Objectives. Objectives. Fibromyalgia overview 2/13/2013. Disclosure. FM research has flourished since 1980s. Acceptance fibromyalgia as a diagnosis

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Fibromyalgia overview Robert Bennett M.D. Professor of Medicine Mdii and Nursing OHSU Disclosure Research support : Forest, Jazz, Pfizer Advisory Boards: Lilly, Jazz Speaker Bureaus: None Objectives Objectives 1. What is the current status of FM? 1. What is the current status of FM? 2. Pathophysiology of FM 2. Pathophysiology of FM 3. Management overview 3. Management overview FM research has flourished since 1980s Acceptance fibromyalgia as a diagnosis 1,600 1,200 800 400 0 NLM fibromyalgia references in 5 year increments Citations as of Sept 2012: All mentions to 7,006 Titles & abstracts 5,854 Titles only 4,277 National Institutes of Health American Medical Association Mayo clinic website Social Security Disability Veterans Administration World Health Organization ICO 10, M 79 7 American Academy of Family Physicians American Board of Internal Medicine 1

Who gets fibromyalgia? Women 9:1 History of: Abusive relationships Early onset migraine Injuries / accidents Current pain disorders Depressive disorders Hypermobility PTSD Repetitive activities Chronic infection (Hep C, HIV) Genetic predisposition Differential diagnosis of FM Early stages of inflammatory arthritis Polymyalgia rheumatica Drugs (statins) Inflammatory mopathies myopathies Post infectious syndromes Endocrine disorders Osteomalacic myopathy Myofascial pain syndromes Comorbidities associated with fibromyalgia Depression Irritable bowel syndrome Restless leg syndrome Overactive bladder syndrome Vulvodynia, pelvic pain syndrome TMJ syndrome Migraine Chronic daily headaches Non cardiac chest pain Primary Raynaud s phenomenon Diagnosing fibromyalgia The 1990 ACR Classification Criteria New Diagnostic Criteria? Problems with 1990 ACR criteria Fibromyalgia definition: 1. Symptoms for at least 3 months 2. Widespread pain 3. Pain at least 11 from 18 TPs 1. Only defines FM in terms of pain 2. A TP score of 11 without other symptoms is suspect 3. Tender point evaluation is partly subjective 4. Skills vary in TP evaluation 5. Full TP evaluation is often not done 6. A patient can be declared as not having FM 7. A TP examination can be faked 2

New Diagnostic Criteria? Proposed Diagnostic Criteria? 1. Number of pain locations (out of 18): A patient satisfies modified ACR 2010 preliminary Shoulder girdle, Lt. Hip (buttock, trochanter), Lt. Jaw, Lt. Upper Back diagnostic Shoulder girdle, criteria Rt. Hip (buttock, if: trochanter), Rt. Jaw, Rt. Lower Back Upper Arm, Lt. Upper Leg, Lt. Chest Neck, Upper Arm, Rt. Score Upper = Leg, 0 18 Combine scores Rt. Abdomen, Lower Arm, Lt. Lower Leg, Lt.Lower Arm, Rt. Lower Leg, Rt. 1. Pain locations 7 and from Symptom 2 and 3Severity Score 5 0 = No problem 2. Symptom Severity (over past or week): 1 = Slight or mild problems 2. Fatigue Pain locations between 3 6 and 2 = Moderate; Symptom considerable Severity Waking un refreshed 3 = Severe; pervasive problems Score Cognitive symptoms 9 Symptom severity index Score = 0 9 Also: 3. Symptom Symptoms Prevalence must (over have past 6 months): been present at a similar Headaches 0 = Not experienced level for 3 months and the patient does not Pain or cramps in lower abdomen 1 =Was experienced Depression have a disorder that would explain the pain. Score = 0 3 Pathophysiology of fibromyalgia It s all in your head Unexplained symptoms are often still viewed as psychogenic in origin: Somatization Hypochondriasis Masked depression etc. Abnormal sensory processing in FM 1. Hyperalgesia / allodynia 2. Elevated CSF levels of neurotransmitters 3. Temporal summation 4. Enhanced somatosensory potentials (EEG) 5. Increased activity on fmri scans 6. Impaired DNIC 7. Response to centrally acting drugs 3

