model was developed to estimate the costs and benefits associated with initiating AS treatment with etoricoxib, celecoxib, diclofenac or naproxen. Efficacy, safety and medical resource and cost data were obtained from the literature. The obtained efficacy estimates were synthesised with a mixed treatment comparison meta-analysis. Treatment benefit and degree of disease activity, as reflected with Bath AS Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, were related to quality-adjusted life year (QALY) and ASspecific costs (related to BASDAI). Other cost outcomes related to drug acquisition, and GI and CV safety. There was a >98% probability that treatment with etoricoxib results in greater QALYs than the other interventions. Over a 30-year time horizon, starting AS treatment with etoricoxib was associated with about 0.4 more QALYs than the other interventions. At two years there was a 77% probability that etoricoxib had the lowest cost. This increased to >99% at 30 years. Etoricoxib is expected to save £13 620 (R228 692) relative to celecoxib (200mg/400mg), £9957 (R167 187) relative to diclofenac and £9863 (R165 608) relative to naproxen. For a willingness-to-pay ceiling ratio of £20 000 (R335 818) per QALY, there was a >97% probability that etoricoxib was the most cost-effective treatment. Additional analysis with different assumptions, including celecoxib 200mg, and ignoring cost-offsets associated with improvements in disease activity, supported these findings. This economic evaluation suggests that etoricoxib is the most cost-effective initial NSAID treatment for AS patients.

REFERENCES: Croom et al. Etoricoxib: A Review of its Use in the Symptomatic Treatment of Osteoarthritis, Rheumatoid Arthritis, Ankylosing Spondylitis and Acute Gouty Arthritis. Drugs, 2009. Cannon et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet, 2006. Feng X, Tian M, Zhang W et al. Gastrointestinal safety of etoricoxib in osteoarthritis and rheumatoid arthritis: A meta-analysis. PLoS One, 2018. Leung AT, Malmstrom K, Gallacher AE. Efficacy and Tolerability Profile of Etoricoxib in Patients with Osteoarthritis: A Randomized, Double-blind, Placebo and Active-comparator Controlled 12-Week Efficacy Trial. Current Medical Research and Opinion, 2002.

PAIN FOCUS

Myofascial pain syndrome on the increase MFTPs are categorised clinically dependent on their type. There are two types of MFTPs – active and latent (Travell and Simons, 1999).

YOFASCIAL PAIN SYNDROME (MPS) is a regional muscular pain with increasing prevalence and frequency associated with increasing age (Hou, 2002; Yap, 2007). MPS is characteristically caused by myofascial trigger points (MFTPs) (Wong and Wong, 2012). MFTPs are painful and sensitive areas within a taut band of muscle (Yap, 2007). MFTPs are categorised clinically dependent on their type. There are two types of MFTPs – active and latent (Travell and Simons, 1999). Alternative classifications include primary, secondary or satellite MFTPs dependant on the causative agent of the MFTPs (Travell and Simons, 1999). Essential clinical features of MFTPs include (Fernandez de Las Penas et al., 2005; Dommerholt et al., 2006; Cummings and Baldry, 2007): • A tender point within a taut band of skeletal muscle • A characteristic pattern of spontaneous referred pain • Recognition of pain on sustained compression over the tender point • A local twitch response (LTR) within the band of muscle on palpation. MFTPS are usually located within the taut band of contractured muscle fibres (Figure 2.2) and a local twitch response (LTR) has been described as a characteristic response of MFTPs (Lavelle et al., 2007). MFTPs contain a neurovascular bundle, the principal contents being motor nerve endings and nociceptive sensory afferent nerve endings (Baldry, 2001; Cummings and Baldry, 2007). Travell and Simons (1999) hypothesised that the pathophysiology of MPS and formation of MFTPs usually results from injured or ‘overstressed’ muscle fibres (Table 2). According to Travell and Simons (1999) understanding the location of motor end plates is vital for the diagnosis and management of MFTPs. Cummings and Baldry, (2007) state that the key pathophysiological abnormalities associated with MFTPs, principally appear to be located within the centre of the muscle in its motor end-plate zone. This zone is where the motor nerve, on entering a muscle divides into a number of branches, each of these branches has a terminal claw-like motor end-plate embedded into the surface of a muscle fibre (Figure 1) (Cummings and Baldry, 2007). Therefore, it seems that MFTPs appear to be intimately associated with the muscular motor end-plates (Cummings and Baldry, 2007). The precipitating factors (Table 2)

30 MEDICAL CHRONICLE

Myofascial pain syndrome (MPS) is a regional muscular pain with increasing prevalence and frequency associated with increasing age

lead to cell membrane damage, which is the initial event in muscle damage and development of the MFTP and is facilitated by the release of acetylcholine at the motor end-plates(Yap 2007; Ge et al., 2011). More acetylcholine may then be released, perpetuating the cycle of muscular pain and spasm, this increased release of acetylcholine at the motor endplates produces the spontaneous electrical activity (SEA) (Shah 2005; Ge et al., 2011), within a MFTP (Simons et al., 2002).The SEA is registered by intramuscular needle electromyography (EMG) when the muscle is at rest (Ge et al., 2011). Itis one of the characteristics of MFTPs (Simons et al., 2002). Hubbard and Berkoff’s (1993) study shows that, SEA was demonstrated at sites in a MFTP, whereas similar activity was not found at adjacent non-tender/non-MFTP sites (Lavelle et al., 2007) and according to Cummings and Baldry (2007) the work of Couppeet al., (2001) was the first blinded study to confirm the presence of SEA at MFTPs. Large extrafusal (alpha motor unit) skeletal muscle fibres are located outside the muscle spindle and the small intrafusal skeletal muscle fibres (gamma motor unit) (Figure 2.3) within the muscle spindle. According to Ge et al.,(2011) the spontaneous electrical activity originates from the extrafusal motor end-plate but not from the intrafusal motor endplate. Therefore, in this context, SEA is characterised by dysfunctional extrafusal motor end-plate potentials (Simons et al., 2002) within the muscle fibres which exhibit muscle tissue disruption in the form of a muscle cramp potential (Xu et al., 2010; Ge et al., 2011). It may also contribute to the formation of the taut muscular band in MFTPs, as the SEA is clinically represented by this focal muscle fibre contraction (Ge et al., 2011). Associated with these localised muscle cramps, are induced intramuscular

hypoxia, increased accumulation of algesic substances, direct mechanical stimulation of nociceptors and pain as a result of an inflammatory response (due to tissue degeneration) (Laferriere et al., 2008; Ge et al., 2011). Barbara et al., (2012), Cagnie et al., (2010) and Flogren et al., (2008) indicated changes in the microcirculation during these static low-level muscle contractions in MPS. These studies have demonstrated a decrease in oxygen saturation in the trapezius as well as a decrease in blood flow (Barbara et al., 2012). All of these contribute significantly to the formation of muscle tension and MFTPs (Laferriere et al., 2008; Ge et al., 2011). There are a great variety of physical therapies employed in the treatment of MPS which include: needling therapies such as dry needling and injection therapies or nonneedling therapies such as heat therapy, ultrasound, electrical therapy, medication (such as oral/topical NSAIDs), stretch and spray techniques and exercise therapies (Cummings and Baldry, 2007; Yap, 2007). The particular the needle effect has

been described as distinct from injected substances (Cummings and White, 2001) and a majority of manual and physical therapists adopt the needling technique (e.g. dry needling) which is the most common form of treatment for MFTPs (Tough and White, 2011). Of almost 9 000 physical therapists in South Africa, more than 75% are estimated to use the technique daily (Dommerholt et al., 2006). The needling procedure is described as an invasive procedure where the needle is inserted through the skin into a MFTP (Dommerholt et al., 2006; Hong, 2006). Its therapeutic effect relies in mechanical disruption or direct stimulation of the trigger points, thus producing the needle effect (Han and Harrison, 1997). It has been shown to decrease or even remove pain of myofascial origin and has been shown as an effective treatment in clinical practice (Dommerholt et al., 2006; Vernon and Schneider, 2009). Needling therapies are the most common form of treatment for MFTPs (Cummings and Baldry, 2007; Tough and White, 2011). According to a systematic review published

400 mg paracetamol

8 mg codeine phosphate

200 mg meprobamate

PAIN FOCUS causes a local twitch response, which relieves the SEA (Szymanski and Voss, 2007). According to Barbara et al., (2012), it has been suggested that dry needling may influence the microcirculation of the upper trapezius(in terms of increasing blood flow to the muscle and inducing a change of the chemical/inflammatory mediators), due to the increase in blood flow to the trigger point region (Shah and Gilliams, 2008; Kubo et al., 2010).

