Fibromyalgia - The Sound of Distant Thunder
Fibromyalgia - The Sound of Distant Thunder
Few clinical entities invite the kind of controversy that swirls around fibromyalgia (FM). The traditional conceptualization of the disorder as a musculoskeletal condition stems primarily from the work of Sir William Gowers, who, in 1904, proposed that chronic widespread pain results from diffuse inflammation of fibrous connective tissues. Subsequent analyses failed to demonstrate such inflammation and, to date, no peripheral tissue pathology has been described that might convincingly explain patient symptoms. Although pain is the hallmark of FM, patients are typically afflicted by a constellation of other symptoms, many of which suggest neurological involvement. While standard laboratory evaluations and medical imaging routinely fail to demonstrate abnormalities, research has revealed disturbances in neuroendocrine and autonomic function, in cerebrospinal fluid concentrations of multiple neurochemicals, and, most importantly, in brain function and activity. Thus, while the search for peripheral pathology to characterize the disorder remains an essentially quixotic effort, there is increasing evidence that the primary pathology in FM lies within the central nervous system.
Overview of Fibromyalgia
FM is a common condition with an estimated prevalence of 2% of the general population (3.4% for women, 0.5% for men). Although all ages are affected, the prevalence increases with age, reaching greater than 7% in women aged 60 79 years. Given that the vast majority of FM patients are female, there is suspicion that gender-specific factors (e.g. ovarian steroids) may play a role in its development. In the US alone, FM is thought to affect as many as 10 million people, yet despite its prevalence, there are currently no medications indicated for the treatment of the disorder.
While the phenomenon of chronic widespread pain appears in the medical literature as early as the beginning of the last century, diagnostic criteria for classification and research purposes were not formalized until 1990, when the American College of Rheumatology published the consensus of a multicenter criteria committee. Accordingly, FM is classified by the presence of widespread pain in a symmetrical, primarily axial, distribution for a minimum of three months and the demonstration of tenderness to light palpation (4kg force) in at least 11 of 18 anatomically defined tender points. While the value of these criteria to the diagnosis and management of the disorder is the subject of enduring debate, they are the de facto diagnostic criteria in the clinical setting.
Besides the presence of chronic widespread pain, patients were also noted in the original classification document to commonly experience symptoms involving multiple bodily systems, including chronic fatigue and sleep disturbances, disturbed bowel function, genitourinary problems, and such allergic phenomena as persistent sinus congestion. A more recent document the Canadian Clinical Case Definition also places increased emphasis on neurological phenomena associated with the disorder, which include dysautonomia, nondermatomal paresthesias, headache, temporospatial dysmetria, restless legs syndrome, and cognitive dysfunction characterized by impaired concentration and shortterm memory consolidation, impaired speed of performance, inability to multi-task, and frequent cognitive overload.
Models of Fibromyalgia Pathology
Among the obstacles to the development of effective treatments for FM is a persistent lack of understanding regarding the pathology underlying its chief symptom, i.e. chronic widespread pain. Broadly speaking, somatosensory perception may be conceptualized as involving three interrelated neurological processes: flow of afferent somatosensory information from the peripheral to the central nervous system; supraspinal processing of somatosensory information; and outflow of efferent signals via descending spinal tracts that modulates afferent drive by inhibiting or facilitating somatosensory input. A disruption of any one of these might ostensibly result in the subjective experience of increased pain.
Peripheral sensitization of nociceptive neurons has been postulated as a potential mechanism underlying the pain of FM. For example, compromise of the vagus nerve, which produces a disruption of parasympathetic tone, results in an adrenergic-dependant reduction in pain thresholds. Intriguingly, autonomic imbalance characterized by sympathetic dominance has been demonstrated in FM, which has led to the proposition that FM pain may stem from disruption of normal autonomic function. Sensitization of the peripheralspinal interface (i.e. the dorsal root ganglia and spinal dorsal horn) secondary to increased activity of spinal n-methyl-d-aspartate (NMDA) receptors has been demonstrated to result in the development of chronic pain. The suggestion has thus been raised that FM might likewise result from sensitization of central NMDA receptors. However, while initial experimental evidence appeared to support this hypothesis, subsequent re-evaluation of the experimental phenomena upon which the proposition was originally based appears to make it unlikely that sensitization of spinal NMDA receptors is the source of pain in FM.
