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Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Fibromyalgia and Global Pain Syndromes:
A Functional and Integrative Approach
• Naturopathic Doctor (ND)Licensed in CT and VT
• Doctor of Chiropractic (DC)
• Certified Clinical Nutritionist (CCN)
• Diplomate of the American Clinical Board of Nutrition (DACBN)
• Institute for Functional Medicine Certified Practitioner (IFMCP)
• Vice Provost, Health Sciences Director, Human Nutrition InstituteAssociate Professor of Clinical SciencesUniversity of Bridgeport, Conn.
• Chief Medical Officer,‐Designs for Health, Inc.‐Diagnostic Solutions Laboratory, LLC
• Private Practice (Fairfield, CT) Whole Body Medicine
Dr. David M. Brady
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• Chief Medical Officer: Designs for Health, Inc. (DFH)
• Chief Medical Officer: Diagnostic Solutions Labs (DSL)
• Consultant: Cell Science Systems, Inc. (CSS‐ALCAT)
Disclosures
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• “Fibrositis” (Sir William Gowers, 1904)
• “Psychogenic rheumatism” (circa 1950)
• “Fibromyalgia” (Current)
• “Central allodynia” (Proposed)
Fibromyalgia Evolution
Age Distribution of Fibromyalgia by Gender
Source: Mense S, Simons DG. Muscle Pain. Lippincott, William, & Wilkins; 2001.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
FMS literature started soaring in the mid to late 80’s
Source: Mense S, Simons DG. Muscle Pain. Lippincott, William, & Wilkins; 2001.
ICD-9
1990 ACR Criteria for Diagnosis of FMS
1. History of Widespread Pain – defined as:
a) Pain on both sides of body
b) Pain above and below the waist
c) Axial skeletal pain is present
2. 11 of 18 Tender Points – defined as < 4 kg pressure:
a) Occiput
b) Lower cervicals (ant‐lat’l)
c) Trapezius
d) Supraspinatus
e) Second Rib (anterior)
f) Lat’l Epicondyle
g) Gluteal muscles
h) Greater Trochanter
i) Medial Knee
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Mense S, Simons DG. Muscle Pain. Lippincott, Williams & Wilkins; 2001.
• Arbitrary locations
• Determined by consensus, not anatomy
The Original 18 Tender Point Locations
Pressure Algometer to Verify Tender Points < 4 kg
Source: Mense S, Simons DG. Muscle Pain. Lippincott, William, & Wilkins; 2001.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
– Females generally have lower APT values than males
– If < 4 kg is set as “abnormal,” then statistics are skewed
– May this partially explain the 20:1 female‐to‐male ratio?
– May need 2 sets of APT criteria, one for each gender?
• Fibromyalgia is a painful, non‐articular condition…; it is the commonest cause of chronic, widespread musculoskeletal pain. It is typically associated with persistent fatigue, non‐refreshing sleep and generalized stiffness. Women are affected 10–20 times more than men.
• Fibromyalgia is often part of a wider syndrome encompassing: headaches, irritable bowel syndrome, irritable bladder, dysmenorrhea, cold sensitivity, Raynaud’s phenomenon, restless legs, atypical patterns of numbness and tingling, exercise intolerance and complaints of weakness.
• A varying proportion of fibromyalgia patients experience significant depression or anxiety which may contribute to the severity of symptoms or result from having chronic pain.
• Typically symptoms are worse during periods of cold or damp weather, at the beginning/end of the day and during periods of emotional stress.