Dry needling is described as an invasive procedure in which an acupuncture needle is inserted into the skin

in 2001 of 23 randomised controlled trials (RCTs), when treating MFTPs with injection therapy, the injected substance and wet needling has no benefit over dry needling (Cummings and White, 2001; Cummings and Baldry, 2007). As such, it was suggested in the review that the effect derived from these therapies was most likely due to the mechanical effect of the needle (Cummings and White, 2001; Cummings and Baldry, 2007). Therefore, in effect, dry needling has been shown as an effective treatment for MFTPs (Dommerholt et al., 2006; Vernon and Schneider 2009). Dry needling is described as an invasive procedure in which an acupuncture needle is inserted into the skin and muscle (Dommerholt et al., 2006), with the needle being directed at the specific MFTP in order to elicit a local twitch response (Hong, 2006). With dry needling, an immediate relief of MFTP pain described as the â&#x20AC;&#x2DC;needle effectâ&#x20AC;&#x2122;, can be achieved if a local twitch response can be elicited during the procedure (Hong, 2006; Tough and White, 2011). Thus, the aim is to mechanically break up the MFTP and associated fibrotic scar tissue; therefore, the needle is targeted at the point of maximum tenderness within the taut band in order to achieve the therapeutic effect (Yap, 2007). Needling into the MFTP also induces a bio-electrical effect, which 32 MEDICAL CHRONICLE

Since the SEA is no longer present, the muscle contraction/cramps ceases, which lengthens the contractile element of the muscle and in so doing breaks the negative feedback loop responsible for sustaining the continuous muscle fibre contraction (Dommerholt, 2006; Szymanski and Voss, 2007).Research has shown that after dry needling and the eliciting of the twitch response, the chemical environment / microcirculation (Jimbo et al., 2008) as well as the SEA in the muscle returns to normal (Szymanski and Voss, 2007). In addition to the above, serotoninis secreted by nuclei that originate in the brain stem and project to many spinal cord areas, which include the dorsal horns of the spinal cord. Serotonin acts as an inhibitor of pain pathways in the spinal cord (Guyton and Hall, 2006). As such, according to Hong (2006) it is also possible that during dry needling of the MFTP, the strong pressure stimulation thus induced (due to insertion of the needle) of the MFTP nociceptors can provide very strong neural impulses to the dorsal horn cells in the spinal cord thus breaking the MFTP perpetuating cycle. This inhibiting effect on the nociceptors provides pain relief by spinal cord pathway modulation as well as by generalised neurohumoral stimulation and the release of endorphins (Yap, 2007). Therefore, the strongest analgesic effect is achieved when the most painful spot is precisely reached with a fine needle (Mense and Gerwin, 2010). In one of the first studies investigating dry needling on MFTPs, it was concluded that dry needling was effective at alleviating MPS (Lewit, 1979). The therapeutic effect of this technique has been studied indicating that dry needling can decrease or even eliminate MPS / MFTPs and is seen as an effective intervention (Mense and Gerwin, 2010; Dagenais and Haldeman, 2012). Based on this, dry needling of MFTPs has been shown as an effective treatment in clinical practice (Cummings and White, 2001; Dommerholt et al., 2006; Vernon and Schneider 2009).

Full references available on request

PAIN FOCUS

Shrugging off shoulder pain People with musculoskeletal pain sometimes complain that their entire bodies ache Shoulder pain may originate in the joint itself, or from any of the many surrounding muscles, ligaments, or tendons.

EOPLE WITH MUSCULOSKELETAL pain sometimes complain that their entire bodies ache WHAT CAUSES MUSCULOSKELETAL PAIN? The causes of musculoskeletal pain are varied. Muscle tissue can be damaged with the wear and tear of daily activities. Trauma to an area (jerking movements, auto accidents, falls, fractures, sprains, dislocations, and direct blows to the muscle) also can cause musculoskeletal pain. Other causes of pain include postural strain, repetitive movements, overuse, and prolonged immobilisation. Changes in posture or poor body mechanics may bring about spinal alignment problems and muscle shortening, therefore causing other muscles to be misused and become painful.

pinched nerve. Muscle relaxants are proved to provide relief from the agonising episodes of pinched nerve. TREATMENT Treatment should focus on the following: Ease muscle spasms: Apply dry or moist heat.

Reduce swelling: If the area is inflamed, apply ice for 20 minutes 4-8 times a day. Relieve pain: Give pain medication such as ibuprofen, acetaminophen, or naproxen. Ibuprofen is used to reduce fever and treat pain or inflammation caused by many conditions such as headache, toothache, back pain, arthritis, menstrual cramps, or

minor injury. Ibuprofen is used in adults and children who are at least six months old. Rest: The affected area should not be used for a day or two. Normal activities should be gradually resumed. Follow up: The person should see a doctor if pain doesn’t get better or worsens

SYMPTOMS People with musculoskeletal pain sometimes complain that their entire bodies ache. Their muscles may feel like they have been pulled or overworked. Sometimes, the muscles twitch or burn. Symptoms vary from person to person, but the common symptoms are: • Pain • Fatigue • Sleep disturbances SHOULDER PAIN Certain diseases and conditions affecting structures in the chest or abdomen, such as heart disease or gallbladder disease, may cause shoulder pain. Referred shoulder pain usually doesn’t worsen when the patient moves the shoulder. Shoulder pain causes include: • A vascular necrosis • Brachial plexus injury • Broken arm • Bursitis • Cervical radiculopathy • Dislocated shoulder • Frozen shoulder • Heart attack • Impingement • Sprains and strains • Osteoarthritis • Polymyalgia rheumatica • Rheumatoid arthritis • Rotator cuff injury • Separated shoulder • Septic arthritis • Tendinitis • Tendon rupture • Thoracic outlet syndrome • Torn cartilage MUSCLE SPASMS Muscle spasms are one of the major symptoms of a pinched nerve. On the contrary, muscle spasms may also cause a

DISINTEGRATE

PAIN Pain • Inflammation • Fever

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PAIN: A SENSORY AND EMOTIONAL EXPERIENCE Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). *Sponsored content

Spondyloarthropathies (SpA)are a group of chronic inflammatory rheumatic diseases that share overlapping features such as sacroiliitis, enthesitis and extraarticular manifestations. They can be divided into two main groups which describe the presenting symptoms (although these can overlap and one may progress to the other). • Axial SpA (spine and sacroiliac joints) • Peripheral SpA (peripheral joints). Recently, a group of key authorities in Pain Management held a symposium, sponsored by Kiara Health and Specpharm. The following article features some information from presentations that took place in the Western Cape.

THE CONCEPT OF PAIN Dr Magdalena Tarczynska, Anaesthetist and Head of Pain Management for non-cancer patients at Helen Joseph Hospital, spoke about the International Association for the

Study of Pain’s (IASP) comprehensive definition of pain. Pain is an unpleasant sensory and emotional experience associated with tissue damage (actual or potential). She spoke about pain being a complex entity, divided into acute (pain that lasts for less than three months) and chronic (ongoing pain, for longer than 3 months). Chronic pain is multidimensional, involving biological, psychological and social factors. “Psychologists might be the most important part of the journey,” she said. Dr Tarczynska explained that the majority of patients can’t be cured. “We need to teach them to manage their pain and to return to work.” In 2004, Prof Micheal Cousins et al analysed chronic pain in Anesthesia & Analgesia. Chronic pain was found to have its own symptoms and pathologies. “Since then, it is considered as a disease,” she said.

PAIN PHYSIOLOGY Dr Milton Raff, Anaesthesiologist

Q A

Dr Magdalena Tarczynska, Anaesthesiologist and Lecturer

Dr Robert Cooper, Rheumatologist

To treat pain effectively, medical professionals must determine the nature of the pain and manage the pain according to its physiology. Multimodal therapy is key to this.

and Head of a Pain Management Clinic at Netcare, Christian Barnard Hospital in Cape Town, presented on pain physiology and the evidence for Rhizotomy. He demonstrated that unrelieved acute pain results in abnormally enhanced physiological responses that lead to pronounced and progressively increasing pathophysiology. In turn, increasing pathophysiology leads to significant increase in organ dysfunction, which increases morbidity and mortality. Nociceptive pain results from activity in neural pathways secondary to actual tissue damage or potentially tissue-damaging stimuli. It is chronic pain that is initiated by nervous system lesions or dysfunction and can be maintained by a number of different mechanisms. It is responsive to nonsteroidal anti-inflammatory drugs (NSAIDs), coxibs, paracetamol and opiates. Traumatic/ inflammatory pain is responsive to NSAIDs, coxibs, paracetamol and opiates. Maladaptive or nonphysiological (neuropathic, dysfunctional) pain is not protective. It is not usually responsive to NSAIDs, coxibs and paracetamol.

CHRONIC PAIN: AXIAL SPONDYLOARTHRITIS

Do NSAIDs and coxibs opioid spare? The answer is undoubtedly yes. They must be given intra- or immediately postoperative to have effect. This results in a decrease in pain scores, the time to first opioid request is increased, and less opioid is consumed in the first 48 hours.

Dr Milton Raff, Anaesthesiologist

Dr Robert Cooper, Rheumatologist at the Winelands Rheumatology Centre in Stellenbosch, presented on rheumatoid arthritis and drug interactions, as well as the recommended management of Spondyloarthritis (SpA). Chronic, "inflammatory" lower back or alternating buttock pain is present in the vast majority of patients with Axial SpA, which is typified by an insiduous onset in younger patients (<45 years of age), improvement of the pain and stiffness with exercise, early morning stiffness and night pain. Other musculoskeletal manifestations of SpA include arthritis, enthesitis and dactylitis. Extra-articular manifestations such as anterior uveitis, psoriasis and inflammatory bowel disease (IBD) are also characteristic for SpA. Historically, patients with advanced axSpA were recognised by their characteristic posture and by the presence of typical radiographic findings on plain radiograph, of which sacroiliitis is the hallmark feature. Only recently, it has been properly acknowledged that radiographic sacroiliitis is a rather late finding in the disease course of many patients with axial SpA. MRI may show signs of inflammation much earlier than changes are seen on plain radiographs, and that patients can also be diagnosed based on a typical clinical pattern, even in the continued on next page >>

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presence of normal imaging tests. The term axial SpA comprises the whole spectrum of patients with radiographic sacroiliitis (radiographic axSpA) and those without (non-radiographic/preradiographic axSpA), which may or may not progress to definite radiographic sacroiliitis over time.

TREAT-TO-TARGET One of the important concepts, which was first implemented in the treatment of conditions in other disciplines, and is

currently an important part of routine practice for most rheumatologists, is treating to target. “If you don’t set a realistic, mutually agreed upon target when first treating a patient, you’re unlikely to reach a specific desired outcome. The target must be individualised and, once reached, it must be sustained . In order to achieve this, you have to constantly reassess the disease and adapt the therapy to make sure that you are reaching the desired outcomes. The only way to do this is, is with regular monitoring of the patient, and as time

passes, the target might change, as comorbidities emerge. “In order to manage disease optimally, we often have to use a combination of disease-modifying drugs. The more drugs you add, the more you have to know about the drugs you are prescribing, their safety and possible interactions,” Dr Cooper said.

