The Pain Practitioner - Neuropathic Pain

Integrative Pain Management for Optimal Patient Care

The Pain Practitioner May/June 2017

Neuropathic pain +

Inflammation and our Old Friend Lidocaine Implantable Peripheral Nerve Stimulation Q&A: Biopsychosocial Risk Factors for Spinal Cord Stimulation

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OF PAIN OF RELIEF NUCYNTA® ER is the first and only FDA-approved long-acting opioid designed to control both nociceptive pain and the neuropathic pain associated with diabetic peripheral neuropathy (DPN).

Not an actual patient.

Visit Nucynta.com for more information and to download a NUCYNTA® ER savings card

INDICATIONS AND USAGE Limitations of Use NUCYNTA ER is an opioid agonist indicated for the management of: • Because of the risks of addiction, abuse, and misuse with opioids, • pain severe enough to require daily, around-the-clock, longeven at recommended doses, and because of the greater risks of term opioid treatment and for which alternative treatment overdose and death with extended-release opioid formulations, options are inadequate reserve NUCYNTA ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate• neuropathic pain associated with diabetic peripheral release opioids) are ineffective, not tolerated, or would be neuropathy (DPN) severe enough to require daily, around-theotherwise inadequate to provide sufficient management of pain. clock, long-term opioid treatment and for which alternative treatment options are inadequate.

• NUCYNTA ER is not indicated as an as-needed (prn) analgesic.

NUCYNTA® ER IMPORTANT SAFETY INFORMATION WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning.

• NUCYNTA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow NUCYNTA ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be lifethreatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (5.3).

• Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. (5.4), (7).

Please see additional Important Safety Information, including BOXED WARNING, and Brief Summary on the following pages.

NUCYNTA® ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) CONTRAINDICATIONS NUCYNTA ER is contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected gastrointestinal obstruction, including paralytic ileus • Hypersensitivity (e.g. anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product.

• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse NUCYNTA ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA ER exposes users to the risks of addiction, abuse, and misuse. Because extendedrelease products such as NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).

Abuse or misuse of NUCYNTA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death.

Opioid are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA ER. Life-threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death.

To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential. Overestimating the NUCYNTA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

Neonatal Opioid Withdrawal Syndrome Prolonged use of NUCYNTA ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal

opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Risk from Concomitant Use with Benzodiazepines or Other CNS Depressants Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol.

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA ER with benzodiazepines or other CNS depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA ER is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of NUCYNTA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: NUCYNTA ER treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA ER.

NUCYNTAÂŽ ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Alternatively, consider the use of non-opioid analgesics in these patients.

Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of tapentadol with serotonergic drugs.Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range.

See Warnings and Precautions in full Prescribing Information for a list of symptoms associated with Serotonin Syndrome.

Discontinue NUCYNTA ER if serotonin syndrome is suspected.

Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids.

Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

Severe Hypotension NUCYNTA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients.

There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics).

Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA ER. In patients with circulatory shock, NUCYNTA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA ER in patients with circulatory shock.

Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), NUCYNTA ER may reduce respiratory

drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA ER. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA ER in patients with impaired consciousness or coma.

Risks of Use in Patients with Gastrointestinal Conditions NUCYNTA ER is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The tapentadol in NUCYNTA ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Increased Risk of Seizures in Patients with Seizure Disorders The tapentadol in NUCYNTA ER may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA ER therapy.

Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA ER. In these patients, mixed agonists/ antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.

When discontinuing NUCYNTA ER, gradually taper the dose. Do not abruptly discontinue NUCYNTA ER. Risks of Driving and Operating Machinery NUCYNTA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA ER and know how they will react to the medication.

Risk of Toxicity in Patients with Hepatic Impairment A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA ER in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA ER. Risk of Toxicity in Patients with Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

ADVERSE REACTIONS In clinical studies, the most common (≼10%) adverse reactions were nausea, constipation, vomiting, dizziness, somnolence, and headache.

NUCYNTAÂŽ ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) Select Postmarketing Adverse Reactions Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA ER. Advise patients how to recognize such reactions and when to seek medical attention. Panic attack has also been reported.

DRUG INTERACTIONS Alcohol See BOXED WARNING. Benzodiazepines and Other Central Nervous System (CNS) Depressants See BOXED WARNING. Serotonergic Drugs See Warnings and Precautions.

Monoamine Oxidase Inhibitors (MAOIs) See Contraindications.

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics May reduce the analgesic effect of NUCYNTA ER and/or precipitate withdrawal symptoms. Avoid concomitant use.

Muscle Relaxants See BOXED WARNING and Warnings and Precautions.

Diuretics Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Anticholinergic Drugs The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when NUCYNTA ER is used concomitantly with anticholinergic drugs.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C. NUCYNTA ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome.

Labor or Delivery Opioids cross the placenta and may produce respiratory depression in neonates. NUCYNTA ER is not recommended for use in pregnant women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including NUCYNTA ER, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions.

Lactation Because of the potential for serious adverse reactions including excess sedation and respiratory depression in a breastfed infant, advise patients that breast feeding is not recommended during treatment with NUCYNTA ER.

Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.

Pediatric Use The safety and efficacy of NUCYNTA ER in pediatric patients less than 18 years of age have not been established.

Geriatric Use Elderly patients (aged 65 or older) may have increased sensitivity to tapentadol. In general, use caution when selecting a dosage for an elderly patient.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of NUCYNTA ER slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression.

Hepatic Impairment Use of NUCYNTA ER in patients with severe hepatic impairment is not recommended. In patients with moderate hepatic impairment, dosage reduction of NUCYNTA ER is recommended.

Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment is not recommended.

DRUG ABUSE AND DEPENDENCE See BOXED WARNING OVERDOSAGE In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated.

Cardiac arrest or arrhythmias will require advanced life support techniques.

Please see Brief Summary, including BOXED WARNING, on the following pages.

Š February 2017, Depomed, Inc. All rights reserved. APL-NUCX-0029 Rev. 3

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION This does not include all the information needed to use NUCYNTA ER safely and effectively. See full Prescribing Information for NUCYNTA ER. INDICATIONS AND USAGE NUCYNTA ER (tapentadol) is indicated for the management of: • pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate • neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Limitations of Usage • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations (see Warnings and Precautions), reserve NUCYNTA ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

• NUCYNTA ER is not indicated as an as-needed (prn) analgesic.

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning.

• NUCYNTA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur.

Monitor closely, especially upon initiation or following a dose increase.

Instruct patients to swallow NUCYNTA ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (5.3).

• Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. (5.4), (7).

CONTRAINDICATIONS NUCYNTA ER is contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected gastrointestinal obstruction, including paralytic ileus • Hypersensitivity (e.g. anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product (see Adverse Reactions).

• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (see Drug Interactions).

WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse NUCYNTA ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA ER exposes users to the risks of addiction, abuse, and misuse.

Because extended-release products such as NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present (see Drug Abuse and Dependence).

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA ER. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).

The potential for these risks should not, however, prevent the prescribing of NUCYNTA ER for the proper management of pain in any given patient.

Patients at increased risk may be prescribed opioids such as NUCYNTA ER, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA ER along with intensive monitoring for signs of addiction, abuse, and misuse.

Abuse or misuse of NUCYNTA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death (see Overdosage).

Opioid are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA ER. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the

proper disposal of unused drug (see Patient Counseling Information). Contact the local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status (see Overdosage). Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA ER, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression especially within the first 24-72 hours of initiating therapy with and following dosage increases of NUCYNTA ER. To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential (see Dosage and Administration). Overestimating the NUCYNTA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

Neonatal Opioid Withdrawal Syndrome Prolonged use of NUCYNTA ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (see Use in Specific Populations, Patient Counseling Information).

Risk from Concomitant Use with Benzodiazepines or Other CNS Depressants Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol (see Clinical Pharmacology).

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA ER with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics (see Drug Interactions).

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA ER is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs (see Drug Interactions and Patient Counseling Information).

Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of NUCYNTA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: NUCYNTA ER treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA ER (see Warnings and Precautions).

Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients (see Warnings and Precautions).

Alternatively, consider the use of non-opioid analgesics in these patients.

Monitor such patients closely, particularly when initiating and titrating NUCYNTA ER and when NUCYNTA ER is given concomitantly with other drugs that depress respiration (see Warnings and Precautions).

Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of tapentadol with serotonergic drugs.

Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic

antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) (see Drug Interactions). This may occur within the recommended dosage range.

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that.

Discontinue NUCYNTA ER if serotonin syndrome is suspected.

Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

Severe Hypotension NUCYNTA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) (see Drug Interactions). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA ER. In patients with circulatory shock, NUCYNTA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA ER in patients with circulatory shock.

Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), NUCYNTA ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA ER. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA ER in patients with impaired consciousness or coma.

Risks of Use in Patients with Gastrointestinal Conditions NUCYNTA ER is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The tapentadol in NUCYNTA ER may cause spasm of the sphincter of Oddi.

Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Increased Risk of Seizures in Patients with Seizure Disorders The tapentadol in NUCYNTA ER may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA ER therapy.

Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA ER. In these patients, mixed agonists/ antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms (see Drug Interactions).

When discontinuing NUCYNTA ER, gradually taper the dose (see Dosage and Administration). Do not abruptly discontinue NUCYNTA ER (see Drug Abuse and Dependence).

Risks of Driving and Operating Machinery NUCYNTA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA ER and know how they will react to the medication (see Patient Counseling Information).