1992 World Congress on Myofascial Pain and Fibromyalgia Syndrome convenes and publishes the Copenhagen Declaration:
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Central Sensitivity Syndrome
Sarzi‐Puttini P et al. Chronic widespread pain: from peripheral to central evolution. Best Pract Res Clin Rhematol, 2011 Apr;25(2):133‐9
• Not overtly or systemically inflammatory
• Not autoimmune (as far as we can tell)
• Not a muscle disorder
• Not the same as Chronic Fatigue Syndrome (CFS)
Dispelling Some FM Myths
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• Viral: EBV, CMV, HSV, HIV, Hep. C, Coxsackie, parvovirus, etc.• **Neurotransmitters:
– Serotonin and norepinephrine deficiency– Substance P excess – Alterations in nocturnal melatonin
• Hormones: Thyroid, adrenal, growth hormone• Sleep disorders• Psychological: Inability to cope with stressors
(post‐traumatic stress disorder, PTSD)• Neurological: Increased sympathetic drive to muscles, cervical compression• Nutritional: Mg, malic acid, B vitamins, Mn, Se• Metabolic:
– Mitochondrial dysfunction– Cumulative toxic load– Intestinal dysbiosis/”leaky gut”– Heavy metals (i.e., aluminum/mercury)
Proposed FMS Etiologies Through the Years *
*Many unsubstantiated by any significant evidence‐base*Fitzcharles MA et al. Fibromyalgia: evolving concepts over 2 decades, CMAJ, Sept. 17, 2013, 185(13)** Arnold LM. Biology & Therapies in Fibromyalgia, Arthr Res Ther, 2006; 8(212)
• History! – Subjective global tenderness/pain, assoc. S/Sx
• Examination– Objective global tenderness/pain
• Labs– Rule out other disease/disorder
FMS Diagnosis per ACR Criteria
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
No Fibromyalgia Factor Test!
• Chronic fatigue syndrome (CFS)• Myofascial pain syndrome (MPS)• Organic depression/anxiety• Multiple bursitis/tendonitis sites• Connective tissue disorders (SLE, RA, polymyalgia rheumatica, mixed
connective tissue disease) • Stealth infections: Lyme and co‐infections, viral• Endocrine myopathies (hypothyroid, adrenal, growth hormone)• Dysglycemia (insulin resistance/syndrome X)• Anemia• Multiple sclerosis• Occult malignancy• GI dysbiosis and toxicity• Etc.
FMS Differential Diagnosis
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
FM Pain Diagram
FMS and /or Somatization Disorder
Regional MyofascialPain Syndrome
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Tender Points for Diagnosis of Fibromyalgia
Say Goodbye To Tender Points?
Wilke WS. New developments in the diagnosis of fibromyalgia syndrome: Say goodbye to tender points? Cleveland Clinic Journal of Medicine, Vol 6, No 6, June 2009
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Drug Therapy:• Tricyclics (amitriptyline, clomipramine, dothiepin, etc.) • SSRIs (fluoxetine, citalopram, etc.)• MAOIs (moclobemide)• SSNRIs (duloxetine, venlafaxine, milnacipran, etc.)• Alpha‐2 delta ligands /Gabapentinoids (pregabalin, gabapentin)• GABA receptor agonists (Sodium oxybate /SXB)• Low Dose Naltrexone (LDN)• 5‐HT3 antagonists (ondansetron, tropisetron, etc.)• NMDA antagonists (tramadol, dextromethorphan, etc.)• Dopamine 3 agonists (pramipexole, etc.)• Cyclobenzaprine • NSAIDS• Acetaminophen • Lithium carbonate
FM Medical Management Over The Years
Arnold LM. Biology and therapy of fibromyalgia: new therapies in fibromyalgia. Arthritis Res Ther. 2006; 8:212.
(Current trends in therapy)
“Recent pharmacological treatment studies have focused on selective serotonin and norepinephrine reuptake inhibitors (SSNRIs), which enhance serotonin and norepinephrine neurotransmission in the descending pain pathways and lack many of the adverse side effects associated with tricyclic medications.”
Arnold LM. Biology and therapy of fibromyalgia: new therapies in fibromyalgia. Arthritis Res Ther. 2006; 8:212.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Loggia M et al. Evidence for brain glial activation in chronic pain. Brain, 2015, Jan 12.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
All can be associated with fatigue and muscle tenderness
Schneider M, Brady D, Perle S. J Manipulative Physiol Ther. 2006;29:493‐501.
