Women on the Verge: Sleep, Sex, and Pain at Midlife

Women on the Verge

Sleep, Sex, and Pain At Midlife Hal Blatman, MD, DAAPM, ABIHM www.blatmanpainclinic.com

Disclosure Information • Speakers Bureau: Standard Process

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Learning Objectives • Describe how stress affects pain • List herbal therapies that help improve resiliency to stress • Describe how to apply relaxation options for reducing the cumulative effect of stress • Describe how bio-identical hormone therapies can improve quality of life 3

Our Patient

(Ourselves)

• 45 yr old woman • Mother, husband, daughter • 2 children, jr high, one with asthma

–Band, basketball, soccer, church • Husband with full time job, travels some • Mother with fibromyalgia, 90 min away • Full time job, customer service 4 • SuperMom

Our Patient-Symptoms • Headache • Fatigue • Insomnia • Neck and shoulder pain • Anxiety • Mild weight gain 5

How Does Stress Affect Pain?

• Makes it worse • Makes perception of pain worse • Decreases efficacy of coping mechanisms

–Associated with depression and anxiety • Wears out body energy reserves

–Pain patient => more sensitive to physical activity –Increases fatigue (adrenal)

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Stress Worsens Myofascial Pain • Myofascial pain comes from trigger points in muscle and fascia • Myofascial pain is local and referred • Myofascial trigger points interact with autonomic nervous system • Autonomic nervous system is part of stress mediation 7

Sympathetic Nervous System and Myofascial Pain • Work done by Hubbard/Gevirtz • Needle transducer in shoulder trapezius muscle

–One in trigger point, one not • Relationship with stress

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Myofascial Trigger Points Show Spontaneous Needle EMG Activity (Hubbard & Berkoff, 1993)

Trigger Point vs. Adjacent nEMGs across Conditions) McNulty,W., Gevirtz,R.N., Hubbard, D., and Berkoff,G. (1994) Needle electromyographic evaluation of trigger point response to a psychological stressor. Psychophysiology,31, (3), 313316.

Counting Forwards

Backwards

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Headphones for Relaxation tape

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Cough affects both electrodes More effect in trigger point

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Cough has persistent effect

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Then relaxation...

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Then STRESS...

Counting backwards by 7

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Progressive STRESS....

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Progressive STRESS....

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Progressive STRESS....

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Myofascial Pain and Stress –MTrPs transmit pain through sympathetic nervous system afferent fibers –MPS is sympathetically mediated autonomic nervous system pain –Numbness, Tingling, Burning, Cramping, Aching PAIN –When SNS upregulates, pain increases 26

As We Get MORE STRESSED • Sympathetic nervous system effects increase • Trigger point activity increases • Orchestra of pain generators plays louder...all over the body

–Muscle tension, headache, back pain.....

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Up-regulation of SNS Due to STRESS Causes Insomnia and Pain

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We were designed to run away from tigers.

How Many Tigers Do We See In One Day??

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Many More Than We Designed to See • Every time the phone rings • Every time a traffic light changes • Every time a horn beeps • Every time a door slams • Every time we hear a raised voice • Every time we watch the news on TV 31

Early to Mid-life Women Stress..

• Job, career • Children

–Carpool, sports, school, clothes, food • Laundry • Homework • Aging parents • Husband?

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What Happens When we see a TIGER? • Walter Cannon, Harvard physiologist, 1930’s coined term: ‘fight or flight’ –Innate defense mechanism that activates in face of threat or danger –Recruit resources to fight to death or flee tiger for life

• Cortisol release, liver releases stored sugar, --> increased cerebral-cardiacpulmonary-large muscle blood flow 33

Historical Context • Cannon’s work was then extended by Hans Selye (1907-1982)

• Studied influence of stress on person’s ability to cope with and adapt to injury and disease • Realized that a variety of ailments manifested similar symptoms 34

Goldstein DS, Kopin IL. Stress 2007; 10(2): 109-120

Historical Context • Observed that the same characteristics & constellation of physiological responses occurred in rats subjected to a variety of intense stimuli –These included adrenal enlargement, thymus & spleen atrophy & GI ulcers

• Termed the series of responses the General Adaption Syndrome (GAS) 35

Stress • Hans Selye, 1950’s, “The Stress of Life”

–Natural response to stress was same, tiger or test with time limit • Boss with a scowl • Argument with spouse