fmri imaging of cerebral pain responses Regions in which the activity was significantly greater in FM patients than controls at a left thumb pressure of 2.3 kg/cm 2 ARTHRITIS & RHEUMATISM Vol. 46, No. 5, May 2002, pp 1333 1343 Functional Magnetic Resonance Imaging Evidence of Augmented Pain Processing in Fibromyalgia Richard H. Gracely, Frank Petzke, Julie M. Wolf, and Daniel J. Clauw At a thumb pressure of 2.3 kg/cm 2 there was significantly greater activation in 12 regions of FM patients compared to controls SPECT in FM without any pain stimulus The two levels of pain regulation Top-down Increased brain activity in areas that are involved in pain processing Guedj E, Eur J Nucl Mol Med, 2006 Bottom-up Increasing Evidence for Defective Pain Descending Inhibitory Pathways in FM Anxiety, aversive memories, cultural context, placebo response, nocebo response Electrical stimulation opioids, NSAIDs, placebo / nocebo response Stress, exercise Opioids, cannabinoids Cholecystokinin, glial activation, 5 HT/ 5 HT PAIN Diffuse noxious inhibitory control (DNIC) Demonstrated impaired DNIC in FM patients Opioids, TCAs, SNRIs α 2 agonists, 5 HT 3 From: Ossipov, Dussor and Porreca JCI 2010 4

Activation of descending inhibitory pain system Impulses arise in nuclei of brainstem Activation of descending facilitatory pain system Impulses arise in nuclei of brainstem Decreased activity in ascending neuron Increased activity in ascending neuron Objectives 1. What is the current status of FM? 2. Pathophysiology of FM 3. Management overview A multidisciplinary approach Treating fibromyalgia Primary care Rheumatologist Pain specialist Psychatrist Psychologist Exercise Sleep specialist Spouse Children Parents Employer Friends Biofeedback therapist Acupuncturist Chiropracter Therapist / counselor 5

Peripheral pain generators Centrally acting pain medications approved by FDA Osteoarthritis Peripheral pain generators Myofascial trigger drive central sensitization points Pregabalin Anticonvulsant α 2 δ ligand Duloxetine Antidepressant Balanced SNRI Milnacipran Antidepressant Balanced SNRI FDA-approved for fibromyalgia pain at 300-450 mg/day taken in FDA-approved for treatment of fibromyalgia pain at 60 mg/day: FDA-approved for fibromyalgia management at 100-200 mg/day taken in divided doses BID: Neurofeedback for pain modulation Neuroscience. 2013, 231:102 10 Cortical stimulation modalities Pain Medicine 2012; 13: 115 124 Self-regulation of acute experimental pain with and without biofeedback using spinal nociceptive responses Arsenault, Piche and Rainville Départment de Psychologie, Université de Montréal, Montréal, QC, Canada Sleep disturbance Impaired sleep modulates pain processing SLEEP 2007;30(4):494 505 Alpha/delta sleep Frequent sleep disruptions q p p cause a reduction in the descending inhibitory control system for pain 6

Neurofeedback for sleep disorders Appl Psychophysiol Biofeedback. 2011, 36(4):251 64 Neurofeedback for insomnia: a pilot study of Z-score SMR and individualized protocols Hammer, Colbert, Brown and Ilioi Department of Psychophysiology, Helfgott Research Institute, National College of Natural Medicine, 049 SW Porter Street, Portland, OR 97201 4848, USA Lastly remember FM comorbidities Depression Irritable bowel syndrome Restless leg syndrome Overactive bladder syndrome FM comorbidities also drive central sensitization Vulvodynia, pelvic pain syndrome TMJ syndrome Migraine Chronic daily headaches Non cardiac chest pain Primary Raynaud s phenomenon 7