Fibromyalgia Syndrome Clinical Reasoning Guide
“Classic” FMS‐ Sleep disorder
‐ Anxiety
‐ Depression
‐ Alterations of CNS chemistry
‐ Neuro‐endocrine imbalances
Organic‐ Anemia‐ Lyme disease‐ Hypothyroidism‐ Inflammatory arthritides
‐ Dysglycemia‐ Occult carcinoma‐ Multiple sclerosis
Functional‐Mitochodrialdysfunction
‐ Toxicity‐ GI dysbiosis‐ Nutritionaldeficiencies
Musculoskeletal‐ Multiple TrPs‐ Joint dysfunction‐ Muscle imbalance‐ Postural distortion‐ Undiagnosed disc/facet lesions
“Pseudo ‐ FMS”The various disorders
that are misdiagnosed as FMS
1) Organic diseases
2) Functional disorders
3) Musculoskeletal disorders
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• Biopsy studies = No tissue specificity in FMS patients
• EMG studies = No specific changes in muscle tone
• Drug studies = No benefit of NSAIDs or steroids over placebo; but significant benefit of SSRI/SSNRIs
• Pain Studies = FMS patients feel “pain” at tender points at decreased thresholds when compared to “control” points.
All Over Their Bodies…
CONCLUSION = No peripheral soft tissue is the pain generator in FMS
What Exactly Are These Tender Areas/Points?
Borg‐Stein J, Stein J. Trigger points and tender points: one and the same? Rheum Dis Clin North Am. 1996 May;22(2):305‐22.
Arnold LM. Biology and therapy of fibromyalgia: new therapies in fibromyalgia. Arthritis Res Ther. 2006; 8:212.
If No Soft Tissue is the Pain Generator in FMS, From Where is the Pain Coming?
Most likely the CNS!
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
The Muscle Pain Pathway: Spinothalamic Tract
The Muscle Pain Pathway: Spinothalamic Tract
NorepinephrineTricyclicsSSNRI
*Seems to havebenefit for limitedamount of time in about 25% of subjects
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
The Muscle Pain Pathway: Spinothalamic Tract
Alpha-2 delta ligandsGabapentinoids
*Burning Pain*Makes Sleepy
• The spinal cord can be viewed as a “peripheral brain”; it contains both grey and white matter.
• Interneurons within the dorsal horn integrate and modify all incoming sensory input.
• Grey matter of the spinal cord is capable of associative conditioning or “learning.”
• Complexity of the cord’s interneuronal connections allow for the phenomenon of referred pain to occur.
The Spinal Cord
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Simplified Convergence‐Projection Theory of Referred Pain
Spread of Pain to Normal Tissues by Spillover of Substance P
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Descending Antinociceptive System
Dysfunction of the DANS is now Thought to be the Major Cause of Classic FMS by the Major Researchers in the Field
Julien N, et al. Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain. 2005;114:295‐302.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Picture of Pain
A) Sensory Cortex
Discrete Pain Localization
B) Cingulate Cortex
Emotional‐Affective Pain
Bushnell CM, et al. Imaging pain in the brain. Journal of Musculoskeletal Pain. 2002;10 (1‐2): 59‐72.
A brain signature that identifies fibromyalgia sufferers with 93 percent accuracy has been discovered by researchers, a potential breakthrough for future clinical diagnosis and treatment of the highly prevalent condition.
An MRI image showing the multivariate brain pattern that predicts fibromyalgia status on the basis of brain activation during multisensory stimulation.