Risk of Toxicity in Patients with Hepatic Impairment A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA ER in patients with moderate hepatic impairment (see Dosage and Administration and Clinical Pharmacology). Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA ER. Risk of Toxicity in Patients with Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known (see Clinical Pharmacology).

ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse (see Warnings and Precautions) • Life-Threatening Respiratory Depression (see Warnings and Precautions) • Neonatal Opioid Withdrawal Syndrome (see Warnings and Precautions) • Interaction with Benzodiazepine or Other CNS Depressants (see Warnings and Precautions)

• Serotonin Syndrome (see Warnings and Precautions) • Adrenal Insufficiency (see Warnings and Precautions) • Severe Hypotension (see Warnings and Precautions) • Gastrointestinal Adverse Reactions (see Warnings and Precautions) • Seizures (see Warnings and Precautions) • Withdrawal (see Warnings and Precautions) Clinical Trial Experience Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA ER in Patients with Chronic Pain due to Low Back Pain or Osteoarthritis The most common adverse reactions (reported by ≥10% in any NUCYNTA ER dose group) were: nausea, constipation, dizziness, headache, and somnolence.

The most common reasons for discontinuation due to adverse reactions in eight Phase 2/3 pooled studies reported by ≥1% in any NUCYNTA ER dose group for NUCYNTA ER- and placebo-treated patients were nausea (4% vs. 1%), dizziness (3% vs. <1%), vomiting (3% vs. <1%), somnolence (2% vs. <1%), constipation (1% vs. <1%), headache (1% vs. <1%), and fatigue (1% vs. <1%), respectively.

Please see full Prescribing Information for ADRs occurring in ≥ 1% of patients.

Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA ER in Patients with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy The most commonly reported ADRs (incidence ≥10% in NUCYNTA ER-treated subjects) were: nausea, constipation, vomiting, dizziness, somnolence, and headache.

Please see full Prescribing Information for ADRs occurring in ≥ 1% of patients.

Postmarketing Experience The following adverse reactions have been identified during post approval use of tapentadol.

Psychiatric disorders: hallucination, suicidal ideation, panic attack Serotonin syndrome: Cases of serotonin syndrome, a potentially lifethreatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in NUCYNTA ER. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids (see Clinical Pharmacology).

DRUG INTERACTIONS Clinically Significant Drug Interactions with NUCYNTA ER Alcohol Clinical Impact:

Concomitant use of alcohol with NUCYNTA ER can result in an increase of tapentadol plasma levels and potentially fatal overdose of tapentadol.

Intervention: Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy.

Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Due to additive pharmacologic effect, the concomitant use of Impact: benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.

Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions (5.4)].

Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.

Serotonergic Drugs Clinical The concomitant use of opioids with other drugs that affect Impact: the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions 5.6].

Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

Discontinue NUCYNTA ER if serotonin syndrome is suspected.

Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Monoamine Oxidase Inhibitors (MAOIs) Clinical MAOI interactions with opioids may manifest as serotonin Impact: syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2)].

Intervention: Do not use NUCYNTA ER in patients taking MAOIs or within 14 days of stopping such treatment Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical May reduce the analgesic effect of NUCYNTA ER and/or Impact: precipitate withdrawal symptoms.

Intervention: Avoid concomitant use.

Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Tapentadol may enhance the neuromuscular blocking action of Impact: skeletal muscle relaxants and produce an increased degree of respiratory depression.

NUCYNTA ER (tapentadol) extended-release tablets, CII BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION (continued) Muscle Relaxants (continued) Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of NUCYNTA ER and/or the muscle relaxant as necessary.

Diuretics Clinical Opioids can reduce the efficacy of diuretics by inducing the Impact: release of antidiuretic hormone.

Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Anticholinergic Drugs Clinical The concomitant use of anticholinergic drugs may increase Impact: risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when NUCYNTA ER is used concomitantly with anticholinergic drugs.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome (see Warnings and Precautions).

The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy can occur regardless of the health of the mother or the use of medications.

Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.

Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly (see Warnings and Precautions).

Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psychphysiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. NUCYNTA ER is not recommended for use in pregnant women during and immediately prior to labor. Opioid analgesics, including NUCYNTA ER, can prolong labor.

Lactation Risk Summary There is insufficient/limited information on the excretion of tapentadol in human or animal breast milk. Physicochemical and available pharmacodynamic/toxicological data on tapentadol point to excretion in breast milk and risk to the breastfeeding child cannot be excluded.

Because of the potential for serious adverse reactions including excess sedation and respiratory depression in a breastfed infant, advise patients that breast feeding is not recommended during treatment with NUCYNTA ER. Clinical Considerations Monitor infants exposed to NUCYNTA ER through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.

Pediatric Use The safety and efficacy of NUCYNTA ER in pediatric patients less than 18 years of age have not been established.

Geriatric Use Of the total number of patients in Phase 2/3 double-blind, multiple-dose clinical studies of NUCYNTA ER, 28% (1023/3613) were 65 years and over, while 7% (245/3613) were 75 years and over. No overall differences in effectiveness or tolerability were observed between these patients and younger patients.

Elderly patients (aged 65 or older) may have increased sensitivity to tapentadol. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of NUCYNTA ER slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression (see Warnings and Precautions).

Hepatic Impairment Use of NUCYNTA ER in patients with severe hepatic impairment (ChildPugh Score 10-15) is not recommended. In patients with moderate hepatic impairment (Child-Pugh Score 7 to 9), dosage reduction of NUCYNTA ER is recommended (see Dosage and Administration).

Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) is not recommended.

DRUG ABUSE AND DEPENDENCE Controlled Substance NUCYNTA ER contains tapentadol, a Schedule II controlled substance.

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| T HE PA I N P R AC T I TI O NE R | M AY / J U N E 2 0 1 7

Abuse NUCYNTA ER contains tapentadol, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone. NUCYNTA ER can be abused and is subject to misuse, addiction, and criminal diversion (see Warnings and Precautions).

The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse.

All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers, and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

NUCYNTA ER, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of NUCYNTA ER NUCYNTA ER is for oral use only. Abuse of NUCYNTA ER poses a risk of overdose and death. The risk is increased with concurrent use of NUCYNTA ER with alcohol and other central nervous system depressants.

With intravenous abuse the inactive ingredients in NUCYNTA ER can result in local tissue necrosis, infection, pulmonary granulomas, embolism and death, and increased risk of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Dependence Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

NUCYNTA ER should not be abruptly discontinued (see Dosage and Administration). If NUCYNTA ER is abruptly discontinued in a physicallydependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms (see Use in Specific Populations).

OVERDOSAGE Clinical Presentation Acute overdosage with NUCYNTA ER can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed.

Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques.

© May 2017, Depomed, Inc. All rights reserved. APL-NUCX-0249

The Pain Practitioner MAY/JUNE 2017

To access the virtual magazine, go to newsstand.aapainmanage.org

PAGE 11

10 NOTES FROM THE FIELD FDA Gets it Right

By Bob Twillman, PhD, FAPM, Executive Director 11 EDITORIAL Clinician Suicide

By W. Clay Jackson, MD, DipTh, Editor-in-Chief 12 ANNUAL MEETING/EDUCATION Pre-conference Sessions

PAGE 14

13 ADVOCACY Federal Policies and Initiatives Affecting Integrative Pain Care

By Amy Goldstein, MSW, Director, State Pain Policy Advocacy Network 14 Neuropathic Pain, Inflammation, and our old Friend Lidocaine

By Don H. Bivins, MD

PAGE 15

15 Implantable Peripheral Nerve Stimulation for the Treatment of Chronic Lower Extremity Neuropathic Pain: A Salvage Procedure Following Failed Nerve Decompression

By Guido A LaPorta, DPM, MS, FACFAS, Louis V. De Fazio, DPM, and Felicia Bock, DPM, CWS 19 Q&A: Biopsychosocial Risk Factors for Spinal Cord Stimulation

By Daniel Bruns PsyD, and John Mark Disorbio, EdD

PAGE 19

And More, on the Web...

We Have a new Website!

Our website was redesigned to make it easier to find the newest research, information and educational opportunities about integrative pain management.

The URL, www.integrativepainmanagement.org, reinforces this mission by emphasizing our focus on, and commitment to, integrative pain management.

Academy of Integrative Pain Management

www.integrativepainmanagement.org

ACADEMY BOARD OF DIRECTORS President Joanna Katzman, MD, MSPH Past President Robert A. Bonakdar, MD, FAAFP Vice President W. Clay Jackson, MD, DipTh Secretary Paul Christo, MD, MBA Treasurer Kevin T. Galloway, BSN, MHA, Colonel, US Army (Retired) Directors-at-Large Alfred V. Anderson, MD, DC George D. Comerci, Jr, MD, FACP John Garzione, DPT Christian D. González, MD Michael Kurisu, DO, ABIHM Joseph Matthews, DDS, MSc Liaison to the Board Maggie Buckley

STAFF AND CONSULTANTS Executive Director Robert Twillman, PhD, FAPM Director of the State Pain Policy Advocacy Network (SPPAN) Amy Goldstein, MSW Assistant Director of Education Cathleen Coneghen SPPAN Assistant Director for Legislative and Regulatory Affairs Katie Duensing, JD Member Services Manager Whitney O’Donnell Account Managers Rosemary LeMay Professional Development Project Manager MacKenzie Davis Content Consultant Debra Nelson-Hogan

THE PAIN PRACTITIONER STAFF AND CONSULTANTS Editor-in-Chief W. Clay Jackson, MD, DipTh Editor Debra Nelson-Hogan Advertising and Sales Leslie Ringe Managing Editor Cathleen Coneghen Clinical Editor Christine Rhodes, MS Art Director Peter McKinley, Pak Creative Copy Editor Rosemary Hope

Features of the new and improved website include: •

More options for you to network and connect with other AIPM members in our Member Portal.