ASAS-EULAR PRINCIPLES It was agreed that axSpA is a potentially severe disease with diverse manifestations, usually requiring

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multidisciplinary management coordinated by the rheumatologist. The primary goal of treating the patient with axSpA is to maximise health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalisation of function and social participation. The optimal management of patients with axSpA requires a combination of non-pharmacological and pharmacological treatment modalities. Treatment of axSpA should aim at the best care and must be based on a shared decision between the patient and the rheumatologist. According to the updated A SAS-EULAR recommendations, the treatment of patients with axSpA should be individualised according to the current signs and symptoms of the disease (axial, peripheral, extra-articular manifestations) and the patient characteristics including comorbidities and psychosocial factors. Disease monitoring of patients with axSpA should include patientreported outcomes, clinical findings, laboratory tests and imaging, all with the appropriate instruments and relevant to the clinical presentation. The frequency of monitoring should be decided on an individual basis depending on symptoms, severity and treatment. Patients should be educated about axSpA and encouraged to exercise on a regular basis, to stop smoking and physical therapy should be considered. For axial and peripheral disease, patients suffering from pain and stiffness should use an NSAID as first-line drug treatment up to the maximum dose, taking risks and benefits into account. “We have patients who are able to control symptoms just by the use of regular NSAIDs,” Dr Cooper said. For patients who respond well to NSAIDs, continuous use is preferred if otherwise asymptomatic. Analgesics, such as paracetamol and opioid drugs, might be considered for residual pain after previously recommended treatments have failed, are contraindicated, and/or poorly tolerated. Glucocorticoid injections directed to the local site of musculoskeletal inflammation may be considered. Patients with axial disease should not receive long-term treatment with systemic glucocorticoids. Patients with purely axial disease should normally not be treated with csDMARDs; sulfasalazine may be considered in patients with peripheral arthritis. bDMARDs should be considered in patients with persistently high disease activity despite conventional

PAIN FOCUS CLINICAL PAIN CPD

Peripheral disease

Axial disease

NSAIDs

TNF blockers

Surgery

Local corticosteroids

Time

Education excercise, physical therapy, rehabilitation, patient associations, self help groups

Analgesics

Sulfasalazine

Figure 1. Recommended management of axSpA, based on clinical expertise and research evidence. The disease progression with time moves vertically from top to bottom.

treatments. Current practice is to start with TNFi therapy. The primary goal of treating the patient with AS is to maximise long-term health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalisation of function and social participation. It was recommended that NSAIDs are administered in a full anti-inflammatory dosage. This can be based on the ASAS20 response of >70%, an ASAS40 response in >50% of the patients starting with an NSAID in early disease or 35% of patients in ASAS partial remission. However, important consideration needs to be given to the potential side effects of NSAIDs, especially when administered chronically. According to the ASAS/EULAR 2016 update: “NSAIDs should therefore only be prescribed if patients are symptomatic. If so, treatment should be advised to the maximum tolerated dose, continuously weighing the risks against the benefits. Moreover, while there is much discussion on the longterm safety of NSAIDs especially in relatively young patients, data from two studies have suggested that lack of exposure to NSAIDs is associated with an increase in mortality.”

According to the recommendation, given the risks of long-term NSAID use, the question about which patients require continuous NSAID treatment is valid. Trial data have suggested that the continuous use of NSAIDs in patients with an elevated CRP results in reduced progression of structural damage in the spine in comparison to on-demand use only. Similar results were found in a cohort study comparing high-dose and low-dose NSAID use. However, a recent randomised trial did not confirm this effect, casting doubts on the potential structural effects of NSAIDs. It was suggested during the task force discussions that the protective effects of NSAIDs may be specific for certain NSAIDs. In the absence of evidence, it was finally decided to base a decision of continuous use of NSAIDs to the symptoms of the patient rather than on a possible protective effect regarding structural progression. If symptoms recur after stopping or dose reduction of an NSAID, continuous use should be advised. This was accepted by a two-third majority in the second round of voting. Whether continuous NSAID use may be beneficial in patients with risk factors for syndesmophyte

progression (presence of syndesmophytes, elevated CRP, longstanding disease, spinal inflammation on MRI) remains a topic on the research agenda.

ANTICOAGULATION AND ARTHRITIC PAIN According to Dr Chris Nel, Rheumatologist at Netcare Universitas Hospital Bloemfontein, there is inadequate awareness of treatment options for axSpA. He emphasised the importance of regular anti-inflammatories even in advance disease. There is a high risk for spinal fractures due to rigidity and osteoporosis, and even minor trauma could be catastrophic. The fracture prevalence is 4%-18%, with cervical spine being the most common injury site (C5-C6 and C6-C7).

CONCLUSION Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective against the major symptoms of axSpA (pain and stiffness) and may have disease-modifying properties including retarding progression of structural damage in the spine. Therefore, NSAIDs, unless contraindicated, are the treatment of choice for the majority of patients

NSAIDs should therefore only be prescribed if patients are symptomatic. If so, treatment should be advised to the maximum tolerated dose, continuously weighing the risks against the benefits

with axSpA. Beyond NSAIDs, only tumour necrosis factor (TNF) α blockers are effective and approved for the treatment of active AS. Pharmacological therapy of AS should always be combined with nonpharmacological treatment including education and regular exercise/physiotherapy.

References available on request

Answer online at www.medicalacademic.co.za. Go to page 62 for step-by-step instructions

MEDICAL CHRONICLE 37

PAIN FOCUS

Simple analgesics could prove effective in the

management of tension headaches

The pharmacist plays a very important role in the diagnosis and referral of patients presenting with headaches, dispensing of medications, and counselling of patients.

HE PHARMACIST PLAYS a very important role in the diagnosis and referral of patients presenting with headaches, dispensing of medications, and counselling of patients. TENSION HEADACHE Headache is pain originating in the forehead, scalp, face (including the orbito-temporal area), anterior of the head, and rear of the head. There are many different causes for developing a headache. The intensity, site, and duration of pain may provide an indication of the underlying cause. Tension headache is by far the most common primary headache, while migraine headaches are the second most common. Headaches are a common symptom of many different conditions and have many causes. It is important to enquire about the presenting characteristics of a headache to determine if it is a tension, migraine, or cluster headache. Management should be aimed at both stopping and treating the pain or by prevention of the headaches. TENSION HEADACHE Causes of this kind of headache are associated with muscle spasms in the neck and occipital muscles e.g. stress, tension, fatigue, excessive activity, rage, depression, immobile or incorrect neck positions such as sitting in the same position for a long time, and minor trauma to the head. This kind of headache is common and 75% of patients are female. CLINICAL FEATURES The headache may persist for a few hours or days and are associated with stressful situations but are not associated with physical activity. Exercise may relieve the pain. The pain gets worse as time progresses. Pain is generalised and of

38 MEDICAL CHRONICLE

a pressing or tightening nature, mild to moderate in nature, bilateral in location, and spread all over the head. The headache is often described as non-throbbing, cap-like, crushing, or like a “tight band” around the head. It affects the bifrontal or bioccipital regions and tends to get worse through the day. Nausea is absent, but photophobia or phonophobia may be present. Since this kind of headache is associated with spasms of the occipital and neck muscles, palmation of the neck will reveal tenderness. If attacks are occasional the condition is referred to as an episodic tension headache, whereas if it occurs more than 15 days/ month for more than six months/year, it is referred to as a chronic tension headache.

PHARMACOLOGICAL MANAGEMENT Simple analgesics prove to be effective in the management of this kind of headache. Schedule 2 analgesic combinations which have a skeletal muscle relaxant or antihistamine are often given. Preparations containing paracetamol plus chlormezanone are popular, as are combinations of paracetamol, codeine phosphate, caffeine, and doxylamine succinate. Mebrobamate is also very useful for the treatment of these kinds of headaches due to its muscle relaxation properties. Preventative treatment may include anti-anxiety medications, should there be an anxiety component or antidepressant medications, such as

tricyclic antidepressants, and should there be an underlying depression component. Monoamine oxidase inhibitors have also been shown to be effective since these kinds of headaches, like migraine headaches, are due to low serotonin levels. NON-PHARMACOLOGICAL MANAGEMENT • Assist the patient in identifying the cause of the headache. • Provide reassurance and an explanation of the kind of headache and its management. • Teach relaxation techniques or refer the patient for physiotherapy. AUTHOR: Dr Liesl Brown, BPharm, MSc (Pharm) Cum Laude, PhD

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FAST AND EFFECTIVE PAIN RELIEF IS NEEDED1 89% of 196 Myprodol® users in a recent survey agreed that Myprodol® is most effective at relieving pain*2 Myprodol® is indicated for the relief of mild to moderate pain of inflammatory origin with or without fever3,4

Original. Dependable. Since 1987.3 § IMS June 2020, N2B non-narcotic analgesics. ‡IMS June 2020, N2B1 non-narcotic analgesics. *Pain Medication Consumer Market Assessment of 227 consumers; March 2018.2 REFERENCES: 1. Jung Y-S, Kim DK, Kim M-K, et al. Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: a singlecenter, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model. Clinical Therapeutics 2004;26(7):1037-1045. 2. Pain Medication Consumer Market Assessment, March 2018. 3. Myprodol® Capsules approved package insert, May 1987. 4. Myprodol® Suspension approved package insert, June 1994.

MYPRODOL® Capsules. Each capsule contains codeine phosphate 10 mg; ibuprofen 200 mg; paracetamol 250 mg. Reg. No. T/2.8/244. MYPRODOL® Suspension. Each 10 ml contains codeine phosphate 10 mg; ibuprofen 200 mg; paracetamol 250 mg. Reg. No. Y/2.8/119. For full prescribing information refer to the package insert approved by the medicines regulatory authority. 202008121050982. Adcock Ingram limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021,South Africa. Tel. +27 11 635 0000. www.adcock.com

CLINICAL | CANNABIS

PAIN FOCUS

Medical Cannabis – What’s the evidence?