Marina López‐Solà, Choong‐Wan Woo, Jesus Pujol, Joan Deus, Ben J. Harrison, Jordi Monfort, Tor D. Wager. Towards a neurophysiological signature for fibromyalgia. PAIN, 2016; 1 DOI: 10.1097/j.pain.0000000000000707
Neural signature for fibromyalgia may aid diagnosis, treatment
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Descending Antinociceptive SystemLimbic System
Hypo‐ThalamusPeriaqueductal
(PAG) Gray Matter
Nucleus Raphe (NRM) Magnus
Spinal Cord
SEROTONIN (5‐HT)
Limbic system: “emotional brain,” can block pain or facilitate pain
FMS patients may have significant psychological factors affecting the limbic system, which may dampen the DANS.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
From: Hopper, A.-IFM-AIC Presentation 2017
Limbic System
1. Ascending Arousal System
‐ Hypervigilance, sleep disorders
3. DANS
‐ Inhibition of sensory stimuli
5. HPA Axis
- Increased cortisol, ACTH, adrenaline
4. Reticular Formation
‐ Increased skeletal muscle tone
2. Sympathetics & Parasympathetics
‐ “Irritable Everything”
Every Symptom of FMS!
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Early adverse life events change the brain in a sex-dependent manner. Childhood traumas affect women much differently than men resulting in altered brain structure leading to psychological issues as an adult as well as a heightened response to pain. When working with female patients who have depression, anxiety, pain, autonomic/HPA axis dysfunction always take a thorough trauma history which will usually reveal a variety of physical and/or emotional traumas when they were young.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• Serotonin appears to be the key neurotransmitter involved in FMS and sleep
• 3 major functions:– Drives the hypothalamus/HPA axis
– Alters substance P levels and “pain”
– Initiates onset of deep stage 4 sleep
Serotonin, Sleep Disorders, and FM
PAIN
POORSLEEP
FATIGUE
STRESS
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Sleep Dysfunction in FM
• Non‐restorative sleep is a major symptom of FM and correlates with the global achiness/TPI
• Typical EEG pattern of “alpha wave intrusion” during non‐REM delta wave sleep
• Most intense delta activity is in the frontal lobes of the cortex
• Frontal lobe hypoactivity during waking state is associated with inability to concentrate or focus attention (i.e., Fibro‐Fog).
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
At the end of the study, the amber lens group experienced significant (p < .001) improvement in sleep quality relative to the control group and positive affect (p = .005). Mood also improved significantly relative to controls.”
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• In bed by 10pm, up by 7am consistently
• Limit bright/blue‐light and electronics 3 hrs. prior to bed
• Dark quiet bedroom with no pets
• No TV, reading or activities in bedroom (other than two!)
• Prayer and progressive relaxation 30 mins. prior to bed
Sleep Hygiene
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Biofeedback
Heart Rate Variability
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Biofeedback Made Simple at Home
• Decreased serum and platelet serotonin
• Increased substance P in CSF
• Decreased 5‐HIAA and TRP in CSF
• Decreased TRP levels in CSF, platelets, serum
Dadabhoy D, Clauw DJ. Fibromyalgia: different type of pain needing a different type of treatment. Nat Clin Pract Rheumatol. 2006;2:364-372.
Evidence of Serotonin Deficiency in FM
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Biochemistry of Serotonin
TRP5‐HTP
5‐HT5‐HIAA
Excretion
MAO Inhibitors
Re‐uptake of 5‐HT by neurons
SSRIs/SSNRIs
Serotonin and Substance P
Brain 5‐HT Spinal Cord 5‐HT
Spinal Cord Substance P
Brain 5‐HT Spinal Cord 5‐HT
Spinal Cord Substance P
Descending Inhibitory System
FMS = Failure of Descending Inhibitory System?
(Normal)
(Abnormal)
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• Serotonin Modulators– 5‐HTP, melatonin, etc.
– Antidepressant medications – Tricyclics, SSRIs, SSNRIs, MAOIs, etc.
• Stress & Anxiety Management Management– Biofeedback, guided imagery, prayer, meditation, yoga, adrenal
therapy, proper sleep, etc.
– GABA, L‐theanine, inositol, calming adaptogenic botanicals
• Nutritional Supplementation– Mg, malic acid, etc.