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The Pain Practitioner is published by the Academy of Integrative Pain Management, P: 209-533-9744, Email: aapm@integrativepain.org, website: www.integrativepainmanagement.org.

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The Pain Practitioner is published by the Academy of Integrative Pain Management solely for the purpose of education. All rights are reserved by the Academy to accept, reject, or modify any submission for publication.

The opinions stated in the enclosed printed materials are those of the authors and do not necessarily represent the opinions of the Academy or individual members. The Academy does not give guarantees or any other representation that the printed material contained herein is valid, reliable, or accurate. The Academy of Integrative Pain Management does not assume any responsibility for injury arising from any use or misuse of the printed material contained herein. The printed material contained herein is assumed to be from reliable sources, and there is no implication that they represent the only, or best, methodologies or procedures for the pain condition discussed. It is incumbent upon the reader to verify the accuracy of any diagnosis and drug dosage information contained herein, and to make modifications as new information arises.

All rights are reserved by the Academy to accept, reject, or modify any advertisement submitted for publication. It is the policy of the Academy to not endorse products. Any advertising herein may not be construed as an endorsement, either expressed or implied, of a product or service.

NOTES FROM THE FIELD

FDA Gets it Right

By Bob Twillman, PhD, FAPM, Executive Director

I recently was asked by the US Food and Drug Administration (FDA) to participate in a workshop it held regarding a new opioid Risk Evaluation and Mitigation Strategy (REMS) program. I was one of several representatives from professional societies, all of whom were asked to advise FDA on how best to proceed in revising the existing REMS for extended release/long acting (ER/LA) opioids. I’m pleased to say that I’ve finally found a government agency that appears to be getting it right, in terms of the type of education needed to enhance the safety of opioid prescribing.

A year ago, FDA held an Advisory Committee meeting to examine the results of the existing ER/LA REMS and to obtain advice about how it should be modified.

It was apparent at that time that the ER/ LA REMS has been a colossal failure: the number of prescribers completing the training didn’t meet the goals; the effectiveness of the program in changing the target behaviors was completely unmeasurable; and the amount of money diverted into that program, and away from effective education as determined by the needs assessments of organizations like ours, was tremendous. I called it “a regulatory triple play.”

I advised FDA that any revision to the opioid REMS needed to include the following: education about all opioids, not just the ER/LA products; education aimed at the entire pain management team, not just prescribers; and education about pain management, not just about one group of medications. I also suggested that FDA might need to make this education mandatory in order to reach the number of prescribers they were targeting.

They seem to have listened, because much of what I suggested is in the proposed revision under consideration.

I’ve previously written here that, “If all you have is a hammer, every problem looks like a nail”. For too long, many prescribers have felt that they had only one tool—the hammer of opioids. That’s why so many patients have been getting hammered with them (pun intended). And what did FDA do? It designed an ER/LA REMS program that taught prescribers more about hammers!

Now, FDA is proposing a REMS program that goes beyond just teaching

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prescribers about ER/LA opioid medications. Their new blueprint (found at http:// bit.ly/2qb5hJk) is more comprehensive, and teaches about pain management, not just about opioid monotherapy. The new blueprint would require that new REMS programs teach the basics of pain management, including definitions and mechanisms of pain and assessing patients in pain. It then lists a substantial number of topics under the heading of creating a pain treatment plan, including: the basic components of an effective treatment plan; use of nonpharmacologic therapies; general principles of pharmacologic therapy (not just opioids, but non-opioids as well); management strategies for patients using opioid analgesics; and an addiction medicine primer. Now, that’s educating prescribers about the whole toolbox!

Of course, we still have the challenge of figuring out how patients pay for using the drill, saw, screwdriver, etc., and that was pointed out at the FDA workshop.

While there was universal praise at the workshop for the topics covered in this draft blueprint, and for the stated intent of FDA to teach treatment teams instead of just prescribers, one topic split the participants right down the middle: the issue of whether this training should be mandatory, voluntary, or something in between.

Organizations representing health care providers generally argued against mandatory education, while organizations representing people with pain argued for mandatory education. Many, myself

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included, expressed concern that requiring education this extensive might lead some prescribers to opt out of opioid prescribing—by declining the Schedule II portion of their DEA registration, but keeping the Schedule III-V portions.

Even voluntary policies such as the CDC guideline seem to be driving prescribers, especially primary care providers, to stop prescribing opioids, sometimes abandoning patients who have benefitted from them for years. When you consider that the proposed blueprint would likely require five or six hours to teach (as compared to two or three for the current REMS), there would be significant motivation for prescribers to opt out.

I didn’t take a firm position on the mandatory vs. voluntary issue. I can see both sides of the argument. I worry that a voluntary program will result in an even lower number of “completers,” while a mandatory program will lead to increased “opting out.” I suggested that what I’d really like to see is an incentive for completing the program: perhaps reduced malpractice insurance rates or license renewal fees, or improved reimbursement under Medicare and Medicaid for those who complete the program. Incentivizing completion would reward those who are already motivated, and it might move those who are “on the fence” about completing the training toward doing so.

We’ll soon be submitting comments to FDA on the proposed blueprint, but I can say with some confidence that they will likely be minimal, and more focused on the mechanics of implementing this program than on the content of the blueprint.

Because, as I said at the start, I think FDA might have gotten this one right! ❏ Bob Twillman, PhD, is the executive director for the Academy of Integrative Pain Management.

Dr. Twillman is responsible for overseeing federal and state pain policy developments and advocating for those supporting an integrative approach to managing pain. He also serves as Chair of the Prescription Monitoring Program Advisory Committee for the Kansas Board of Pharmacy.

EDITORIAL

Clinician Suicide W. Clay Jackson, MD, DipTh, Editor-in-Chief

It’s a number that I can’t shake; it keeps floating back to my mind, over and over— 400. Four hundred families, left to question why, and grieve in a particularly complicated and difficult way.

Four hundred practices, destroyed in a single moment. Four hundred communities, left with a gap where a healer stood. Four hundred lives—that’s how many clinicians we lose to suicide annually (and that figure accounts for just physicians and surgeons) (1).

Four hundred is a sobering number, but it’s likely too low to tell the true story of clinician suicide. Add in the untimely losses of nurse practitioners, pharmacists, physical therapists, chiropractors, dentists, and other professionals, and the scope of the tragedy of clinician suicide shifts from individual tragedy to the level of a public health crisis: it is estimated that over a million patients per year lose their clinician to suicide (2).

As with any group of persons vulnerable to depression, clinicians need the individual and systematic support that can help alleviate suffering and prevent loss of life. However, though clinicians share some risk factors for suicide with the general population, and would therefore likely benefit from general strategies to promote mental wellness, clinician suicide is distinct in a number of ways. The key to understanding those differences is to remember the premium value placed by general society, the health care system, and the individual on the professional role of the clinician. It is when this professional role is threatened that clinicians are often at high risk of suicide.

Consider the risk factors for suicide in the general population that do not predict clinician suicide: conflict with a current or former intimate partner, other relational conflict, physical health problem, financial or legal trouble, a recent crisis, death of a family member, or suicide of a family member within the past five years (3). What are the data telling us? That we as clinicians are really, really good at surviving crises, so long as we get to occupy the role we’ve been so conditioned to play, and with which we’ve come to identify so closely— the role of the trusted professional.

When that professional role is threatened, however, by patient complaints

(4) or by workplace conflict (5), the risks for clinician suicide rise significantly. It’s a perfect trap—we are resilient through external challenges because we’ve been culturally and professionally conditioned to function as superheroes who cure what ails the world. But if the stress of maintaining that role is compounded by the fear of losing it, we clinicians view that circumstance as an existential threat, and often succumb to thoughts of self-harm.

The cross-sectional incidence of clinician depression is high—approximately one in four (6). Many of us (nearly half) struggle with feelings of burnout (7). And we’re reluctant to seek help, fearing loss of reputation, discrimination by payer panels and certification bodies, and being “exposed” as someone who somehow is just not “tough enough to take it” in the rough-and-tumble world of superheroism (8). There are strategies to avoid the perfect trap of role threatening and burnout, however, and simple steps of reaching out, getting help, and maintaining mental health can be ways forward.

Here at the Academy, we care deeply not only for patients, but for the unique challenges that clinicians face. Not least among those challenges is remaining well ourselves; if we can’t remain physically, emotionally, and spiritually healthy, how can we assist others in their journey toward wellness? At this fall’s national meeting in San Diego, I’ll be hosting a plenary session that I hope will truly be “like no other.” I’m going to present a deeper dive into the data that I’ve summarized here, but then I’m going to share some personal stories of risk mitigation that have helped me remain a successful clinician. I’m no superhero, for sure. But together, we’ll share some techniques for wellness promotion that can help us be part of super teams.

My goal for our time together? Let’s leave stronger, more confident, and more aware of how we can recognize mental health vulnerabilities in ourselves, our colleagues, and our patients. Let’s learn some simple techniques and carry away some simple tools to empower us to remain at our best. Our patients, and our families, deserve it.