–3-Phase General Adaptation Syndrome • Alarm • Resistance • Exhaustion 36

Diagram of GAS

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General Adaptation

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Adrenal Fatigue

• Laboratory Testing • Saliva

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The Coping Process • Coping with stress is a continual, dynamic, interactional process • Involving what a person thinks & does in dealing with the demand/s (real or perceived) • Involves 3 stages: – Primary appraisal, where it is decided whether the stress is of concern – Secondary appraisal, where personal resources are assessed, how much control do I have?, memories, knowledge etc 40

The Coping Process • The 3rd stage is coping, taking whatever actions are deemed appropriate • May involve action and/or cognitive adjustment (self-talk)

Schafer W. Stress Management for Wellness, 4th Ed, Thomson Wadsworth, Belmont CA, 2000, pp. 292-318 41

Coping Skills • Knowledge

–Knowledge of the way things are empowers –Stress arises from incomplete knowledge or information

• Inner resources

–Beliefs that invoke mental mechanisms that alter inner or outer reality to minimize stress –Perception is reality Ray O. Am Psychol 2004; 59(1): 29-40

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Coping Skills • Social support

–The interpersonal relationships that sustain us • Spirituality

–A purpose in life

Ray O. Am Psychol 2004; 59(1): 29-40 43

Allostatic Load • Term coined by McEwen and Stellar-1993 • Physiologic consequences of chronic exposure to repeated stress • Neural and endocrine response

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Glucocorticoids • Much of the allostatic load caused by ongoing stress is due to GCs • GCs are the end product of the HPA axis • They impact every organ system & physiologic, cellular & molecular network • Too much or too little of the HPA axis and/or GC activity will be problematic Chrousos GP, Kino T. Stress 2007; 10(2): 213-219

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States Associated With Hyper/Hypo Activation of HPA Axis Increased Activity •

Anorexia nervosa

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Hyperthyroidism

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Acute illness

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Obsessive compulsive disorder

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Panic disorder

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Excessive exercise

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Depression including SAD

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PTSD

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CFS

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Fibromyalgia

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Hypothroidism

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Menopause

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RA

Decreased Activity

Juruena MF, Cleare AJ. Rev Bras Psiquiatr 2007; 29(1): 19-26

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Adaptogens • Nicholai Lazarev, Soviet scientist pioneer in toxicology and preventive medicine

–1930s discovered chemicals, even small dose, cause similar alarm rxns –If prolonged, body will adapt by altering physiological response

• Adaptation gradually disturbs homeostasis, damaging to health 47

Adaptogens • Nicholai Lazarev

–Began looking for substances that could improve resistance to toxins, and also correct general adaptation reaction to all kinds of stressors –defined adaptogen in 1947 • Substance that elicits state of raised resistance to stressors

• Supplement ability to deal with anxiety, fatigue, trauma 48

Adaptogens • Brekhman chose stamina as index of vitality

–April 1948, 100 soldiers run 3 k race –½ given ginseng; ½ given placebo • Ginseng group finished ave. 53 seconds faster

• Ginseng drawbacks

–Poor availability –High cost –Effectiveness varied • Men responded > women, elderly>young

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Eleutherococcus • Brekhman looked for herbs able to survive in harsh environments

–Eleutherococcus (Siberian Ginseng) • Clinical studies demonstrated improved stamina and recovery, increased O2 intake, improved performance • 50% less damage to immunity with anti-CA drugs – 50% decreased drug dose 50

Adaptogen -Functional Definition Brekhman & Dardymov 3 traits of adaptogens:

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Non-specific activity (hence act on GAS) - No particular target organ or system •Help create balance and normalization

•Non-toxic & do not influence the body more than required Brekhman II, Dardymov IV. New substances of plant origin which increase non specific resistance. Ann Rev Pharmacol. 1969; 9: 419-30 51

Key Herbal Actions • Adaptogens conserve adaptation energy

– Eleuthero – Ashwaganda – Rhodiola • Tonics increase or release adaptation energy

– Korean Ginseng • Adrenal tonics support and restore the adrenal cortex

– Licorice – Rehmannia

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Herbal Medicines Therapeutic Strategy • Support the immune system

–Echinacea –Astragalus • Minimize effects of stress on nervous system with nervine tonics

–St John’s Wort –Skullcap 53

Licorice • Glycyrrhiza glabra root is well known for a wide range of therapeutic activities & indications in several traditional medicine systems Text • It contains triterpenoid saponins, especially glycyrrhizin (GL), as well as flavonoids • Actions:

– Adrenal tonic – Anti-inflammatory – Demulcent, expectorant, antitussive

Latin verb demulcere: to caress. Forms a soothing film over mucous membrane.