Classic FMS Treatment
Rossy L A, Buckelew S P, Dorr N, et al. A meta‐analysis of fibromyalgia treatment interventions. Ann Behav Med. 1999; 21:180‐191.
Sim J, Adams N. Systematic review of randomized controlled trials of non‐pharmacological interventions for fibromyalgia. Clin J Pain. 2002;18:324‐36.
In a randomized, placebo‐controlled study of 200 fibromyalgia patients who were also migraine sufferers, 5‐HTP (400 mg/d) was compared to a tricyclic drug (amitriptyline) and an MAOI (pargyline or phenelzine). The combination of 5‐HTP (200 mg/d) with an MAOI was also evaluated. Patients were treated for a total of 12 months and kept a daily pain dairy by means of a visual analog scale. At the end of the 12‐month trial period, all treatment regimens showed significant improvement over placebo (p < 0.0001), although the combination of 5‐HTP with the MAOI was the most effective. 5‐HTP alone was as effective as the tricyclic or MAOI drugs. No patients withdrew from the study due to side effects; 8% of patients taking 5‐HTP alone reported some degree of stomach upset.
Treatment with 5‐HTP in FMS
Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy. Adv Exp Med Biol. 1996;398:373‐379.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Neurotransmitter Metabolism
If elevated, ask:1. 5‐HTP or L‐Tryptophan
supplements?2. SSRI’s? MAOI’s?
If low, ask:1. Hx depression?2. Insomnia?
• 5‐HTP: 150–300 mg qd in divided dosages with last dose one hour before bed
and/or
• Melatonin: 3–9 mg qd one hour before bed (Sustained‐release preferred)
Simplified Nutraceutical Modulation of Neurotransmitters in Classic FM
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Sceletium tortuosum
• The South African plant Sceletium tortuosum has been used by the indigenous people for hundreds of years for: Relaxation, Stress, Thirst and Hunger (before long hunting trips), soothing infants from: Colic and teething. Modern science has proven its benefits in: increasing mood state, cognitive function, reducing stress, inducing a calm but not sedative effect. It appears to achieve this by a dual inhibition action, by acting both as an SSRI and by its inhibitory effects on PDE4 (phosphodiesterase 4). PDE4 inhibitors are known to possess procognitive (including long‐term memory‐improving), wakefulness‐promoting,] neuroprotective, and anti‐inflammatory effects It has been shown in the research to be non‐addictive, as well as showing no dependency or withdrawal symptoms, after 3 months of continuous use.
Terburg D, Syal S, Rosenberger LA, et al. Acute Effects of Sceletium tortuosum (Zembrin), a Dual 5‐HT Reuptake and PDE4 Inhibitor, in the Human Amygdala and its Connection to the Hypothalamus. Neuropsychopharmacology. 2013;38(13):2708‐2716.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
diagnosticsolutionslab.com
Neurotransmitter Metabolism
High levels:1. Heightened sympathetic reactions in
response to stress2. Neuroblastic Tumor (extreme elevations
in VMA)3. Indication for Adrenal Support
Phenylalanine Tyrosine
Dopamine
Norepinephrine
Epinephrine
Vanilmandelate
Homovanillate
Neurotransmitter Biosynthesis Compound in Urine
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
“Patients with posttraumatic stress disorder (PTSD) have decreased cortisol and increased catecholamine secretion.”
Sympathetic Compensation
Baker DG, et al. Plasma and cerebrospinal fluid interleukin‐6 concentrations in posttraumatic stress disorder [abstract].
Neuroimmunomodulation. 2001;9:209‐217.
This phenomenon can occur in those who may not meet the diagnosticcriteria of PTSD, but also those with “Distressing Life Events.” (See work of Peter Mol, et al)
Is a Sustained Fight/Flight State One Mechanism Behind FM?