Clinical evidence of the indications for the use of medical cannabis is currently supported by a limited evidence base, but the field is evolving.

EDICAL CANNABIS HAS been shown to be effective for certain conditions, but the benefit for most investigated indications is limited. THC and CBD are the most widely researched phytocannabinoids. CANNABINOIDS AND MEDICAL CANNABIS The pharmacologically active ligands in medical cannabis are the cannabinoids. Over the past years, almost 200 cannabinoids have been identified, and the type of cannabinoids differs depending on whether they are endogenous (endocannabinoids), plant derived (phytocannabinoids) or synthetic. The endocannabinoid system consists of endogenous lipid-based neurotransmitters that bind to cannabinoid receptors expressed widely throughout the body. The endocannabinoid system purportedly has two types of receptors, CB1 and CB2. CB1 receptors are abundant in the brain and central nervous system but are also found in various other tissues. CB1 receptors are thought to regulate functions such as memory, nausea and vomiting, nociception, sleep and appetite. CB2 receptors are mostly found in immune cells and the cardiovascular, gastrointestinal and reproductive systems, where it is considered to regulate various functions. The CB1 and CB2 receptors can be stimulated by endocannabinoids, phytocannabinoids or synthetic cannabinoids. An important consideration is that the affinity and potency of the different cannabinoids for CB1 and CB2 receptors differ such that efficacy and safety of one cannabinoid cannot be applied to another. Phytocannabinoids are isolated from the Cannabis sativa and Cannabis indica plants. THC and CBD are the most widely researched phytocannabinoids. The psychoactive effects of cannabis have been attributed to THC, a major compound of the C. sativa plant, while CBD is thought to inhibit these effects. THC functions as an agonist with high affinity for both CB1 and CB2 receptors. CBD has low affinity for CB1 and CB2 and displays antagonism and inverse agonism at these receptors. This implies that the ratio of THC and CBD in phytocannabinoids would affect the ultimate clinical effect. The strain of cannabis and the cultivation environment, such as soil type, irrigation, harvesting and processing, all affect the quality and composition of phytocannabinoids. Different parts of the cannabis plant also have differing concentrations of phytocannabinoids, with THC generally

40 MEDICAL CHRONICLE

being most abundant in the flowers and leaves, and CBD in the leaves and stems. CANNABINOID-APPROVED DRUGS To date, the US Food and Drug Administration (FDA) has approved three drugs that contain cannabinoids: A plantderived CBD solution, and two synthetic cannabinoids structurally related to THC, nabilone and dronabinol. A purified form of THC and CBD in a 1:1 ratio, known as nabiximols, has been approved by Health Canada and several other countries. Approved medical cannabis products on the market are oral formulations administered either as capsules, oral solutions or oromucosal sprays. These standardised preparations aim to provide accurate dosing and improve safety. Evidence supporting benefit from the use of medical cannabis exists for two drugresistant childhood forms of epilepsy, Dravet syndrome and Lennox-Gastaut syndrome. Three randomised controlled trials (RCTs) assessed the effect of a pharmaceutical plant-derived CBD solution, and found that when added as adjuvant therapy at the maximum recommended dose, it led to a significant reduction in the median frequency of monthly seizures when compared with placebo for Lennox-Gastaut syndrome (–18%; 95% confidence interval (CI) –31.8 - –4.4; p=0.009), and for Dravet syndrome (–22%; 95% CI –41.1 –5.4; p=0.01). Based on these findings, the FDA approved the plant-derived CBD for Dravet and LennoxGastaut syndromes, and approval by the EMA followed thereafter. Long-term therapy with CBD in these epilepsy syndromes has also found sustained response and acceptable tolerability. For other conditions, there is moderate evidence for the management of chemotherapy-induced nausea and vomiting (CINV) and multiple sclerosis (MS)-associated spasticity. The synthetic cannabinoids dronabinol and nabilone

showed the best efficacy in reducing CINV, but the risk of bias and lack of consistency of findings in trials limit their recommendation. Nevertheless, dronabinol and nabilone have both received FDA approval for refractory CINV. In April 2019, SAHPRA announced that the first three licences permitting the sale of medicinal cannabis would be issued. We are likely to see many more of these, as a result of their backlog project.

REFERENCES 1. Minister of Justice and Constitutional Development and others v Prince and others [2018] JOL 40399 (CC); 2. Prince v Minister of Justice and Constitutional Development and others and related matters [2017] 2 All SA 864 (WCC)); 3. Mthembu and others / NCT Durban Wood Chips [2019] 4 BALR 369 (CCMA); 4. Item 7, Schedule 8, Labour Relations Act 66 of 1995. 2. Van Rensburg, R et al. Medical cannabis: What practitioners need to know. South African Medical Journal, [S.l.], v. 110, n. 3, p. 192-196, feb. 2020. ISSN 2078-5135. Available at: http://www.samj.org.za/ index.php/samj/article/view/12860.

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MEDICAL CHRONICLE | APRIL 2020

CPD| PAIN

PAIN FOCUS

Managing chronic pain during the

Covid-19 pandemic The world has been fundamentally changed by the Covid-19 pandemic. Yet, the more things change the more they stay the same.

HRONIC PAIN IS one of the most prevalent diseases in the world and is also one of the most poorly recognised and treated conditions globally. The Covid-19 pandemic has exacerbated the paucity of medical care available for patients afflicted with chronic pain in South Africa and internationally. In March 2020 the South African government instituted a lockdown of the country in an effort to slow down the spread of the Covid-19 infection. This resulted in a sudden stop of all nonemergency medical care including chronic pain management services in both the private and public sectors. With the gradual easing of lockdown restrictions these services are slowly resuming, however, many patients continue to have limited access to pain management services.

THE RISKS AND IMPACT OF UNTREATED PAIN Pain is a frequent reason for patients going to a hospital casualty or emergency department for management. Pain accounts for 45-75% of emergency department patient presentations in the USA, with at least half of these patients having moderate or severe pain.1, 2, 3 The increase in patient visits to manage Covid-19 has proven challenging for many hospital systems around the globe, and it would not be surprising that non-urgent non-Covid-19 cases are probably slipping through the cracks of an already overloaded system in South Africa. The increased demand for healthcare, together with reduced human resources (due to staff Covid-19-related illness and the need to reduce staff numbers on shifts

for social distancing) has led to further limitations in the availability of health resources for chronic pain patients. The impact of the reduction of pain treatment has led to the unintended consequences of increased pain, reduced function, increased reliance on opioid medications and potentially increased morbidity, due to the impact of untreated disease on patients afflicted with chronic pain. The stress, anxiety, and difficulties associated with the isolation imposed by the pandemic may worsen painful symptoms, increase anxiety, and lead to functional decline.4 These problems are not trivial; untreated chronic pain can exacerbate depression in 50% of patients and lead to suicidal ideation is 35%.5 Pain prevention and control – particularly for chronic pain –will inevitably be disrupted

Prof Sean Chetty, Associate Professor and executive head of Department of Anaesthesiology and Critical Care, Stellenbosch University

by the Covid-19 pandemic. In the short term, planned diversion of resources is already taking place (eg cancelling elective surgical procedures for chronic disease management in both the public and private healthcare sectors of the country) and unplanned scenarios (eg medication shortages due to panic buying and inaccessibility of remaining healthcare options during movement restrictions) are placing additional strain on the system. Longer-term, healthcare workers are likely to be at higher risk of lasting psychological morbidity based on experiences from the 2002 Asian SARS epidemic.6 This will not only reduce the available healthcare human resources in South Africa but will also put these providers at risk for developing chronic pain. Prevention of chronic pain within populations currently depends on best

1,2

References: 1. Matsumoto AK, Cavanaugh PF (Jr). Etoricoxib. Drugs of Today (Barc) 2004;40(5):395-414. 2. Coricib® 30 mg, 60 mg, 90 mg and 120 mg tablets package insert, February 2020. S3 Coricib 60 mg / 90 mg / 120 mg. Each film coated tablet contains etoricoxib 60 mg / 90 mg / 120 mg. Reg. Nos: 51/3.1/1149.1145; 51/3.1/1150.1146; 51/3.1/1151.1147. Applicant: Ranbaxy Pharmaceuticals (Pty) Ltd., a Sun Pharma company. Reg. No.: 1993/003111/07. 14 Lautre Road, Stormill Ext.1, Roodepoort, 1724. Tel: +27 11 495 0100. Fax: +27 11 495 0150. www.sunpharma.com For full prescribing information, refer to the Professional Information approved by the Regulatory Authority.

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MEDICAL CHRONICLE | JULY 2020 23 MEDICAL CHRONICLE 41

CPD |FOCUS PAIN PAIN practice management of acute pain and early recognition of the risk of progression to chronic pain.7 In the current state of lockdown in South Africa, and the diversion of resources towards Covid-19 related healthcare, we are unable to effectively manage acute pain and will undoubtedly also be less likely to detect the early signs of chronic pain. NOT TREATING CHRONIC PAIN When people with chronic pain are denied assessment and treatment, their condition can worsen significantly – spontaneous recovery is extremely rare. People living with chronic pain have the largest global morbidity, measured by years lived in

disability.8 Not treating chronic pain will have consequences for individuals, healthcare systems and providers in the short- and long-term, increasing quantity, severity, and complexity of healthcare needs. CONFOUNDING FACTORS There are a number of therapeutic interventions used in the management of chronic pain that confound the influence that the Covid-19 pandemic has on patients with chronic pain. OPIOIDS Opioids are a class of drugs that can affect the immune system but different opioids may have varying effects.9-11 Patients on

chronic opioid therapy are more susceptible, in general, to secondary infections, and it is presumed they may therefore be more susceptible to Covid-19 infection as well. Furthermore, the respiratory symptoms of Covid-19 may be exacerbated in patients who take opioids, as these patients are at elevated risk for respiratory depression. There are currently no recommendations to discontinue opioids in patients on chronic opioid therapy, but healthcare workers should be aware of their immunosuppressive properties. STEROIDS Steroids suppress the immune system even more than opioids, making their

Neck muscle spasm? Back muscle spasm? Acute muscle spasm?