Bone K. The Ultimate Herbal Compendium, Phytotherapy Press, Warwick, 2007, pp. 47

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Licorice • Both the BHP & BHC describe Licorice as an adrenal agent & adrenocorticotropic (herbalists now regard as adrenal tonic)1,2

• Indicated for primary adrenocortical insufficiency & autoimmune Addison's disease1,2 • The adrenocorticotropic activity is an important action to note as the research that follows can lead to confusion, i.e. that Licorice preserves cortisol with the possible contraindication for elevated cortisol states 1. British Herbal Pharmacopoeia. BHMA, Bournemouth, 1983, pp. 104-105 2. British Herbal Compendium. BHMA, Bournemouth, 1992, pp. 145-148

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Licorice • It neither stimulates nor inhibits the production of cortisol, but rather preserves, protects & restores the cortisol producing machinery • Where there is cortisol excess the glands are being overtaxed & where there is cortisol deficiency they are depleted • Either way there is the need for adrenal support 56

Licorice • In the 1950s Licorice extract was found to be a successful medical treatment for some cases of Addison's disease • Patients could be maintained on 3–60 g/day of extract, the lower dosage was used when the disease was controlled Knowles JP. Proc R Soc Med 1958; 51: 178 57

Licorice • There may be an increased sensitivity & cummulative action from Licorice • Suggestion that Licorice may assist in the 1 recuperation of the adrenal cortex

1. Mills SY. The Essential Book of Herbal Medicine. Penguin Arkana (Penguin), London, 1991, pp. 505-510 58

Licorice Dose In a clinical study, oral administration of GL (150–300 mg/day) blocked the effect of the glucocorticoid dexamethasone in lowering the amount of urinary metabolites of cortisol as the result of pituitary (ACTH) inhibition

Glycyrrhiza glabra

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Licorice Dose • Licorice root 7:1 extract

–250 mg from Glycymhiza glabra root 1.75g • Dose 1-2 tablets 2-3x/day

–Often times herbs are not used in high enough dose

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Licorice Indications: • Adrenal depletion, to aid the recovery of the adrenal cortex • To support adrenal cortex function in times of high stress • Fatigue, anxiety, sleeplessness or reduced immune function during periods of prolonged stress • Chronic illness 61 • Chronic autoimmune diseases

Licorice and Central Obesity • Licorice is well documented to inhibit the activity of 11 beta-HSD type 2. This is responsible for its aldosterone-like side effects • A group of Italian scientists found that Licorice for 2 months reduced body fat mass in 15 healthy volunteers without any change in calorie intake • BMI did not change Armanini D et al. J Endocrinal Invest 2003; 26(7): 646-650

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Licorice Cautions & Contraindications: • Contraindicated in hypertension & edema dependent on dose & duration of use • Caution is advised in patients taking cortisol or prednisolone, & in the elderly & those with cardiac, renal or hepatic disease • Do not prescribe if patient is taking potassium-depleting diuretics • Patients who are prescribed Licorice preparations high in GL for prolonged periods should be placed on a high potassium & low sodium diet and closely monitored for blood pressure increases & weight gain 63

Rehmannia • In traditional Chinese medicine (TCM) Rehmannia glutinosa unprocessed root is used to:

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reduce heat in the blood to nourish yin & promote the production of body fluid

• Indications for this type of Rehmannia include: -

febrile diseases skin eruptions nosebleed

Pharmacopoeia of the People’s Republic of China, English Edn. Beijing: Chemical Industry Press, 1997

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Rehmannia • In western herbal medicine, Rehmannia is regarded as an adrenal tonic, due mainly to the activity demonstrated in experimental studies • Main active ingredients:

–Monoterpenes with glucose • >12 iridoid glycosides – 3-11% catalpol

• Stimulate production adrenal cortical hormones 65

Rehmannia • Rehmannia may work by inhibiting the negative feedback from the glucocorticoid to the pituitary gland • These results also suggest that Rehmannia supports the cells of the adrenal cortex & pituitary during times of prolonged stress Chen JK, Chen TT, Crampton L. Chinese Medical Herbology and Pharmacology. Art 66 of Medicine Press, California, 2004

Rehmannia • Rehmannia treatment prevented or reversed morphological changes in the pituitary & adrenal cortex • Appearing to antagonize the suppressive effect of glucocorticoids on the hypothalamic-pituitary-adrenal axis Cha LL et al. Chin J Integr Trad West Med 1988; 8(2): 95-97 67

Rehmannia Rehmannia glutinosa Rehmannia rhizome 5:1 extract yields 150 mg from rhizome 750 mg Dose: 1 tablet 2 -3 times per day 68