Netter FH. The CIBA Collection of Medical Illustrations. Volume 1: The Nervous System. 1977.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Dopamine Melatonin
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Calming Adrenal Botanicals
Ashwagandha(Withania somnifera)15% withanolides
100–200 mg
German chamomile(Matricaria recutita)1.2% apigenin
100‐200 mg
Valerian root(Valeriana officinalis)
100–200 mg
Passion flower(Passiflora incarnate)
100–200 mg
Lemon balm (Melissa officinalis)
100–200 mg
1. Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J of Ethnopharmacol 1999; 64(1): 91-32. Kennedy DO et al. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm).
Psychosomatic Med. 2004;68(4):607-613.3. Groff JL, Gropper SS. Advanced Human Nutrition and Human Metabolism (3rd ed.). Belmont, CA: Wadsworth: 2000
Calming Adrenal Nutrients
L-theanine 100–200 mg
L-taurine 100–200 mg
Phosphatidylserine 50–100 mg
GABA 100 mg
Magnesium-L-threonate 150 mg
Vitamin C (ascorbic acid) 500 mg
Thiamine (B1) 50 mg
Riboflavin (B2) (riboflavin-5-phosphate) 10 mg
Pantothenic acid (vitamin B5) 250 mg
Pyridoxal 5’-phosphate (coenzyme B6) 10 mg
Folate (5-MTHF) 500 mcg
B12 (methyl, hyroxy, adenosyl-cobalamin) 2 mg
1. Hellhammer J et al. Effect of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress:The International Journal on the Biology of Stress. 2004;7(2):119-126.
2. Frosini M et al. Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain. Br J Pharmacol. 2003;138:1163-1171.
3. Driskell JA. Vitamin B6 requirements of humans. Nutr Res 1994; 14: 293-324.4. Groff JL, Gropper SS. Advanced Human Nutrition and Human Metabolism (3rd ed.). Belmont, CA: Wadsworth: 2000
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• Stress management techniques
• Counseling / Therapy
• Promote proper sleep and circadian rhythm
Additional Intervention
Ablin J et al. Treatment of fibromyalgia syndrome: recommendations of recent evidence-based interdisciplinary guidelines with special emphasis on complementary and alternative therapies. Evid Based Complementary AlternatMed, 2013; 485272.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Patients with Widespread Pain and Fatigue
Classic FMS Metabolic-Functional
Medical-Pathologic
Musculo-Skeletal
Differential Diagnosis into Subsets
Complete medical exam and management of the pathology that is causing the pain and fatigue.
• Exam to determine the NMS pain generator(s).
• Chiropractic manual techniques, massage, rehab, modalities, etc.
• Ortho, neuro, or physical medicine referral.
• Limbic system over-activity.
• Sleep disorder must be treated.
• Anxiety, depression, PTSD?
• Psychotropic meds may be needed per MD.
• Cog Behav Therapy, Biofeedback
• Exam to find what metabolic dysfunction is causing the pain and fatigue.
• Vitamin or enzyme deficiency?
• Functional hormone imbalance?
• Food allergies, GI dysbiosis, toxicity, meds?
Schneider M, Brady D, Perle S. J Manipulative Physiol Ther. 2006;29:493-501.
The Great FMS Masqueraders/Imposters
1. Sub‐optimal thyroid function
2. Myofascial pain syndrome
3. Sub‐optimal mitochondrial/Energy metabolism
*Based on my opinion from clinical experience and discussion with colleaguesWho also manage a large number of patients presenting with the FMS label.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Hypothalamus TRH Pituitary
TSH
Thyroid Gland
5% T3
95% T4Liver or
Kidney
rT3
Inactive
(45%)
T3
Active
(35%)
5’‐deiodinase
(Se)
5‐deiodinase
Cell
Nucleus
~ 95%
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Elongated sarcomeres TrP nodule = focus of contracted sarcomeres
Normal sarcomeres
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Therapeutic Nutritional and Herbal Strategy for Muscle Spasm
• Magnesium: 100 mg q4h
• Calcium: 50 mg q4h
• Valerian root: 100 mg q4h
• Passion flower: 200 mg q4h
• Hops: 100 mg q4h
• Kava: 100 mg q4h
Lipoic Acid, CoQ10?