Rapid and effective pain relief1,2 Rapid onset of action1,2 Effective relief from pain1 Sustained analgesic and anti-inflammatory efficacy1

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Sustained efficacy for painful muscle spasm2,4,6 COX – cyclooxygenase; NSAIDs – nonsteroidal anti-inflammatory drugs; GI – Gastro intestinal References: ® References: 1. Matsumoto AK, Cavanaugh PF (Jr). Etoricoxib. Drugs of Today (Barc)with 2004;40(5):395-414. Coricib 30 mg, 60 double-blind, mg, 90 mg and 120 mg tablets studies of identical design. Curr Med Res 1. Malanga GA, Ruoff GE, Weil AJ, et al. Cyclobenzaprine ER for muscle spasm associated low back and neck 2. pain: two randomized, placebo-controlled & Opin 2009;25(5):1179-1196. 2. Weil AJ, Ruoff GE, NalamachuA, S, et al. Efficacy and tolerability of cyclobenzaprine release for acute muscle spasm: pooled analysis. Postgrad Med 2010;122(4):158-169. 3. package insert, February 2020. 3. Escudero-Contreras Vazquez-Mellado J, Collantes-Estevez C, et al.extended Update on the clinical pharmacology ofAetoricoxib, a Borenstein DG, Korn S. Efficacy of a low-dose regimen of cyclobenzaprine hydrochloride in acute skeletal muscle spasm: Results of two placebo-controlled trials. Clin Therapeutics 2003;25(4):1056-1073. 4. Ruoff GE. potent cyclooxygenase-2 inhibitor. Future Rheumatol 2007;2(6):545-565. 4. Brooks P, Kubler P. Etoricoxib for arthritis and pain management. Ther & Clin Risk Man Once-daily cyclobenzaprine extended-release: A simple alternative to control muscle spasm. Clinical update. Family Practice News. Available from http://www.familypracticenews.com//fileadmin/content_pdf/fpn/ 2006;2(1):45-57. 5. Data on file. Bioequivalence study of etoricoxib. supplement_pdf/wxhpzdcj_FPNEWS_Supplement32.pdf Accessed 14 Mar 2016. 5. Darwish M, Chang S, Hellriegel ET. A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: A randomized, double-blind, two-period crossover study in healthy volunteers. Clin Therapeutics 2009;31(1):108-114. 6. MYPROCAM 15 and MYPROCAM 30 extended release capsules approved S3 Coricib mg /2014. 90 mg / 120 mg. Each film coated tablet contains etoricoxib 60 mg / 90 mg / 120 mg. Reg. Nos: 51/3.1/1149.1145; 51/3.1/1150.1146; package insert,60 March

Applicant: Ranbaxy Pharmaceuticals (Pty) Ltd., a Sun Pharma company.15Reg. No.: 1993/003111/07. S5 51/3.1/1151.1147. MYPROCAM 15 capsules. Each extended-release capsule contains cyclobenzaprine hydrochloride mg. Reg.No. 44/17.3/0904 S5 Roodepoort, MYPROCAM 1724. 30 capsules. Each capsule contains hydrochloride 30 mg. Reg.No. 44/17.3/0905 Tel: +27 11extended-release 495 0100. Fax: +27 11 495 0150.cyclobenzaprine www.sunpharma.com For full prescribing information refer to the package insert approved by the medicines regulatory authority. 10270847 06/2016. Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021 South Africa. Tel. +27 11 635 0000. www.adcock.com.

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use potentially dangerous in high-risk patients.12 International guidelines state that physicians may continue to perform epidural and steroid injections in appropriate patients during the Covid-19 pandemic but should use the lowest possible effective dose, and patients should be informed about their risk for infection and suppressed immune responses.12 Steroids are associated with secondary adrenal insufficiency and altered immune system response.13 Steroids are to be used with caution in Covid-19 patients.14 NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDs) While there is controversy about using NSAIDs for the treatment of Covid-19 symptoms of fever, headache and myalgia, neither the Food and Drug Administration (FDA) of the United States nor the European Medicines Agency (EMA) have found an association between NSAIDs and worsened Covid-19 symptoms.15,16 This issue is not yet clarified, and it is therefore inappropriate to avoid or discontinue NSAIDs in Covid-19 patients.17 It has been recommended that chronic pain patients on NSAID therapy should continue their NSAIDs and not rotate to opioids.18

Pain is a frequent reason for patients going to a hospital casualty or emergency department for management. Pain accounts for 4575% of emergency department patient presentations in the USA DEVICE THERAPY i. Intrathecal drug pumps Implanted intrathecal pumps that deliver medications such as opioids, baclofen, and bupivacaine directly to the intrathecal space, pose an important problem during the pandemic. Such pumps must be refilled by a qualified healthcare professional, as the reservoir runs low. The abrupt discontinuation of certain medicines can be associated with severe, even life-threatening, symptoms. In addition, emptying the reservoir on the pump may cause irreparable damage to the device.

ii. Neuromodulatory devices Neuromodulation may be continued but new implants are considered elective and should be deferred until after the pandemic.19 Patients with difficulties or technical problems with neuromodulation may be able to consult remotely with a clinician or technician for guidance, and the need for an in-person visit should be determined on an individual basis.19 An in-person visit might be required for suspected device infection or

PAIN FOCUS

CPD| PAIN

A large trial delivering psychological therapy through an online pain course has shown improvement in pain, disability, and emotional functioning compared with waiting list but few differences between groups with varying amounts of therapist contact

loss of function leading to intolerable pain. A deeply infected device or lead must be explanted as soon as possible.20 This should be regarded as a non-elective procedure. WHAT SHOULD WE BE DOING? Be more aware of chronic pain features in patients who you do see for other reasons. Understandably, patients are more cautious about visiting their healthcare providers for ‘minor ailments’ and therefore will not seek care until later in the trajectory of their disease. It is important, now more than ever, to be hyper-vigilant and to ask enquiring questions when you see patients for other reasons, if you suspect a chronic pain condition. Early identification of chronic pain may make a huge difference in the patient’s long-term prognosis.

Manage acute pain more aggressively Poorly managed acute pain is a major risk factor for central sensitisation and development of chronic pain conditions. Patients who have acute injuries should have their acute pain appropriately managed so that they are able to rehabilitate and recuperate adequately.

Consider telemedicine Not long after the lockdown was announced in South Africa, the Health Professions Council of South Africa (HPCSA) gazetted rules that allow for the implementation of telemedicine in South Africa. These regulations are limiting, however, they do provide an avenue that

must be explored as an option in your practice to manage chronic pain patients. It is important to be aware that this form of healthcare intervention may not be appropriate for all patients. Triage of pain patients may be helpful in terms of differentiating those who may be adequately treated by telemedicine versus in-clinic consultations. Triage factors include acuity and severity of pain, whether or not the patient has comorbid psychiatric conditions, occupational considerations, and social situation (such as whether the patient is also a caregiver or has children, and therefore cannot travel to a healthcare provider for treatment during the lockdown).12 Most innovation in telemedicine has been in the development of internet delivered therapies for people with chronic pain. Many remotely delivered programmes can be accessed directly and have minimal requirements. Interdisciplinary evaluations can be modified for distance use before the patient appointment, supporting history and examination. Even aspects of the physical examination can be undertaken virtually, for example, in judging appearance, movement, or in self-examination under guidance. Although there are limitations to the lack of hands-on physical examination possible with telemedicine, a modified virtual examination may allow an initial treatment plan to be started. The first Cochrane systematic review of technological interventions for chronic pain in adults found 15 studies with 2000 participants.21 Several systematic reviews have been published after this one.22-25 These reviews have identified small to

moderate reductions in pain, disability and distress in intervention groups compared with control groups.22,24 Remotely delivered physical exercise interventions are also available, with benefits comparable with usual care for reducing pain and beneficial compared with no treatment.26 ‘Therapeutic alliance’ is important but may be more challenging to establish, foster and maintain remotely. That said, a large trial delivering psychological therapy through an online pain course has shown improvement in pain, disability, and emotional functioning compared with waiting list but few differences between groups with varying amounts of therapist contact.27 In South Africa, a pilot project using this model is now being delivered at two academic hospitals in the Western Cape. Understanding who struggles to engage and use eHealth provision is crucial to maximise effectiveness, as are concerns about privacy, transparency, and training needs of staff accustomed to face-toface working. Telemedicine is safe but requires the patient to have access to the internet and the ability to use a smartphone or computer. For many patients in South Africa, this may not be a viable option.

Where required, see patients with adequate PPE and protection. Even in times of pandemic, some pain patients will need in-person care.19 In such cases, patients and healthcare providers should be screened for Covid-19 symptoms, and appropriate protective measures taken in your practice to protect the patient and the healthcare workers.19

Try to avoid interventions while SA is still experiencing escalating Covid-19 patients numbers. Interventional pain management procedures can be extremely efficient in managing chronic pain, however, all these procedures will usually require admission to a hospital or day clinic. This may expose these patients, unnecessarily, to the risk of Covid-19 infection and also competes for hospital resources that may be better used (at present) to manage Covid-19 patients. Where possible, try to manage these patients conservatively, until such time that less strain is being placed on the health care resources of the country. CONCLUSION Preventing chronic pain is complex at the best of times, but in a global health pandemic, risk factors for pain morbidity and mortality will be magnified. It is imperative that medical practitioners treat chronic pain to minimise the immunosuppressive and deconditioning consequences of untreated suffering, and potentially increase survival in patients, such as those with cancer.29, 30 When our patients, communities and healthcare systems are being adversely affected by a viral pandemic, optimising the overall well-being of our chronic pain patient populations should also be a top priority.