Four hundred. It’s too high. Way too high. And your Academy is doing something about it. Help us make that number disappear. ❏

400 W. Clay Jackson, Editor-in Chief, is clinical assistant professor of family medicine and psychiatry at the University of Tennessee College of Medicine in Memphis, Tennessee, where he maintains a private practice in family and palliative medicine. He is also the medical director of Comprehensive Primary Care, and of Methodist Hospice and Palliative Services. Dr. Jackson is the associate fellowship director of palliative medicine at the University of Tennessee College of Medicine.

References 1. Jackson WC, Jain R, Jain S. Clinician suicide: when the healers are mortally wounded. Paradigm. 2016 20(3):12.

2. Wible PL (2014). Physician suicide 101: Secrets, lies, and solutions. www.medscape.com/viewarticle/834434.

3. Gold KJ, Sen, A, Schwenk, TL. Details on suicide among U.S. physicians: Data from the National Violent Death Reporting System. Gen Hosp Psychiatry. 2013. 35(1):45-49. doi: 10.1016/j. genhosppsych.2012.08.005. Epub 2012 Nov 2.

4. Bourne T, Wynants L, Peters M, et al., The impact of complaints procedures on the welfare, health and clinical practise of 7,926 doctors in the UK: a cross-sectional survey.

BMJ Open. 2015;5:e006687. doi: 10.1136/ bmjopen-2014-006687 5. Lindfors PM, Meretoja OA, Luukkonen A, Elovainio MJ, Leino TJ. Suicidality among Finnish anaesthesiologists. 2009.

Acta Anaethesiol Scand. 2009. 53(8):1027-1035. doi: 10.1111/j.1399-6576.2009.02014.x 6. Compton MT, Frank E, Mental health concerns among Canadian physicians: results from the 2007-2008 Canadian Physician Health Study. 2011. Comp Psychiatry. 52(5):542547. doi: 10.1016/j.comppsych.2010.10.002 7. Peckham, C. 2015. Physician Lifestyle Report. www.medscape.com/features/slideshow/lifestyle/2015/psychiatry 8. Adams EF, Lee AJ, Pritchard CW, White RJE. 2010. Int J Soc Psychiatry. 56(4):359-370. doi: 10.1177/0020764008099123

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ANNUAL MEETING/EDUCATION

Pre-conference Sessions 9:00am – 4:30pm, October 19

AIPM pre-conference courses offer attendees a “deep dive” day learning about one focused topic. In addition to earning 6 CME/CEU credits, attendees will receive a certificate of completion that acknowledges the hours of study on each topic. For more information, see www.integrativepainmanagement.org/page/PreMeetingSessions.

Certificate in Nutritional Pain Management Workshop (CNPM) Chaired by Robert A. Bonakdar, MD, and Nancy Cotter, MD, this practical clinical program will explain the importance of food as a pain management intervention, including the five following components necessary in a diet for those in pain and how to incorporate this vital intervention into your practice: initiating a specialized diet for specific pain conditions; antiinflammatory diet; elimination diet; role of omega-3; and role of herbal supplements in pain management.

Prescribing Opioids for Chronic Pain: Best Practices in the Current Environment This six-hour program will provide education on the optimal management of chronic pain, particularly using opioids appropriately and managing patients’ risk for harm. Pain expert Paul Christo, MD, will discuss the elements of appropriate opioid prescribing and monitoring for chronic pain and engage the program attendees in interactive discussions of two illustrative case studies. Jen Bolen, JD, will discuss the legal and regulatory perspective on opioid prescribing and will discuss how clinicians can best protect themselves and their practices from regulatory action and litigation.

Empowering Patients with Integrative Management of Chronic Centrally Sensitized Pain Using Autonomic Self-Regulation Learn how Autonomic Self-Regulation (ASR) empowers patients to manage centrally sensitized chronic pain, and about the benefits that this intervention has for pain reduction. This course will explain how heart rate variability (HRVB) brings about “left foot braking at the sino-atrial node,” and attendees will learn about the empirically measurable benefit, which this integrative, clinical intervention has for pain reduction.

Don’t miss our outstanding keynote, plenary and break out sessions covering all aspects of integrative pain management.

Check out the full program and registration packages at http://www.integrativepainmanagement.org/page/annualmeeting.

What’s in Store for You at

Our 28th Annual Meeting October 19-22 The newest, evidencebased, integrative approaches to pain management

Network with 1,000 pain professionals for a team-based approach to pain care

Focused, 30-minute educational sessions and practical workshops for your practice

Opportunities to earn a Certificate in Nutritional Pain Management

How pain practitioners can help combat the opioid epidemic

Game-changing pain management technology demonstrations

Register today! http://www.integrativepainmanagement.org/event/2017

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ADVOCACY

Federal Policies and Initiatives Affecting Integrative Pain Care

By Amy Goldstein, MSW, Director, State Pain Policy Advocacy Network

In recent years, many federal initiatives have focused on addressing the dual public health challenges of opioid misuse and abuse and inadequately treated chronic pain. Below is a summary of some of these policies and initiatives that relate to the advancement of integrative pain care.

Agency/ Branch

Program

Summary

AHRQ

Systematic review for nonpharmacological treatments for pain

The Agency for Healthcare Research and Quality proposed key questions for a systematic review on noninvasive, nonpharmacological treatment of chronic pain. The purpose of this review was to assess the effectiveness and safety of nonpharmacological treatments for five chronic pain conditions: low back pain, neck pain, osteoarthritic, fibromyalgia, and tension type headache. Results should be available in late 2017.

CMS

Opioid misuse strategic plan

The Centers for Medicare & Medicaid Services effort includes four priority areas: 1) Implement more effective person-centered and population-based strategies; 2) Expand naloxone use, distribution, and access, when clinically appropriate; 3) Expand screening, diagnosis, and treatment of opioid use disorders; and 4) Increase the use of evidence-based practices for acute and chronic pain management. View the full plan at: https://www.cms.gov/Outreach-and-Education/Outreach/Partnerships/Downloads/CMS-Opioid-MisuseStrategy-2016.pdf

DoD/VA

Evidence-based therapies

The Department of Defense and the Veterans Health Administration have recognized chiropractic and osteopathic manipulation, acupuncture, massage therapy, biofeedback, and yoga as effective treatments for chronic pain, including them in their pain management guidelines and covering the services at DoD/VHA facilities.

NIH/DoD/ VA

Collaboratory Funding Initiative

The National Institutes of Health, Department of Defense, and Veterans Affairs have announced the Pain Management Collaboratory Funding Initiative. Find more at: https://nccih.nih.gov/research/blog/partnering-on-pain

Congress

Comprehensive Addiction and Recovery Act (CARA), passed July 2016

Comprehensive Addiction and Recovery Act of 2016, S. 524 bill passed as the first major federal legislation in 40 years, and the most comprehensive effort undertaken, to address the opioid epidemic.

Many CARA Sections, such as 101, 102, 108, 702, 912, 922, 931-33, have the opportunity to be broadened to additionally address the importance of integrative pain care.

CDC

Guidelines for Prescribing Opioids for Chronic Pain, released March 2016

The Centers for Disease Control and Prevention issued this guideline for primary care providers who are prescribing opioids outside of active cancer treatment, palliative care, and end-of-life care.

When determining when to initiate or continue opioids for chronic pain, a key recommendation states, “non-pharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain.”

Congress/ HHS

ECHO Act passed December 2016

Congress passed the Expanding Capacity for Health Outcomes (ECHO) Act, S. 2873, authorizing the Department of Health and Human Services to study the Project ECHO model. Project ECHO programs link expert specialist teams with primary care clinicians in local communities. In this way, primary care doctors, nurses, and other clinicians learn to provide specialty care to patients in their own communities, expanding access to high quality health care in traditionally underserved areas.

FDA

Public comment July 10; Proposed changes to education blueprint

On May 10, the U.S. Food and Drug Administration released proposed changes to its blueprint for educating health care providers about treating pain. The FDA will take public comment through July 10.

This updated blueprint is part of a strategy the FDA rolled out in 2011 to address prescription medication abuse. The FDA required opioid manufacturers to provide education for health care providers who prescribe their pain medications—but didn’t include mention of acupuncture or chiropractic care in its initial blueprint.

NIH IPRCC

National Pain Strategy, released March 2016

The Interagency Pain Research Coordinating Committee (created by HHS) released the National Pain Strategy in March 2016. The NPS is the federal government’s first coordinated interagency plan to achieve a system of effective, safe, high-quality, evidence-based pain care in the U.S. (see summary here). Under Thomas Novotny, MD, the Office of the Assistant Secretary for Health has assembled a Principals’ Coordinating Council and Implementation Work Groups.

NIH

Out-of-pocket expenses for integrative health care

According to the National Institutes of Health, Americans spent $30.2 billion in out-of-pocket costs for integrative health care approaches during a one-year period. These findings came from an analysis by the National Center for Complementary and Integrative Health and the CDC, based on data from a special supplement on use of complementary health approaches to the 2012 National Health Interview Survey.

Congress

21st Century Cures Act, passed December 2016

After a three-year journey through Congress, the 21st Century Cures Act has been signed and allocates $4.8 billion to the National Institutes of Health to fund the Precision Medicine Initiative, the BRAIN Initiative, and the Cancer Moonshot.

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NEUROPATHIC PAIN, INFLAMMATION, AND OUR OLD FRIEND LIDOCAINE

Neuropathic Pain, Inflammation, and our old Friend Lidocaine

By Don H. Bivins, MD

It is no great revelation that physical pain comes to the sufferer’s awareness when the pain signal has traversed the neural circuit from the point of painful stimulus to the cerebrum’s sensory cortex and on to the limbic and frontal centers. Whatever and wherever the stimulus is that triggered the pain signal, the same complex interaction for transduction, spike initiation, and action potential propagation happens in non-injured tissues.