H
H
Both High?
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Energy
Energy
Energy
Energy
All Elevated?
SevereCoQ10
Deficiency
L‐Carnitine Markers
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
• CoQ10: 100‐200 mg bid
• L‐Carnitine: 2.5 gm bid
• D‐Ribose: 2 gm bid
• B‐Complex
• Lipoic Acid: 200 mg qd
• NADH/Nicotinamide riboside: 125 mg qd
• Quality multivitamin‐mineral
• PQQ : 20 mg bid
• Botanicals for mitochondrial biogenesis– Rhodiola, Curcumin, Resveratrol, Green tea, etc.
Mitochondrial Support
Neurological
Oaklander AL, Herzog ZD, Downs H, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. 2013 Jun 5.
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Small Fiber Polyneuropathy
Review
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
All can be associated with fatigue and muscle tenderness
Schneider M, Brady D, Perle S. J Manipulative Physiol Ther. 2006;29:493‐501.
Fibromyalgia Syndrome Clinical Reasoning Guide
“Classic” FMS‐ Sleep disorder
‐ Anxiety
‐ Depression
‐ Alterations of CNS chemistry
‐ Neuro‐endocrine imbalances
Organic‐ Anemia‐ Lyme disease‐ Hypothyroidism‐ Inflammatory arthritides
‐ Dysglycemia‐ Occult carcinoma‐ Multiple sclerosis
Functional‐Mitochodrialdysfunction
‐ Toxicity‐ GI dysbiosis‐ Nutritionaldeficiencies
Musculoskeletal‐ Multiple TrPs‐ Joint dysfunction‐ Muscle imbalance‐ Postural distortion‐ Undiagnosed disc/facet lesions
“Pseudo ‐ FMS”The various disorders
that are misdiagnosed as FMS
1) Organic diseases
2) Functional disorders
3) Musculoskeletal disorders
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Schneider M, Brady DM., Perle SM Differential Diagnosis of Fibromyalgia Syndrome: Proposal of a Model and Algorithm for Patients with the Primary
Symptom of Chronic Widespread Pain. JMPT, 2006;29:493‐501
Dr. David M. Brady-Copyright 2018
Fibromyalgia and Global Pain Syndromes
Patient presents with Sx of widespread pain
& fatigue
Is pain pattern truly the “widespread
pain” of FMS
Is there frank joint swelling? Does this “regional
pain” indicate a musculoskeletal
referred pain pattern?
Lab tests to rule out arthritides:• Lyme Disease
• RA• Lupus, Gout, Ank Spond, etc.
Tests positive?
Box 1Full physical exam, medical
history, and blood/urine tests:
Tests positive?
Does patient exhibit all aspects of
Classic FMS?^^See Note1
^^Note 1: Classic FMS1. True widespread allodynia or hyperalgesia .2. Significant sleep disorder.3. History of significant anxiety/depression/PTSD.4. Fatigue/ neuroendocrine disorders.
Screen for functional and metabolic disorders
***See Note2
Strong likelihood for Classic FMS. Patient needs a team approach:
***See Note2
Suspicion of visceral referred pain requires
complete medical evaluation.Go to Box 1
Musculoskeletal disorders: Determine pain generator(s) and render
appropriate treatment.***See Note2
Patient may have pathology or disease that requires medical
management***See Note2
No
Yes No
No
No
Yes Yes
YesNo
Yes No
***Note 2: Overlapping Disorders1. Having one disorder does not mutually exclude other
disorders, as patients may have an overlap between disorders.
2. Many patients with psychological illnesses and internal disorders have poor nutrition and would benefit from metabolic therapies.
3. Many patients with psychological illnesses have concurrent myofascial trigger points that would benefit from soft tissue therapies.
Yes
Schneider M, Brady D, Perle S. J Manipulative Physiol Ther. 2006;29:493-501.
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