Fibromyalgia: New Hope and New Pharmaceuticals
Fibromyalgia may produce pain ranging from mild to severe and is now among the major reasons for referral to a pain center. Until now, few therapies have proven effective but several new agents provide pain relief in most cases. This update reviews both the old and new pharmacologic agents used to treat fibromyalgia.
Despite the introduction of the term fibrositis in 1904 by Gower,1 progress in understanding FMS has been slow. However, recent innovative strategies and broader investigation of its cause, beyond a myopic focus on psychiatric or musculoskeletal research, have finally led to a new expectation of improved treatment outcome.
Firm confidence in a diagnosis is essential before formulating and implementing an effective treatment strategy in any medical condition. For many clinicians, the diagnosis of FMS remains confusing despite validated criteria published by the American College of Rheumatology in 1990 (See Table 1).2 While specific tenderness, or tender points, have been promoted as diagnostic evidence of this disorder, honest debate and, at times, unruly skepticism, is evident even among rheumatologists. While helpful as inclusion criteria for research studies, fibromyalgia tender-point intensity can still vary from day to day in clinical practice, leading to diagnostic uncertainty. Nevertheless, clinicians can readily recognize and attempt to treat the common presentation of chronic, unexplained, widespread pain, tenderness, and fatigue of fibromyalgia.
History of Widespread Pain. Definition:
Pain in 11 of 18 Tender Point Sites on Digital Palpation. Definition:
There is no consensus regarding pathogenesis, but an abnormality of centrally mediated pain processing has gained greater acceptance.3 Functional magnetic resonance imaging (fMRI)4 and pain-testing studies5 have significantly strengthened this concept of centrally amplified pain perception. Observations of abnormal sleep-stage architecture6 and induction of FMS symptoms with specific disruption of deep, non-rapid eye movement (nREM), stage IV sleep,7 have encouraged consideration of how sleep affects a variety of CNS functions influencing pain, fatigue and cognitive behavior. Sophisticated measurements of autoimmune regulation with validated tools, including heart rate variability and tilt-table testing, have increased the awareness that patients with FMS fail to maintain normal sympathetic homeostasis.8-14 In turn, perturbed sleep, psychiatric arousal (e.g., post-traumatic stress disorder, bipolar disorder and anxiety disorder), peripheral vasomotor tone, cardiac rhythm, and bowel motility focus future research directly on new autonomic mechanisms that may lead to an improved understanding of FMS.
Almost 85% of FMS cases occur in women, but men are often undiagnosed. In fact, the divergent presentation of FMS in men compared with women has been well reported.15 Pain and muscular spasm are generally more diffuse and vague in men. It appears that the hallmark diagnostic finding in FMS, 11 of 18 specific tender points, becomes apparent to the clinician and male patients much later in its clinical course. Response rates (RRs) to a variety of pharmacologic options are also less robust in men. The cause of these gender differences in presentation and response is uncertain, but may relate to behavioral differences, comorbidities, or hormonal variations, including clinically amenable testosterone deficiency in men receiving chronic opioids.