In the naive tissue, a mechanical or a chemical stimulus creates the electrical impulse. The initial step of transduction involves many proteins native to the uninjured nociceptor. Some of these are the transient receptor potential (TRP) channels, the acid sensing ion channel type 3 (ASIC-3), and the voltage-gated calcium channels. Nociceptors also possess receptors for inflammatory mediators such as G-protein coupled receptors (GPCRs), tyrosine kinase receptors (TRK), and cytokines.

When these proteins and receptors interact normally, the simple pain impulse makes its journey toward the cerebrum, the sufferer removes the offended body part from the stimulus (if possible), and the pain resolves.

The narrative for the injured tissue, though, differs drastically.

From the point of painful stimulus, if tissue injury has occurred, the entire sequence for nociceptor signaling, transduction, etc., is altered.

These alterations may appear only for a season of time and then healing ensues. The pain may last for hours or weeks but resolves. On the contrary, in selected situations, the injury may create permanent changes in the neural pathway and its signaling; consequently, a decree to the sufferer that the pain will endure beyond reason.

Tissue may be injured by an item as simple as a bee sting, or, as we more often see at our Level I Trauma Center, limbs are mangled and chests receive blunt trauma with forces that collapse thoracic cages. Within the injured tissue the consequence at the microscopic level is the same whether the injury is mild or severe—it just varies in degree. We generally refer to this response to injury as “inflammation.” The latter process intends to isolate the offending agent and remove the injured tissue.

As mentioned above, nociceptors possess receptors for inflammatory mediators. When the surrounding tissue becomes inflamed, proinflammatory substances are released from cells that lie within those tissues, or from cells that are summoned

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to the area (leukocytes, monocytes, etc.). Chemokines such as tumor necrosis factor-α (TNF-α), interleukins 1 and 8 (IL-1, IL-8), and lipopolysaccharide are released. Leukocytes, now groomed for their phagocytic function, release lysosomal enzymes, free radicals, and an army of other inflammatory mediators (including prostaglandin E2 and nerve growth factor).

As this chemical milieu is rapidly composting in the background, fascinating adjustments are developing in the neural receptors on the peripheral nerves that lie within the injured tissue. The nociceptive terminals become more sensitive to noxious stimuli, the neuronal membrane is more easily depolarized, and the density of several transducers changes. K+ channels decrease in density and in their ability to produce a spike initiation.

There is an increase in the number and density of voltage-gated calcium channels (VGCC) such as CaV3.2, inward rectifying cation channels (HCN), and the voltagegated sodium channels (Na V1.6, NaV1.7, NaV1.8, and NaV1.9). These changes in channel density are accompanied by changes in channel excitability and threshold for discharge (1). Growing evidence supports the concept that sodium channel proliferation and hyperactivation after nerve injury result in ectopic discharges, manifesting clinically as chronic neuropathic pain.

The term “neuropathic pain” is most often reserved for patients who have had the chronic pain for at least three months, with the characteristic descriptors of sharp, knifelike, electric, jolting, burning, tingling, and shooting.

The reality is that these same descriptors are reported by the patient who has recently experienced tissue injury, such as with an acutely herniated disc or the severance of a peripheral nerve in an industrial accident. If the tissue injury is fresh, the inflammatory cascade leads to the increase of neuronal channels and receptors, and the increased excitability of the neurons. If the inflammation leads to appropriate healing of the nerve and surrounding tissue, then the pain gradually resolves. However, if the inflammatory changes do not diminish but instead continue to irritate the surrounding tissues, and if the neuronal channels and receptors do not heal, then the nerve spontaneously maintains a level of excitability and firing threshold that clinicians see as allodynia, hyperalgesia, and the typical neuropathic pain.

NEUROPATHIC PAIN, INFLAMMATION, AND OUR OLD FRIEND LIDOCAINE When treating the acute injury, the clinician will recognize the presence of nerve injury. Medications most often chosen to treat acute pain are opioids, which can be effective in reducing the pain arising from acute nerve injury, somewhat because the opioid receptors are sensitized at tissue injury to a lower response threshold. In other words, whereas opioids are generally not thought to be effective in chronic neuropathic pain, the opioids can be effective in acute nerve-injured pain due to the hyperresponsiveness of the opioid receptor in the acutely injured state.

Clinicians will also often employ a steroid agent or a nonsteroidal antiinflammatory (NSAID) drug in acute tissue injuries to reduce the potentially negative impact of the inflammatory cascade. This is a logical selection, as this will provide some control over the degree of inflammation occurring while also providing pain reduction.

But is there a different treatment approach that might be preferable? There are many opioids from which to choose, and we know that patients show great variation in their response curve to different opioids. Sometimes we must work our way through several selections even in the acutely injured state before finding one that is efficacious. And the effect of the steroid or the NSAID is unpredictable. They may be quite effective in reducing the brunt of the inflammation without significantly impacting the level of pain. Is there one medicine that can work in both the acute and the chronic pain states and that can reduce both inflammation and pain?

Lidocaine is an amide of the local anesthetic class. The local anesthetics are sodium channel blockers and have been shown for decades to have pain-relieving properties. Each reader of this article has probably been the recipient of lidocaine’s benefit as your sodium channels were blocked locally (at the point of the painful stimulus) for dental extractions or for the placement of sutures. Systemic lidocaine was reported as having analgesic effects in 1962 by Bartlett and Hutaserani in treating postoperative pain. In 1998, Groudine, et al., reported reduced postoperative pain and reduced length of hospital stay with the use of systemic lidocaine (2).

Kosharskyy, et al., list in table form the several studies that have been performed in which systemic lidocaine is shown to be superior to placebo in central neuropathic pain, peripheral neuropathic pain, postherpetic neuralgia, peripheral nerve injury, and complex regional pain syndrome (CRPS) (2). Enhanced recovery after surgery (ERAS) protocols at many hospitals today allow the surgeon to select systemic lidocaine as one of the agents to be administered perioperatively for acute pain control.

Thus, the literature supports the use of local and systemic lidocaine for pain reduction or relief. But, is there literature to support lidocaine’s effectiveness as an antiinflammatory agent?

Cassuto, et al., summarize the antiinflammatory effects of lidocaine as: 1) dose-dependent and reversible inhibition of leukocyte adhesion; 2) dose-dependent and reversible reduction of leukocyte motility from within to outside the vessel wall; 3) inhibition of phospholipase D, and thus reduced leukocyte phagocytosis; 4) reduction of the activity of the enzyme phospholipase A2, thus reducing the release of inflammatory mediators of the eicosanoid class; 5) reduction of prostaglandin biosynthesis; 6) inhibition of thromboxane B2, thus reducing platelet aggregation; 7) inhibition of leukotriene release; 8) inhibition of histamine release; 9) reduction in the production of nitric oxide free radical formation; and 10) inhibition of release or secretion of IL-1, IL-1ß, and IL-8 (3).

Piegeler, et al., demonstrated that lidocaine blocked inflammatory TNF-α and thus reduced endothelial nitric oxide synthase (4).

At Carilion Clinic, systemic lidocaine has now been used effectively in acute nerve-injured and in chronic neuropathic pain

states. We have also used it successfully in acute visceral pain disorders, acute and chronic ischemic pain states, acute postoperative pain, and in sickle cell disease crises. In all cases, the lidocaine is reducing the neuronal transmission of pain signals by blocking sodium channels. In at least the acute, but possibly also some chronic pain states, I believe the lidocaine also is serving as an antiinflammatory agent, which also effectively serves to reduce pain transmission. ❏ Don H. Bivins, MD, is the director of inpatient pain management at the Carilion Clinic in Roanoke, Virgina.

References 1. Gold MS, Gebhart GF. Peripheral pain mechanisms and nociceptor sensitization. In: Bonica’s Management of Pain. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010:24-34.

2. Kosharskyy B, Almonte W, Shaparin N, Pappagallo M, Smith H. Intravenous infusions in chronic pain management. Pain Physician. 2013;16:231-249.

3. Cassuto J, Sinclair R, Bonderovic M. Anti-inflammatory properties of local anesthetics and their present and potential clinical implications. Act Anaesthesiol Scand. 2006;50:265-282.

4. Piegeler T, Votta-Velis EG, Bakhshi FR, et al. Endothelial barrier protection by local anesthetics: ropivacaine and lidocaine block tumor necrosis factor-α-induced endothelial cell Src activation.

Anesthesiol.2014;120:1414-1428.

For more details and data on this topic, see Dr. Bivins’ presentation at the AIPM Annual Meeting in San Diego, October 19-22, 2017.

Thank you

to our Corporate Council Members!

Academy of Integrative Pain Management CORPORATE COUNCIL MEMBERSHIP Contact sales@integrativepain.org or 209-533-9744.

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| VOLUME 27, NUMBER 3 |

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IMPLANTABLE PERIPHERAL NERVE STIMULATION

Implantable Peripheral Nerve Stimulation for the Treatment of Chronic Lower Extremity Neuropathic Pain: A Salvage Procedure Following Failed Nerve Decompression

By Guido A. LaPorta, DPM, MS, FACFAS, Louis V. De Fazio, DPM, and Felicia Bock, DPM, CWS Chronic pain is a major health care concern in the United States.

A 2010 internet-based survey found that 30.7% of participants suffered from chronic pain. Of these, 25% had pain associated with the joints of the foot, and 27% had chronic, non-joint pain associated with the legs and feet (1).