References available on request.

This is a CPD-accredited article. To earn 3 points, go to www.medicalacademic.co.za and look for the post called MEDICAL CHRONICLE 43 Medical Chronicle July CPD and answer the questionnaire.

PAIN FOCUS

Do NSAIDs make

COVID-19 worse? In a statement released by the European Medicines Agency (EMA), it confirms it is aware of reports, especially on social media, which raise questions about whether non-steroidal anti-inflammatory medicines (NSAIDs) such as ibuprofen could worsen coronavirus disease (COVID-19).

RITISH PHARMACOLOGICAL SOCIETY, and their President, Prof Sir Munir Pirmohamed, said: “The British Pharmacological Society has responded to concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, could make the symptoms of the novel coronavirus infection, COVID-19, worse. “As COVID-19 is a new disease, evidence about it is still emerging. On 17 March 2020, the NHS updated its advice to include: There is currently no strong evidence that ibuprofen can make COVID-19 worse. However, until we have more information, people should take paracetamol to treat the symptoms of coronavirus, unless they have been told by their doctor that paracetamol is not suitable for them.” “EMA is monitoring the situation closely and will review any new information that becomes available on this issue in the context of the pandemic,” the agency said. In May 2019, EMA’s safety committee (PRAC) started a review of the nonsteroidal anti-inflammatory medicines ibuprofen and ketoprofen following a survey by the French National Agency for Medicines and Health Products Safety (ANSM) which suggested that infection due to chickenpox (varicella) and some bacterial

Mypaid Print ready.pdf

2020/07/05

infections could be made worse by these medicines. The product information of many NSAIDs already contains warnings that their anti-inflammatory effects may hide the symptoms of a worsening infection. The PRAC is reviewing all available data to see if any additional measure is required.

The British Pharmacological Society has responded to concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, could make the symptoms of the novel coronavirus infection, COVID-19, worse When starting treatment for fever or pain in COVID-19, patients and healthcare professionals should consider all available treatment options including paracetamol

and NSAIDs. Each medicine has its own benefits and risks which are reflected in its product information and which should be considered along with EU national treatment guidelines, most of which recommend paracetamol as a first treatment option for fever or pain. In line with EU national treatment guidelines, patients and healthcare professionals can continue using NSAIDs (like ibuprofen) as per the approved product information. Current advice includes that these medicines are used at the lowest effective dose for the shortest possible period. Patients who have any questions should speak to their doctor or pharmacist. There is currently no reason for patients taking ibuprofen to interrupt their treatment, based on the above. This is particularly

important for patients taking ibuprofen or other NSAID medicines for chronic diseases. Further to the ongoing PRAC safety review on ibuprofen and ketoprofen, EMA highlights the need for epidemiological studies to be conducted in a timely manner to provide adequate evidence on any effect of NSAIDs on disease prognosis for COVID-19. The Agency is reaching out to its stakeholders and is ready to actively support such studies, which could be useful in guiding any future treatment recommendations. EMA will provide further information as necessary and once the PRAC review is concluded.

Sources: EMA, Science Media Centre

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CMY

PAIN Pain • Inflammation • Fever

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CPD

PAIN FOCUS PAIN CPD

Sprains and strains An overview

Lower back pain is the most common type of musculoskeletal pain.

Musculoskeletal pain affects the bones, muscles, ligaments, tendons, and nerves. It can be acute or chronic, localised in one area, or widespread. Other common types include tendonitis, myalgia and stress fractures. Trauma is the most common cause of injury to the musculoskeletal system, and include a direct force, such as a fall or car accident. Other causes of injuries to the musculoskeletal system include repeated wear and tear from daily activities, jerky movements, or sporting activities, such as the recent Comrades Marathon. Musculoskeletal injuries are synonymous with symptoms of pain, swelling, bruising and inflammation.

SPRAINS AND STRAINS Although sprains and strains are common sports injuries, they can just as easily occur during everyday activities such as walking, gardening, cleaning the house, at work or even while sleeping in an awkward position. Tears in ligaments or muscles may be graded as • 1st degree: Minimal (fibers are stretched but intact, or only a few fibers are torn) • 2nd degree: Partial (some to almost all fibers are torn) • 3rd degree: Complete (all fibers are torn)

TENDON INJURIES Tendon tears can be partial or complete. With complete tears, the motion produced by the detached muscle is usually lost.

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Partial tears can result from a single traumatic event (eg, penetrating trauma) or repeated stress (chronically, causing tendinopathy). Motion is often intact, but partial tears may progress to complete tears, particularly when significant or repetitive force is applied.

HEALING Many partial tears in ligaments, tendons, or muscles heal spontaneously. Complete tears often require surgery to

THE

restore anatomy and function. Prognosis and treatment vary greatly depending on the location and severity of the injury.

COMPLICATIONS Serious complications of sprains, strains, and tendon injuries are unusual but may cause permanent limb dysfunction. Acute complications (associated injuries) include the following: • Bleeding: Bleeding (eg, bruising, ecchymoses) accompanies all

significant soft-tissue injuries. • Vascular injuries: Rarely, what appears to be a severe sprain may be a spontaneously reduced dislocation (eg, of the knee), which may be accompanied by a limb-threatening arterial injury. • Nerve injuries: Nerves may be injured when stretched or damaged by associated injuries such as fractures or dislocations or by blunt blows or crush injuries. When nerves are bruised

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References: 1. Waldman HJ. J Pain Symptom Manage 1994; 9(7):434-441. 2. Impact Rx. Script Data – October 2017. Scheduling status: S2 Proprietary name (and dosage form): NORFLEX CO Tablets. Composition: Each tablet contains 35 mg Orphenadrine citrate and 450 mg Paracetamol. Pharmacological classification: A.2.9 (Other analgesics). Reference number: B 1098 [Act 101/1965]; Scheduling status: S2 Proprietary name (and dosage form): NORFLEX Tablets. Composition: Each tablet contains 100 mg Orphenadrine citrate. Pharmacological classification: Category: A.2.10 (Centrally active muscle relaxants). Reference number: H 1612. [Act 101/1965]. Scheduling status: S1 Proprietary name and dosage form: NORFLEX Gel. Composition: Each 100g contains: Benzydamine hydrochloride 3,0g. Pharmacological classification: A3.1 Antirheumatics (anti-inflammatory) agents. Registration number: 32/3.1/0547. Name and business address of applicant: iNova Pharmaceuticals (Pty) Ltd. Reg. No.: 1952/001640/07. 15E Riley Road, Bedfordview. Tel. No.: 011 087 0000. www.inovapharma.co.za. For full prescribing information, refer to the package insert as approved by the MCC (Medicines Control Council). Further information is available on request from iNova Pharmaceuticals. IN2524/18.

MEDICAL CHRONICLE JUNE 2018 45 33 MEDICAL| CHRONICLE

CPD

PAIN FOCUS PAIN CPD

(called neurapraxia), nerve conduction is blocked, but the nerve is not torn. Neurapraxia causes temporary motor and/or sensory deficits; neurologic function returns completely in about 6 to 8 weeks. When nerves are crushed (called axonotmesis), the axon is injured, but the myelin sheath is not. This injury is more severe than neurapraxia. Depending on the extent of the damage, the nerve can regenerate over weeks to years. Usually, nerves are torn (called neurotmesis) in open injuries. Torn nerves do not heal spontaneously and

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Long-term complications include: • Instability: Various ligament injuries, particularly 3rd-degree sprains, can lead to joint instability. Instability can be disabling and increases the risk of osteoarthritis. • Stiffness and impaired range of motion: Stiffness is more likely if a joint needs prolonged immobilisation. The knee, elbow, and shoulder are particularly prone to posttraumatic stiffness, especially in the elderly. • Osteoarthritis: Injuries that result in joint instability predispose to repeated joint stresses that can damage joint

cartilage and result in osteoarthritis.

EVALUATION Diagnosis of sprains, strains, and tendon injuries should include a thorough history and physical examination, which are often sufficient for diagnosis. In the emergency department, if the mechanism of injury suggests potentially severe or multiple injuries. Patients should be checked for fractures and dislocations as well as ligament, tendon, and muscle injuries; sometimes parts of this evaluation are deferred until fracture is excluded. The joint above and below the injured joint should also be examined.

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may have to be repaired surgically. • Compartment syndrome: Rarely, swelling under a cast is severe enough to contribute to compartment syndrome. Tissue pressure increases in a closed fascial space, disrupting the vascular supply and reducing tissue perfusion. Untreated compartment syndrome can lead to rhabdomyolysis, hyperkalemia, and infection. It can also cause contractures, sensory deficits, and paralysis. Compartment syndrome threatens limb viability (possibly requiring amputation) and survival.

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History focuses on the • Mechanism of injury • Past injuries • Timing of pain onset • Extent and duration of pain before, during, and after activity. Clinicians should also ask about use of drugs (eg fluoroquinolones, corticosteroids) that increase the risk of tendon tears. The mechanism (direction and magnitude of force) may suggest the type of injury. However, many patients do not remember or cannot describe the exact mechanism. If a patient reports a deformity that has resolved before being seen by a healthcare professional, the deformity should be assumed to be a true deformity that spontaneously reduced. A perceived snap or pop at the time of injury may signal a ligament or tendon injury (or a fracture). Serious ligamentous injuries usually cause immediate pain; pain that begins hours to days after the injury suggests minor injury.

