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Fibromyalgia: Explaining Unexplained Pain

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from WebMD Scientific American® Medicine Posted 02/23/2004 John Winfield, MD

Fibromyalgia is a syndrome characterized by generalized pain, fatigue, disturbed sleep, and numerous unexplained somatic complaints that is present in at least 5% of the general adult population (mostly women) in Western countries. With the exception of painful tender points, the clinical, routine laboratory, and imaging evaluations in uncomplicated fibromyalgia are normal, which has led some to assert that this syndrome either does not exist or is strictly a psychological disorder.

Fibromyalgia largely overlaps with chronic fatigue syndrome (CFS), irritable bowel syndrome (IBS), temporomandibular joint pain, "myofascial pain syndrome," and other regional pain syndromes. Best classified at the present time as one of a series of "symptom-based conditions" or "functional somatic syndromes," recent research in the neurophysiology and neuroendocrinology of pain demonstrates that fibromyalgia is not simply a psychological disorder.

Pain, the hallmark of this syndrome, diffusely radiates from the axial skeleton and is localized to muscles and muscle-tendon junctions of the neck, shoulders, hips, and extremities. Pain thresholds are reduced, and many patients exhibit generalized allodynia, defined as pain from normally nonpainful stimuli. Although depression, anxiety, and other psychiatric comorbidities are commonly present, the pain and fatigue associated with fibromyalgia have demonstrable pathophysiologic bases.

At one level, fibromyalgia can be viewed from the perspective of Engel's biopsychosocial model of chronic illness.[1] According to this model, pain, fatigue, and other symptoms arise and persist from an interplay of a series of biologic, psychological, and sociologic variables. Gender, poor sleep, neuroendocrine and autonomic dysregulation related to chronic stress, and abnormal processing of afferent input to the central nervous system have clearly been identified as important biologic variables. The most dramatic laboratory abnormality is a consistently elevated level of substance P in the cerebrospinal fluid, which is found in about 80% of fibromyalgia patients. Social and behavioral research is providing crucial insight into the role of cognitive-behavioral variables, such as pain beliefs and attributions, depression, anxiety and perceived self-efficacy for pain control, and environmental and sociocultural variables, such as a history of childhood sexual abuse, which appears to be a particularly important antecedent.

Evidence for therapeutic efficacy in fibromyalgia based on randomized, controlled trials has been difficult to obtain because of current poor understanding of etiopathogenesis, symptom complexity, and lack of consensus regarding nosology and clinically meaningful outcome measures. Consequently, much current treatment is based on proposed, rather than established, models of pathophysiology. Nevertheless, the available data clearly suggest that symptoms of pain, fatigue, nonrestorative sleep, depression, and anxiety respond to a multifaceted therapeutic approach combining pharmacologic and nonpharmacologic (physical, psychological, and behavioral) treatments. The goal is palliation of symptoms, not cure.

Abundant evidence from randomized, controlled trials supports the efficacy of physical modalities, especially graded aerobic exercise, various stress-management approaches, and judicious use of pharmacologic agents. Conversely, many widely used nonpharmacologic treatments (e.g., "trigger point" injections, botulinum toxin [Botox], acupuncture, and ultrasound) have not shown significant benefit beyond nonspecific, placebo-related effects. Sleep disturbances should be treated aggressively, both by attention to good sleep hygiene and by appropriate use of the many new hypnotic and anxiolytic medications. Selective serotonin reuptake inhibitors benefit both associated depression and the diffuse pain and other symptoms in fibromyalgia. Persistent fatigue responds to modafinil (FDA approved for narcolepsy) or tropisetron, a 5-HT3 receptor antagonist. First-line agents for the diffuse pain in fibromyalgia continue to be the low-dose tricyclic antidepressants (TCAs), often in combination with a centrally acting muscle relaxant, such as cyclobenzaprine. Marked allodynia and hyperalgesia often respond to the addition of an antiepileptic drug, such as gabapentin or pregabalin. Topical capsaicin also is useful when applied to painful areas with gentle massage. Other drugs that have effects on the abnormal central nociceptive processing in fibromyalgia include mexilitine (sodium channel blocker), clonidine (centrally acting antiadrenergic), and tropisetron. In rare cases, patients may require opioids to improve quality of life and maintain daily functioning.

The prevalence of fibromyalgia, its impact on quality of life and functional capacity, and its attendant personal and societal costs impel the medical community to take this illness seriously. Recent advances in our understanding of chronic "unexplained" pain and its treatment provide optimism for the future.

John Winfield, MD, University of North Carolina at Chapel Hill School of Medicine. Source: WebMD Scientific American® Medicine 2004. © 2004 WebMD Inc. All rights reserved.

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