Chronic pain affects normal activities of daily living, and has financial and emotional repercussions. The national cost of pain ranges from $560 to $635 billion annually, including both direct health care and lost productivity costs (2). Chronic pain also has a psychological and emotional cost, with many patients experiencing anxiety, fear, anger, depression, or cognitive dysfunction.

As surgeons, we are capable of controlling perioperative or acute pain. When acute pain fails to subside and evolves into chronic pain, we are presented with a different challenge. Most commonly, chronic pain is treated with the use of opioids and other medications. While pharmaceuticals may be a good treatment option for some patients, others may experience undesirable side effects, or only negligible pain relief. Some patients may respond well to physical therapy modalities, nerve blocks, or other non-pharmacological treatments. If medications and other non-operative treatments fail to eliminate pain, surgical intervention may become necessary. Neurostimulation, both spinal and peripheral, has been advanced as an alternative treatment available for patients who suffer from chronic pain, and this article follows the progress of two patients with chronic foot pain.

CASE 1 A 43-year-old woman presented with right ankle pain after falling down several steps six years earlier. After failing an ankle arthroscopy and ankle distraction procedure with external fixation for treatment of her osteoarthritis, she underwent an ankle arthrodesis. One year after the ankle fusion, the patient underwent

Figure 1. Placement of the electrode on the tibial nerve.

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further surgery to remove painful hardware from the intramedullary nail and remove three plantar fibromas. Several months postoperatively, the patient was still experiencing increasing pain. On clinical exam, the patient had allodynia, burning pain along the sural and deep peroneal nerves, and a positive Tinelâ&#x20AC;&#x2122;s sign at both nerves. Subsequently, the patient found little relief from a sural and deep peroneal nerve decompression surgery, gabapentin, opioid pain medications, and physical therapy. She was then referred to a pain management physician, where sympathetic nerve blocks were administered, but they only offered several hours of relief. At this time, the patient was given a probable diagnosis of Complex Regional Pain Syndrome (CRPS 1) by the pain management physician.

After failing non-surgical treatment, the patient was offered the choice of a spinal cord stimulator (SCS) or peripheral nerve stimulation (PNS). After a discussion with the patient and a psychological evaluation to rule out any psychological sources of pain and evaluate the patientâ&#x20AC;&#x2122;s coping skills, the patient underwent a PNS placement on the common peroneal nerve.

CASE 2 A 40-year-old woman presented with a history of a motor vehicle accident, resulting in back and lower extremity pain, as well as cavus foot deformity. She underwent multiple foot surgeries after the accident to correct it, but continued to experience debilitating pain in the involved foot and lower extremity. On clinical exam, the patient demonstrated diffuse allodynia and pain with active and passive range of motion of the foot and ankle. After failing physical therapy, topical analgesics, injections, and pain medication to alleviate the pain, the patient wished to proceed with a PNS insertion. This patient also underwent a psychological evaluation, and proceeded to have a PNS implanted on both the tibial and common peroneal nerves (Figure 1).

IMPLANTABLE PERIPHERAL NERVE STIMULATION

RESULTS A questionnaire was developed to evaluate patient-rated subjective outcomes. Questions included pre-operative and post-operative pain levels, pain medication use, activities of daily living, and overall satisfaction of PNS implantation. A 1-10 visual analog pain scale was used to evaluate pain level. A chart review was also performed on the case study participants to gather other relevant health history information.

CASE 1: 43-YEAR-OLD FEMALE Prior to implantation of the nerve stimulator, the patient’s pain level was rated a 10/10 on the visual analog pain scale. The patient had pain with light touch, making it difficult to even put socks on.

After the PNS implantation, the patient’s pain was reduced to a tolerable level at 4/10, allowing her to return to normal activities of daily living, and greatly improving her sleeping pattern. This patient experienced a complication at four years post-implantation, with degeneration of the battery pack. She subsequently underwent surgical replacement of her original battery with a rechargeable version. At 12 years of follow-up, the patient’s pain level is still reduced to an average level of 2-3/10. The patient continues to use pain medication; however, she has decreased the amount, when compared to pre-implantation. Overall, she rated her level of satisfaction with the PNS as excellent.

CASE 2: 40-YEAR-OLD FEMALE: Prior to implantation of the nerve stimulator, the patient’s pain level varied from 8 to 10 on the visual analog scale. At four years of follow-up after the PNS implantation, the patient’s pain remained reduced to an average pain level of 3/10 (range 2-5).

The patient states that her pain is still present; however, she does have pain-free periods of one to six hours. The patient still utilizes gabapentin for her pain, but no longer requires narcotic pain medication. Overall, she rated her level of satisfaction with the PNS as excellent.

DISCUSSION Literature Review Although PNS has been used for treatment of pain for more than 50 years, very few large studies exist, and even fewer studies exist that focus on the lower extremity. The chronic pain etiologies documented and treated with PNS include pain secondary to entrapments, post-amputation pain, post-operative nerve pain, and direct nerve trauma (3,4). It should be recognized that due to the nature of PNS implantation, none of the above studies included a control group; therefore, pain relief due solely to placebo effect cannot be discounted.

Economics of Neurostimulation Even considering the high initial costs of neurostimulation due to device and implantation cost, it remains a viable treatment option due to its long-term cost effectiveness. In a cost-benefit analysis of neurostimulation for chronic pain, the authors retrospectively reviewed the records of 222 patients who received SCS or PNS. These patients achieved reductions in physician office visits, nerve blocks, imaging, emergency department visits, hospitalizations, physical therapy, and surgical procedures, resulting in a per-patient yearly cost savings of $30,221 (5). A literature review by Taylor, et al., found that the high cost of the SCS implant is offset by a reduction in post-implant health care savings, which can reach a break-even-point after 15 months to five years (6).

Potential Complications The authors of a study of peripheral nerve stimulation for treating chronic neuropathic pain reported that PNS does not carry the drawbacks of SCS and is a better alternative for nerve pain relief.

However, they also felt that PNS has significant shortcomings that lead to its limited use in pain relief (7). PNS implants can undergo possible migration, malfunction of electrodes over long distances, and require extensive tunneling of electrodes, which can lead to longer procedures and an increased risk of infection.

Nerve stimulators do come with risks and contraindications.

PNS cannot be used in patients with pacemakers or defibrillators, due to possible interactions between the two (8). Manufacturers state that patients should not be exposed to MRI, since it may cause dislodgement, damage to the device, or a “jolting” feeling (8). MRI with a PNS is not an absolute contraindication, but an MRI may cause the stimulator to turn off or alter its programming (9). Diathermy use, such as ultrasound, is also a contraindication, as it may cause tissue damage at the location of the implanted electrode (10). Adverse effects can include lead migration, lead breakage, infection, hardware malfunction, unwanted stimulation, and battery failure (10). Battery life and the need for a repeat surgery to replace batteries are also of concern. Newer rechargeable batteries on the market are beginning to address this concern.

Patient Selection As with any surgical treatment or implantation, a thorough evaluation of the patient with proper patient selection is paramount for a successful surgery. Novak and McKinnon state that patients should only be considered for PNS implantation when other surgical treatments fail (11). The authors listed three criteria that patients must meet before being considered appropriate for PNS implantation: pain should be localized to a specific nerve, pain should be relieved with an anesthetic block, and the patient should obtain satisfactory results on psychiatric evaluation (11).

Patients should undergo a psychiatric evaluation to uncover any underlying drug-seeking behavior, understand the psychiatric component to pain, and learn pain-coping skills.

Personal Experience The use of PNS at our institution has been reserved for patients with chronic neuropathic pain of the critical nerves below the knee. We only consider PNS for the common peroneal and tibial nerves. Additionally, the patient typically has pain for greater than six months and has failed treatment with various surgical interventions, medications, nerve blocks, and physical therapy.

We agree with Novak and McKinnon that pain symptoms should be isolated to the distribution of a specific nerve and should respond favorably to a diagnostic nerve block. The nerve block should relieve the majority of the patient’s symptoms, regardless of the duration of relief. In our experience, favorable response to a diagnostic nerve block obviates the need for a trial implantation. Many insurance companies, however, will not approve the use of PNS until a successful trial period (usually one week) is demonstrated. The fallacy of this argument is that it may take one to five months to achieve therapeutic neuromodulation, such that a one-week trial is not indicative of efficacy.

The medial surface of the tibial nerve has proved to be the ideal location for electrode placement. The undersurface of the nerve has more coverage for the lateral plantar nerve, while the posterior surface has more coverage for the calcaneal distribution.

Neuromodulation can be applied to the common peroneal nerve proper, or to either terminal branch, depending on symptoms.

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IMPLANTABLE PERIPHERAL NERVE STIMULATION

The deep or superficial peroneal nerves may be isolated for electrode placement, should symptoms be confined to their distribution.

We have discontinued the use of fascial grafts on the surface of the electrode. Although patients who received fascial grafts were able to tolerate neuromodulation sooner, they also lost effectiveness at the 12-14 month time period, requiring additional fine tuning.

Cost is a major obstacle. An average PNS with rechargeable battery costs $24,000, plus hospital costs; however, the longterm savings appear to be of value. The costs of medications, surgical interventions, physical therapy, and lost production in the workforce are staggering. The ability of our patients to return to a more normal and productive lifestyle represents a considerable post-implant health care savings to the system.

Some authors have cited breakage, migration, and extensive surgical procedures as obstacles to PNS implantation. At our institution, this is an approximately 45-minute procedure performed under general or spinal anesthesia on an outpatient basis.