PHYSICAL EXAMINATION

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References: 1. Norflex® Gel approved package insert, September 2001. 2. Impact Rx. Script Data – February 2018. 3. South African Medicine Price Registry. Database of Medicine Prices. [Online] 2018 May 02 [cited 2018 May 15]; Besemax® Tablet. Each tablet contains orphenadrine citrate 35 mg 4. andDifflam paracetamol 450 2018 mg. Reg. Available at S2 URL: http://www.mpr.gov.za/PublishedDocuments.aspx#DocCatId=21. Gel [cited MayNo. 15];30/2.8/0099. Available from URL: http://www.myvmc.comdrugsdifflam-gel/. For full prescribing information refer to the package insert approved by the medicines regulatory authority.

Scheduling status: S2 Proprietary name (and dosage form): NORFLEX CO Tablets. Composition: Each tablet contains 35 mg Orphenadrine citrate and 450 mg Paracetamol. Adcock Ingram Limited. Reg. No.(Other 1949/034385/06. Bag X69, Bryanston, 2021, [Act 101/1965]; Scheduling status: S2 Proprietary name (and dosage form): NORFLEX Pharmacological classification: A.2.9 analgesics).Private Reference number: B 1098 South Africa. Telephone + 27 11 635 0000. www.adcock.com Tablets. Composition: Each tablet contains 100 mg Orphenadrine201804161076988 citrate. Pharmacological classification: Category: A.2.10 (Centrally active muscle relaxants). Reference number: H 1612. [Act 101/1965]. Scheduling status: S1 Proprietary name and dosage form: Norflex Gel. Composition: Each 100 g contains Benzydamine hydrochloride 3,0 g. Pharmacological classification: A3.1 Antirheumatics (anti-inflammatory) agents. Registration number: 32/3.1/0547. Name and business address of applicant: iNova Pharmaceuticals (Pty) Ltd. Co. Reg. No.: 1952/001640/07. 15E Riley Road, Bedfordview. Tel. No.: 011 087 0000. www.inovapharma.co.za. For full prescribing information, refer to the package insert as approved by the MCC (Medicines Control Council). Further information is available on request from iNova Pharmaceuticals. IN2677/18

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Examination includes: • Vascular and neurologic assessment • Inspection for deformity, swelling, ecchymoses, open wounds, and decreased or abnormal motion • Palpation for tenderness, crepitation, and gross defects in bone or tendon • Examination of the joints above and below the injured area • After fracture and dislocation are excluded (clinically or by imaging), stress testing of the affected joints for pain and instability. If muscle spasm and pain limit physical examination (particularly stress testing), examination is sometimes easier after the patient is given a systemic analgesic or local anesthetic. Or the injury can be immobilised until muscle spasm and pain subside, usually for a few days, and then the patient can be reexamined. Deformity suggests dislocation, subluxation (partial separation of bones in a joint), or fracture. Swelling commonly indicates a

CPD significant musculoskeletal injury but may require several hours to develop. If no swelling occurs within this time, severe ligament disruption is unlikely. Tenderness accompanies nearly all injuries, and for many patients, palpation anywhere around the injured area causes discomfort. However, a noticeable increase in tenderness in one localized area (point tenderness) suggests a sprain (or fracture). Localized ligamentous tenderness and pain when the joint is stressed are consistent with sprain. With some complete muscle or tendon tears, a defect may be palpable in the affected structure. Gross joint instability suggests severe ligamentous disruption (or dislocation, which may have spontaneously reduced). Stress testing is done to evaluate the stability of an injured joint. If you suspect a fracture, stress testing is deferred until x-rays exclude fracture. Bedside stress testing involves passively opening the joint in a direction usually perpendicular to the normal range of motion (stressing). Because muscle spasm during acutely painful injuries may mask joint instability, the surrounding muscles are relaxed as much as possible, and examinations are begun gently, then repeated, with slightly more force each time. Findings are compared with those for the opposite, normal side but can be limited by their subjective nature. Findings can help differentiate between second- and third-degree sprains: • Second-degree sprains: Stress is painful, and joint opening is limited. • Third-degree sprains: Stress is less painful because the ligament is completely torn and is not being stretched, and joint opening is significant. If muscle spasm is severe despite use of analgesia or anesthetic injection, the examination should be repeated a few days later, when the spasm has subsided. Some partial tendon tears escape initial clinical detection because function appears intact. Any of the following suggests partial tendon tears: • Tendon tenderness • Pain when the joint is moved through its range of motion • Dysfunction • Weakness • Palpable defects. Partial tendon tears may progress to complete tears if patients continue to use the injured part. If the mechanism of injury or examination suggests a partial tendon injury or if the examination is inconclusive, a splint should be applied

PAIN FOCUS PAIN CPD

RICE • Patients who have soft-tissue injuries, with or without other musculoskeletal injuries, may benefit from RICE (rest, ice, compression, elevation), although this practice is not supported by strong evidence. • Rest may prevent further injury and speed healing. • Ice and compression may minimise swelling and pain. Ice is enclosed in a plastic bag or towel and applied intermittently during the first 24 to 48 h (for 15 to 20 min, as often as possible). Injuries can be compressed by a splint, an elastic bandage, or, for certain injuries likely to cause severe swelling, • Elevating the injured limb above the heart for the first 2 days in a position that provides an uninterrupted downward path; such a position allows gravity to help drain edema fluid and minimise swelling. • After 48 hours, periodic application of warmth (eg, a heating pad) for 15 to 20 minutes may relieve pain and speed healing. to limit motion and thus the potential for further injury. Subsequent examination, occasionally supplemented with MRI, may further delineate the extent of injury. Attention to certain areas during examination can help detect commonly missed injuries. If physical examination is normal in a joint that patients identify as painful, the cause may be referred pain. For example, patients with a sternoclavicular joint injury may feel pain in their shoulder. Clinicians should always examine the joint above and below the injury.

Diagnosis of sprains, strains, and tendon injuries should include a thorough history and physical examination, which are often sufficient for diagnosis. In the emergency department, if the mechanism of injury suggests potentially severe or multiple injuries.

IMAGING Not all limb injuries require imaging. Many ankle sprains do not require x-rays during the initial evaluation because the probability of finding a fracture that would require a change in treatment is acceptably low. For ankle sprains, explicit, generally accepted criteria for obtaining x-rays can help limit x-rays to patients that are more likely to have a fracture requiring specific treatment. If imaging is needed, plain x-rays are done first. Plain x-rays, which show primarily bone (and joint effusion secondary to bleeding or occult fracture), may be done to check for dislocations and fractures. These do not show direct evidence of sprains but may show abnormal anatomic relationships

that suggest sprains or other soft-tissue injuries. X-rays should include at least 2 views taken in different planes (usually anteroposterior and lateral views). Additional views (eg. oblique) may be done when: • The evaluation suggests fracture and 2 projections are negative. • They are routine for certain joints (eg, a mortise view for evaluating an ankle, an oblique view for evaluating a foot). • Certain abnormalities are suspected. For lateral views of digits, the digit of interest should be separated from the others. MRI can be done to identify soft-tissue injuries, including ligament, tendon, cartilage, and muscle injuries. MRI or CT may also be done to check for subtle fractures.

TREATMENT Serious associated problems, if present, are treated first. Hemorrhagic shock is treated immediately. Injuries to arteries are surgically repaired unless they affect only small arteries with good collateral circulation. Severed nerves are surgically repaired; for neuropraxia and axonotmesis, initial treatment is usually observation, supportive measures, and sometimes physical therapy. Suspected open fractures or dislocations require: • Sterile wound dressings • Tetanus prophylaxis • Broad-spectrum antibiotics (eg, a 2nd-generation cephalosporin plus an aminoglycoside) • Surgery to irrigate and debride them (and thus prevent infection). Most moderate and severe injuries, particularly grossly unstable ones, are immobilised immediately by splinting (immobilisation with a nonrigid or noncircumferential device) to decrease pain and to prevent further injury to soft tissues by unstable injuries. Pain is treated as soon as possible, typically with opioids. Topical nonsteroidal anti-inflammatory drugss (NSAIDs) can provide good levels of pain relief, without the systemic adverse events associated with oral

NSAIDs, when used to treat acute musculoskeletal conditions. Benzydamine hydrochloride is a topical analgesic and NSAID agent used to treat short-term pain and inflammation including acute inflammatory disorders including sprains, strains, muscular pains, nonarthritic inflamed joints and following fractures. It is used to stop pain and swelling at a specific site. This drug is a locally acting analgesic (pain reliever) and anti-inflammatory treatment for the relief of painful inflammatory conditions of the mouth and throat, including mouth ulcers, teething in infants, sore throat, sore tongue or gums, and discomfort associated with dentures or dental work. It is also a short-term treatment for the relief of pain and swelling, including acute inflammatory disorders including sprains, strains, muscular pains, non-arthritic inflamed joints and following fractures. After initial treatment, soft-tissue injuries are treated symptomatically and are immobilised as indicated. Many third-degree sprains and tendon tears require surgical repair.

IMMOBILISATION Immobilisation decreases pain and facilitates healing by preventing further injury. First-degree sprains should be immobilised only briefly if at all. Early mobilisation is best. Mild second-degree sprains are often immobilised with a sling or splint for a few days. Severe second-degree and some third-degree sprains and tendon tears are immobilized for days or weeks, sometimes with a cast. Many 3rd-degree sprains require surgery. Usually, immobilisation is only adjunctive therapy.

References

Web MD. Benzydamine hydrochloride. Accessed 15/05/2018. Cleveland Clinic. https://my.clevelandclinic.org/ health/diseases/14526-musculoskeletal-pain. Accessed 15/05/2018. Merck Manual. professional version: Overview of Sprains and Other Soft-Tissue Injuries. Accessed 15/05/2018. iNova Pharmaceuticals. Norflex Gel consumer leaflet.

MEDICAL CHRONICLE 47 MEDICAL CHRONICLE | JUNE 2018

Guidelines Treating migraine in children PAIN FOCUS

Guidelines treating migraine in children

The American Academy of Neurology (AAN) and the American Headache Society have issued new guidelines on preventing and treating migraine in children. The guidelines, published in Neurology, update the AAN's 2004 recommendations.

an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence.