Rhodiola • Prevent stress-induced catecholamine activity in cardiac tissue1 • Reduce adrenaline-induced arrhythmias in animals2

1. Maslova LV et al 1993 2. Lishmanov, et al 1987.

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Vitamins • Vitamin C • Thiamine • B6 • Lipoic Acid • Tyrosine

–Precursor to catecholamines –Alleviates stress induced depletion 70

Stress Control Recommendations • Energy Tonic

–Rhodiola, Korean Ginseng • To prevent adrenal depletion • For the patient who is heading in that direction • Good support for those with busy lives & who are under constant stress • Will improve both physical & cognitive performance to enable a person to get on top of things 71

Stress Control Recommendations • Long Term Immune Support

–Astragalus, Echinacea, Eleuthero • For those where constant stress has resulted in immune suppression in all its manifestations • For the chronic phases, not acute, in which case Short Term Immune Support is used along the remedies that treat the system involved e.g. Short Term Lower Respiratory Support for Bronchitis, Urinary Tract Support for UTIs etc.

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Protocols • Patients most often are impacted by psychological symptoms that are an expression of the state of the NS • These symptoms relate to which arm of the ANS is dominating at that time • When the Yin hormones such as epinephrine are dominating, the thoughts of future events will produce anxiety • When the Yang hormones such as GCs are dominating, the thoughts of past events will73 produce depression

Stress and The Brain • Recent stress research discusses adverse effects on various brain regions especially the hippocampus • Upon exposure to stressors, GCs are released & act on target cells including brain cells • This central action of GCs is associated with behavioral, neurochemical & neurodegenerative changes • GC neurodegenerative changes of the hippocampus, involved in memory processes & other cognitive functions as well as in the regulation of the HPA axis 74

STRESS (mind) Perpetuates Pain • L-theanine 50-200 mg

– Amino acid has been shown to promote the generation of alphabrain waves, an index of relaxation. It may also boost natural resistance to microbial infections.

• Herbs – only half a TIGER

– Passion flower – Valerian root – Hops – Lemon balm – Jujube seed – Magnolia – Rhodiola

Additional Help for Stress • Herbal therapies that help improve resiliency to stress • Biofeedback and meditation • Massage • Acupuncture • Yoga • Social structure to help with coping 76 • Etc..

Heart Rate Variability (testing and biofeedback)

• Low HRV is associated with depression and anxiety • Low HRV associated with insulin resistance-CHF, diabetes, hypertension, wgt gain • Low HRV associated with hormonal imbalance (DHEA, cortisol) 77 • Low HRV associated with chronic stress

Heart Rate Variability (testing and biofeedback)

• Training is associated with increased DHEA-s and decreased salivary cortisol • Decreased indicators of stress

–Anxiety –Fatigue –Positive outlook • May reduce cumulative effect of stress Pipe et al Stress Health, 2011 78

Woman on the Verge..

• Tired • Insulin resistant • Stressed • Neck and shoulder discomfort • Headaches • Loss of libido • Still holding together thanks to soda, coffee, 79 energy drinks, and fast food

Interactions between glucocorticoids and sex hormones in regulation of metabolic syndrome

• Metabolic syndrome is related to increased inflammation and immune response, balanced by increase in glucocorticoids • Glucocorticoids

– Induce insulin resistance – Alter lipid metabolism – Favor fat deposition – Decrease androgen synthesis

Green lines: increasing or enhancing effects; red lines decreasing or inhibiting effects; black lines: direct relationships, consequences

Interactions between glucocorticoids and sex hormones in regulation of metabolic syndrome

• Estrogens

– Decrease inflammation – Reduce glucocorticoid response • Low estrogens allow manifestation of metabolic syndrome

Green lines: increasing or enhancing effects; Red lines decreasing or inhibiting effects; Black lines: direct relationships, consequences

Alemany M, Front Endocrinol 2012;3:27. Epub 2012 Feb 27.

Low Hormones-Symptoms • • • •

Insomnia Anxiety Depression Fatigue

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Night sweats Mood swings Low libido Vaginal dryness 82

Use of Bio-Identical Hormones • Blood and saliva testing • Balance progesterone, estrogens, and testosterone • Progesterone is calming • Low libido consider testosterone • Administration

– Transdermal – Transmucosal (buccal/vaginal) – Pellet

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Summary • Stress increases pain • Herbal therapies can help improve resiliency to stress • Relaxation options for reducing the cumulative effect of stress • Bio-identical hormone therapies can improve quality of life 84

Thank You 85