CONCLUSION Numerous studies support the efficacy of SCS for pain relief; however, there is little research and published information with regard to the use and effectiveness of PNS. Slavin suggests there are several issues limiting the use of PNS in practice: the lack of awareness of PNS in the medical community, the lack of research related to PNS, and the lack of regulatory approval (12). There is a need for more evidence regarding PNS, especially in the lower extremity. The need also exists for a randomized, controlled study, which is difficult when an implantable device is needed. Information gathered from our case reports lends support for the use of neurostimulation for the treatment of chronic neuropathic lower extremity pain, though additional research is needed. ❏ Louis V. De Fazio, DPM, received his doctorate in podiatric medicine from Temple University School of Podiatric Medicine in 2014. He is a third-year resident and serves as the chief resident in Geisinger-CMC’s Podiatric Medicine and Surgery Residency. He is Board Qualified by the American Board of Foot and Ankle Surgery. Dr. De Fazio is a resident member of the American Podiatric Medical Association, the Pennsylvania Podiatric Medical Association, and the American College of Foot and Ankle Surgeons.

Felicia Bock, DPM, CWS, has been in private practice for the past five years in an office in Northeastern Pennsylvania focusing on diabetic foot care and foot deformities. She received her degree in podiatric medicine from Temple University and completed a Podiatric Foot and Ankle Surgery Residency at Geisinger Hospital in Scranton, Pennsylvania.

She is board certified in wound care by the American Board of Wound Management, board qualified by the American Board of Foot and Ankle Surgery, and is an active member of the American Podiatric Medical Association.

Guido A. LaPorta, DPM, MS, FACFAS, is the Director of Podiatric Medical Education at Geisinger-Community Medical Center, Scranton, Pennsylvania, and Our Lady of Lourdes Memorial Hospital, Binghamton, New York. He is a Clinical Professor of Surgery at the Geisinger Commonwealth School of Medicine, Temple University School of Podiatric Medicine and the New York College of Podiatric Medicine. He is currently President of the Pennsylvania Foot and Ankle Society.

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References 1. Johannes CB, Kim Le T, Zhou X, Johnston JA, Dworkin RH. The prevalence of chronic pain in United States adults: Results of an internet-based survey. J Pain. 2010;11:1230-1239.

2. Gaskin DJ, Richard P. The Economic Costs of Pain in the United States. J Pain.

2012;13(8):715-724.

3. Mobbs RJ, Nair S, Blum P. Peripheral Nerve Stimulation for treatment of chronic pain.

J Clin Neuro Sci. 2007;14: 216-221.

4. Rauck RL, Kapural L, Cohen SP, et al. Peripheral Nerve Stimulation for the Treatment of Postamputation Pain – A Case Report. Pain Practice. 2012;12(8):649-655.

5. Mekhail NA, Aeschbach A, Stanton-Hicks M. Cost Benefit Analysis of Neurostimulation for Chronic Pain. Clin J Pain. 2003;20(6):462-468.

6. Taylor RS, Taylor RJ, Van Buyten JP, Buchser E, North R, Bayliss S. The Cost Effectiveness of Spinal Cord Stimulation in the Treatment of Pain: A Systematic Review of the Literature.

J Pain Symptom Manage. 2004;27(4):370-378.

7. Deer TR, Levy RM, Rosenfeld EL. Prospective Clinical Study of a New Implantable Peripheral Nerve Stimulation Device to Treat Chronic Pain. Clin J Pain. 2010;26:359-372.

8. Boston Scientific Precision Plus Spinal Cord Stimulator System. Boston Scientific Website.

Available at: http://www.bostonscientific.com/en-US/products/spinal-cord-stimulator-systems/ precision_plus.html Accessed May 11, 2017.

9. Laryea JA, Schon LC, Belzberg AJ. Peripheral Nerve Stimulators for Pain Control.

Sem Neurosurgery.. 2001;12(1):125-130.

10. MedTronic. Important Safety Information for Neurostimulation Systems for Chronic Pain.

Available at: http://www.medtronic.com/us-en/patients/treatments-therapies/drug-pumpchronic-pain/important-safety-information/neurostimulators.html. Accessed May 11, 2017.

11. Novak CB, Mackinnon SE. Outcome following Implantation of a Peripheral Nerve Stimulator in Patients with Chronic Nerve Pain. Plast Reconstr Surg. 2000;105(6):1967-1972.

12. Slavin KV. Peripheral Nerve Stimulation for Neuropathic Pain. Neurotherapeutics. 2008; 5:100-106.

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Q&A: BIOPSYCHOSOCIAL RISK FACTORS FOR SPINAL CORD STIMULATION

Q&A: Biopsychosocial Risk Factors for Spinal Cord Stimulation

By Daniel Bruns, PsyD, and John Mark Disorbio, EdD

standard was that SCS was thought to be successful if pain reduction was ≥ 50% (9). Currently though, the scientific standards for assessing the effectiveness of spinal surgery are published in a consensus statement called the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). The IMMPACT study recommended that all scientific studies of spinal surgery used to reduce pain should assess five dimensions of medical treatment outcome: levels of pain, physical functioning, emotional functioning, patient satisfaction, and the presence of adverse symptoms (10).

Q: What is the prevalence of SCS complications?

A: One multicenter study of SCS reported that in 24% of cases SCS complications were severe enough that the stimulator needed to be removed, with an overall complication rate of 35% (11). In another study, SCS device complication rates rose to 45% after 24 months (12).

Q: Why are psychological evaluations required before SCS treatment?

A: Although SCS is an evidence-based treatment that is helpful for some patients, it is costly and associated with significant risks, and careful patient selection is indicated. In the case of invasive pain treatments, psychological factors can be stronger predictors of outcome than medical imaging (13).

This is important presurgically, as for example a severely depressed patient is unlikely to be happy with SCS outcome.

Consequently, the great majority of medical regulations, treatment guidelines, and payer policy statements require presurgical psychological evaluations prior to SCS treatments in order to predict a poor response to SCS treatment.

Q: When is spinal cord stimulation (SCS) treatment indicated?

Q: How do psychological tests predict the outcome of SCS?

A: SCS is most commonly used for pain that radiates into the extremities (e.g., chronic regional pain syndrome or radiculopathy) (1), and this treatment is supported by substantial evidence gained from clinical trials (2,3). Additionally, SCS has been used to treat spinal pain (4), ischemic pain such as angina (5), and movement disorders related to Parkinson’s disease (6).

A: SCS is a surgical treatment whose success is based on its ability to change the patient’s verbal behavior. Since pain is a subjective psychological experience (14), changes in the patient’s pain are based on changes in the patient’s report.

Thus, if as a result of SCS treatment a patient’s pain reports change from an 8 to a 3, the procedure is judged to be a success. Obviously though, numerous psychosocial risk factors could impact a patient’s subjective experience, or bias the patient’s report of pain.

Q: How do spinal cord stimulators reduce pain?

A: In the past, it was believed that SCS acted within the spinal cord to interfere with pain sensory signals in a way that replaced the perception of pain with a paresthesia or tingling sensation. More recent research suggests that the effect of SCS may extend beyond the spinal cord, as stimulation of the spinal cord has been shown to produce changes in the brain’s blood flow patterns and electrical activity (7).

Q: What constitutes a good outcome from SCS? A: It is actually problematic to define what constitutes a good outcome from pain-related surgery (8). For decades the

Q: What are the psychosocial risk factors for a poor SCS outcome?

A: A systematic review conducted by Celestin and colleagues determined that the psychosocial risk factors for which there was the strongest evidence for a poor outcome from SCS were these: pain intensity, poor pain coping, longer time with pain, poor physical functioning, somatic complaints, depression, anxiety, job dissatisfaction, older age, and lower level of education (15). The strength of this purely empirical approach is that it utilizes the variables for which there TH E PAIN PRACTITION ER

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Q&A: BIOPSYCHOSOCIAL RISK FACTORS FOR SPINAL CORD STIMULATION

is the strongest evidence. The weakness of this approach is that it ignores some variables that seem to be critically important. For example, chronic methamphetamine use is widely believed to be a risk factor for a poor SCS outcome.

However, it would be extraordinarily difficult to conduct a scientific trial of this, as it would require some of the SCS subjects to take a substance that is both dangerous and illegal. In general, due to the difficulties involved in studying the effects of severe psychopathology on surgical outcome, scientific studies are difficult if not impossible, and this leaves gaps in the literature.

To address the problem of the gaps in the literature regarding severe psychopathology and SCS outcome, we published a study that reviewed both the empirical literature and expert consensus statements (16). In addition to the risk factors identified by Celestin, this study also identified a strong expert consensus for other risk factors including substance abuse, dangerousness to self and others, trauma, personality disorder, and other variables that are difficult to study. In this study, we added these variables to the Celestin variables, and incorporated them into a biopsychosocial theoretical model called the Vortex Paradigm (a graphical representation of why some patients enter a “downward spiral” and fail to recover). These variables were empirically associated with dissatisfaction with care (subjective outcome) and unemployment (objective outcome) across multiple patient groups (spinal surgery, nonspinal surgery, acute injury, chronic pain, worker compensation, injury litigants, and brain injury) (16). This suggests that the Vortex variables are broadly associated with poor medical outcome.

Q: There are so many psychosocial risk factors. How do you draw a conclusion?