RESULTS There is evidence to support the e cacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confi dence in the evidence varies between agents. There is high confi dence that adolescents receiving

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Fast, effective relief of pain and fever from1,3,4 Teething Pain • Toothache • Sore Throats • Headaches

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HEY PERFORMED A systematic review of the literature and rated risk of bias of included studies according to the American Academy of Neurology classification of evidence criteria. A multidisciplinary panel developed practice recommendations, integrating findings from the systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence.

evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headachefree at two hours than those receiving placebo. No acute treatments were effective for migraine-related nausea or vomiting; some triptans were effective for migrainerelated phonophobia and photophobia.

early in the attack. Ibuprofen oral solution (10mg/kg) should be the initial treatment Gentle for children and adolescents. Additionally, on adolescents may take triptans, such tummies2 as sumatriptan/naproxen tablets and zolmitriptan nasal spray • For patients who also have substantial nausea and vomiting, offer an antiemetic • Caution patients and their families about medication overuse. For example, ibuprofen should not be used more than 14 days a month and triptans shouldn't be used more than nine days a month.

RECOMMENDATIONS Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, Migraine treatment should aim to choosing the route of administration best suited to the characteristics of the individual achieve fast, complete pain relief, with minimum side effects. Associated migraine attack, and providing counselling RESULTS symptoms like nausea, vomiting, on lifestyle factors that can exacerbate There is evidence to support the efficacy Available in Strawberry Flavour. Sugar Alcohol Free. should also photophobia, and phonophobia migraine, including trigger avoidance and and of the use of ibuprofen, acetaminophen be addressed. In adults, early treatment medication overuse and include: (in children and adolescents), and triptans Contains Paracetamol. References: 1. Wilcock A, Twycross R. Therapeutic reviews: Acetaminophen (Paracetamol). J. Pain Symptom Manag. 2013,46(5):747-757. 2. Goodman & Gilman’s. The of migraine (within less than one hour of • Counsel patients and their caregivers that (mainly inPharmacological adolescents) for the relief of Basis of Therapeutics, 13th ed. Acetaminophen. p696. 3. Panado Paediatric Strawberry Approved package insert March 2002. 4. Van den Anker JN. Optimising the management 20 headache onset) improves pain-free is mostSyrup effStrawberry. ective when given migraine ofpain, although confiIntdence in the S0 Panado® Paediatric fever and pain in children. J Clin Pract 2013;67(178):26-32.treatment Each 5 ml contains paracetamol 120 mg. Reg. No. 35/2.7/0112. For full prescribing rates . information refer to the prescriber information approved by the medicines regulatory authority. Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021, South Africa. Tel. +27 11 635 0000 www.adcock.com. 202001291011650. 14566T

14 OCTOBER 2019 | MEDICAL CHRONICLE

48 MEDICAL CHRONICLE

oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headachefree at two hours than those receiving placebo. No acute treatments were e ective for migraine-related nausea or vomiting; some triptans were e ective for migrainerelated phonophobia and photophobia. RECOMMENDATIONS Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, choosing the route of administration best suited to the characteristics of the individual migraine attack, and providing counselling on lifestyle factors that can exacerbate migraine, including trigger avoidance andmedication overuse and include: • Counsel patients and their caregivers that treatment is most e ective when given early in the attack. Ibuprofen oral solution (10mg/kg) should be the initial treatment for children and adolescents. Additionally, adolescents may take triptans, such as sumatriptan/naproxen tablets and zolmitriptan nasal spray • For patients who also have substantial nausea and vomiting, o er an antiemetic • Caution patients and their families about medication overuse. For example, ibuprofen should not be used more than 14 days a month and triptans shouldn't be used more than nine days a month. Migraine treatment should aim to achieve fast, complete pain relief, with minimum side e ects. Associated symptoms like nausea, vomiting, photophobia, andwith phonophobia should isalso Improved efficacy early treatment be addressed. likely to be seenIninadults, childrenearly andtreatment adolescents migraine less one hour of asofwell. Many(within children andthan adolescents headache onset) improves pain-free oral use and benefi t from nonprescription rates20. Improved e cacy with ibuprofen early analgesics like acetaminophen, treatment is21likely to beare seen children and naproxen .Triptans lessincommonly and adolescents as well. children prescribed in children thanMany in adults, and andalmotriptan adolescents(for usepatients and benefi t from only aged 12 nonprescription oral analgesics like years and older), rizatriptan (for patients acetaminophen, and naproxen21. aged 6–17 years),ibuprofen sumatriptan/naproxen Triptans areaged less commonly prescribed (for patients 12 years and older), in children than in NS adults, and zolmitriptan (for and patients aged 12 only almotriptan (for patientsbyaged years and older) are approved the 12 Food years andAdministration older), rizatriptan (forfor patients and Drug (FDA) use in aged 6–17 years), children. Ergots andsumatriptan/naproxen oral naproxen alone (for patients 12 years and older), have not beenaged studied in children. and zolmitriptan NS (for patients aged 12 years and older) are approved by the Food Source: Oskoui M, Pringsheim T,(FDA) Holler-Managan and Drug Administration for use Yinet al.children. Practice guideline summary: Acutealone treatment Ergots update and oral naproxen of migraine in children and adolescents. Neurology have not been studied in children. 2019,10.1212/WNL.0000000000008095; DOI: 10.1212/WNL.0000000000008095. Source: Oskoui M, Pringsheim T, HollerManagan Y et al. Practice guideline update summary: Acute treatment of migraine in children and adolescents. Neurology 2019,10.1212/ WNL.0000000000008095; DOI: 10.1212/WNL.0000000000008095.

PAIN FOCUS PAIN

MIGRAINE TREATMENT

Migraine continues being an underdiagnosed condition because it is often accompanied by symptoms commonly associated with other causes of facial pain. Many patients visit their GP because of their headache and, in many cases, a proper diagnosis and treatment may take years.

The Revised French Migraine Guideline includes the following pharmaceutical treatments.

ACUTE TREATMENT OF MIGRAINE Two types of treatment can be distinguished: Nonspecific treatments NSAIDs: Naproxen, ibuprofen, ketoprofen and diclofenac. Ibuprofen is approved for the treatment of mild to moderate migraine with or without aura. Other NSAIDs: Do not have specific indications for the acute treatment of migraine. Acetylsalicylic acid (ASS): As monotherapy or in association with metoclopramide. Only the association ASS-metoclopramide has been approved for the symptomatic treatment of migraine and associated digestive problems. Paracetamol as monotherapy: Does not have a specific indication for the acute treatment of migraine. Opioids: It is recommended that opioids are avoided (codeine, opium, tramadol, morphine and other strong opioids), alone or in association, as they may induce drug abuse or even addictive behaviour and can also increase nausea. Specific treatments for migraine attacks Triptans: Are effective against headaches, but also against the associated digestive symptoms as well as phonophobia and photophobia. There are minimal differences in efficacy and tolerance between the triptans, but in practice there is great interindividual variability. Before concluding that a triptan is ineffective, it is recommended that it is tested over at least three attacks, except if there is poor tolerance. A patient who is a nonresponder to one triptan may respond to another. The association sumatriptan and naproxen sodium is more effective than either of the two drugs taken individually. Taking a triptan early when the headache is mild is more effective than taking the triptan when the headache is moderate to severe in intensity. Ergotamine tartrate is approved for the acute treatment of migraine. Dihydroergotamine (pernasal and injectable) via the pernasal route has been approved for the acute treatment of migraine.

Prophylactic treatment As a function of the frequency and intensity of attacks, but also the familial, social and professional handicap caused by the attacks. As soon as the patient uses treatment(s) for attacks more than two days each week, for three months, even in the

case of efficacy, in order to avoid drug abuse. The initiation of prophylactic treatment should be associated with an educational strategy in which it should be explained to the patient that prophylactic treatment will not prevent attacks but will reduce their frequency

and intensity. Keeping a diary of attacks will allow a better appreciation of the efficacy of prophylactic treatment. Reference

Lanteri-Minet M et al. Revised French guidelines for the diagnosis and management of migraine in adults and children.The Journal of Headache and Pain. 2014.

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Doctors and specialists have been prescribing Myprodol® for more than 30 years1 for the effective treatment of mild to moderate pain of inflammatory origin with or without fever. Life should be a journey of joy, not a struggle filled memories. Brufen ®, the original Why change when you with knowpainful it works? ibuprofen, gives your patients effective relief from pain, fever and inflammation so they can get back to living their lives to the full. 1 Reference: 1. Brufen® Retard Tablets Package Insert. Abbot Laboratories, South Africa. 26 June 1991.

Original. Dependable. Since 1987.

S3 BRUFEN RETARD® TABLETS. Each film-coated tablet contains 800 mg of ibuprofen in 1 a sustained-release form. Reg. No.: Y/3.1/0013. S2 & S3 BRUFEN® PAEDIATRIC SUSPENSION. Each 5 ml of suspension contains 100 mg ibuprofen. Reg. No.: Q/3.1/0323. For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority. Further information is available on request from the holder of the registration. Abbott Laboratories S.A. (Pty) Ltd. Abbott Place, 219 Golf Club Terrace, Constantia Kloof, 1709. Tel: (011) 858 2000. Date of publication of this promotional material January 2015. Promotional review number ZAEBFN130093 Reference: 1. Myprodol® Capsules approved package insert, May 1987. MYPRODOL® Capsules. Each capsule contains codeine phosphate 10 mg; ibuprofen 200 mg; paracetamol 250 mg. Reg. No. T/2.8/244. For full prescribing information refer to the package insert approved by the Medicines Regulatory Authority. 202008141051764. Adcock Ingram Limited. Reg. No. 1949/034385/06. Private Bag X69, Bryanston, 2021, South Africa. Tel. +27 11 635 0000. www.adcock.com.

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