A: A poor response to SCS treatment can be predicted in a manner similar to the way we predict heart disease. That is, to predict heart disease we could develop a multivariate equation based on age, cholesterol, blood pressure, blood glucose, sedentary lifestyle, body mass index, genetics, and other variables. Patients high in all of these risk factors would be at elevated risk for heart disease. Similarly, the Vortex Paradigm would predict that a patient’s response to SCS treatment can be predicted by a multivariate equation that includes pain intensity, widespread pain, nonadaptive coping (e.g., catastrophizing or kinesiophobia), opioid dependence, conflicted patient-physician relationship, job dissatisfaction, depression, anxiety, childhood trauma, litigating for pain and suffering, etc. To draw a conclusion, you have to determine whether or not a patient’s cumulative level of risk is elevated.

Q: Are there guidelines for conducting these psychological evaluations?

A: Yes. There are well-established guidelines for performing psychological evaluations prior to SCS treatment, and for patients with chronic pain generally. Guidelines recommend that these evaluations should include reviewing the patient’s history, interviewing the patient about psychiatric risk factors, and administering standardized psychometric assessments (2,3). As noted above, the empirical and expert consensus literature for pre-stimulator psychological

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evaluations have been identified (16), and multiple guidelines have referenced the Vortex method (2,3). Additionally, psychological testing protocols for SCS presurgical psychological evaluations have been described in the clinical literature (17), and the relevant clinical and forensic standards for these assessments have also been reviewed (18).

Q: What tests were designed for this?

A: There are a number of psychological tests that can potentially be used to assess one or more Celestin/Vortex variables. For example, there are numerous psychometric measures of depression. However, given the number of variables to assess, the use of one multidimensional test is more efficient than administering a multitude of scales assessing one risk factor at a time. For example, three multidimensional standardized tests were developed to assess elevations of the Vortex variables. These tests are the BBHI 2 and BHI 2 (both developed for the assessment of pain and injury) (16,17) and the MBMD (19) (developed for the assessment of medical patients generally). The MBMD utilizes research on the Vortex variables, and lists in two tables whether each is elevated or not. The BHI 2 approaches this somewhat differently. The BHI 2 was developed in conjunction with the Vortex paradigm (16), and generates a composite Vortex score (the Rehabilitation Risk scale) with an overall percentile rank compared to other patients. Given the risks and costs associated with SCS, guidelines recommend a comprehensive assessment. However, as the Vortex variables seem to be broadly associated with poor medical outcome, the BBHI 2 test (which is much shorter than the other two) is also able to estimate the level of Vortex risk factors. The BHI 2 also generates a composite score based on the Celestin variables (the Presurgical Risk scale), which was constructed to predict the IMMPACT outcome variables. Both of these BHI 2 measures exhibited high reliability and very large effect sizes in tests of their ability to identify delayed recoverers (20).

Alternately, a test of psychopathology (MMPI-2-RF) (21) was used as part of a related system. Although the MMPI-2-RF does not directly assess pain or surgical risk, it can be used to assess several relevant variables using a method developed by Block and colleagues (22). The MBMD lists positive Block risk factors, and the BHI 2 Rehabilitation Risk score correlated .79 with Block’s system (20).

Q: Should there be any psychometric differences in what you measure in psychological evaluations for variations of SCS (e.g., spinal cord vs. nerve root vs. peripheral nerve stimulation)?

A: No. We know of no empirical or theoretical studies suggesting that any of the variants of SCS have unique psychosocial predictors of outcome. To the contrary, as noted above, it appears that the Vortex risk factors appear to be broadly predictive of both SCS outcome and a poor outcome from medical treatments generally (16).

In contrast, there is research suggesting that regarding medical outcome from lumbar surgery, psychosocial predictors of whether or not a patient will report decreased pain are somewhat different from psychological predictors for im-

Q&A: BIOPSYCHOSOCIAL RISK FACTORS FOR SPINAL CORD STIMULATION

provement in function (23), and the psychological predictors of rehabilitation outcome are different than the predictors of opioid craving (20). Thus the only differences in psychosocial predictors that have been reliably demonstrated are associated with what predicts a particular type of outcome, but not surgery type.

Q: When do you exclude the patient from treatment?

A: Virtually every patient with chronic pain has some risk factors. The more important consideration is the cumulative level of risk. As psychometric signs of a poor outcome increase from high to extremely high there should be increasing caution about surgery and increasing consideration of conservative alternatives. Note that some risk factors such as depression may respond readily to treatment.

Q: Do these tests have race or gender biases?

A: In general, standardized tests are developed with the intent of eliminating biases. One study specifically tested the BHI 2 Presurgical and Rehabilitation Risk scores and found no indication of race or gender bias (20).

Q: What are the most common misperceptions about psychological evaluations for SCS? A: The most common misperceptions are that these evaluations are intended to be used by physicians to identify “crazy” patients whom they do not want to treat, or to be used by payers to dismiss a patient’s pain as being “in your head” so that they can deny coverage. These are not the intended purpose. The purpose for which these evaluations are intended is to predict the IMMPACT variables: As a result of this treatment, will a particular patient report less pain, less distress, improved function, and satisfaction with care? If a patient is at risk for a poor outcome, can those risks be reduced? To the extent that psychosocial risk factors can be ameliorated by behavioral treatments prior to SCS, SCS outcome would be expected to improve. In those cases where patients are not thought to be good candidates for SCS, suggestions should be made regarding what treatments could be offered to the patient, such as behavioral methods of pain management. ❏ For additional information, including webinars and a pictorial glossary of SCS-related terms, go to www.heathpsych.com/scs.html Daniel Bruns, PsyD, has coauthored both research and applied articles on the evaluation of SCS candidates, served on eight medical guideline task forces for chronic pain, and as a technical expert for CMS. He is a coauthor of the BHI-2 and BBHI-2 biopsychosocial assessment measures.

John Mark Disorbio, EdD, has coauthored both research and applied articles on the evaluation of SCS candidates, served on the National Pain Foundation board for six years, and served as a consultant for two SCS manufacturers. He is also a coauthor of the BHI-2 and BBHI-2 biopsychosocial assessment measures.

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2. American College of Occupational and Environmental Medicine. Chronic pain treatment guidelines. 3rd ed. Westminster, CO: Reed Group; 2017.

3. Colorado Division of Workers’ Compensation. Rule 17, Exhibit 9: Chronic Pain Disorder Medical Treatment Guidelines. 2012; http://www.healthpsych.com/tools/chronicpain.pdf. Accessed April 4, 2017.

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Pain Physician. 2016;19(1):E33-54.

5. Pan X, Bao H, Si Y, et al. Spinal cord stimulation for refractory angina pectoris: a systematic review and meta-analysis. Clin J Pain. 2016.

6. de Andrade EM, Ghilardi MG, Cury RG, et al. Spinal cord stimulation for Parkinson’s disease: a systematic review. Neurosurg Rev. 2016;39(1):2735; discussion 35.

7. Bentley LD, Duarte RV, Furlong PL, Ashford RL, Raphael JH. Brain activity modifications following spinal cord stimulation for chronic neuropathic pain: A systematic review. Eur J Pain. 2016;20(4):499-511.

8. Carragee EJ, Cheng I. Minimum acceptable outcomes after lumbar spinal fusion. Spine J. 2010;10(4):313-320.

9. Turner JA, Loeser JD, Bell KG. Spinal cord stimulation for chronic low back pain: a systematic literature synthesis. Neurosurg. 1995;37(6):10881095; discussion 1095-1086.

10. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1-2):9-19.

11. Hayek SM, Veizi E, Hanes M. Treatment-limiting complications of percutaneous spinal cord stimulator implants: a review of eight years of experience from an academic center database. Neuromodulation.

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12. Kumar K, Taylor RS, Jacques L, et al. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurg. 2008;63(4):762-770; discussion 770.

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14. Merskey H, Bogduk N. Classification of chronic pain. 2nd ed. Seattle: IASP Press; 1994.

15. Celestin J, Edwards RR, Jamison RN. Pretreatment psychosocial variables as predictors of outcomes following lumbar surgery and spinal cord stimulation: a systematic review and literature synthesis. Pain Med. 2009;10(4):639-653.

16. Bruns D, Disorbio JM. Assessment of biopsychosocial risk factors for medical treatment: a collaborative approach. J Clin Psychol Med Settings.

2009;16(2):127-147.

17. Bruns D, Disorbio JM. The Psychological Assessment of Patients with Chronic Pain. In: Deer TR, ed. Comprehensive Treatment of Chronic Pain: Medical, Interventional, and Behavioral Approaches. New York: Springer; 2013:805-826.

18. Bruns D. Clinical and forensic standards for the psychological assessment of patients with chronic pain. Psychol Inj Law. 2014;7(4):297-316.

19. Millon T, Antoni M, Millon C, Minor S, Grossman S. Millon Behavioral Medicine Diagnostic manual supplement: Pain patient reports. Minnealpolis: Pearson Assessments; 2010.

20. Bruns D, Disorbio JM. BHI 2 Medical Intervention Risk (MIR) Report Manual. Minneapolis: Pearson; 2016.

21. Ben-Porath YS, Tellegen A. MMPI-2-RF™ Manual. Minneapolis: University of Minnesota; 2008.

22. Block AR, Gatchel RJ, Deardorff WW, Guyer RD. The psychology of spine surgery. Washington DC: American Psychological Association; 2003.

23. den Boer JJ, Oostendorp RA, Beems T, Munneke M, Evers AW. Continued disability and pain after lumbar disc surgery: the role of cognitive-behavioral factors. Pain. 2006;123(1-2):45-52.

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