Fibromyalgia Syndrome: Guidelines for Effective Care

Fibromyalgia syndrome (FMS) is a chronic condition characterized by multiple symptom domains: pain, fatigue, sleep disturbance, mood disturbance, and quality-of-life and function impairment.¹ Other common associated conditions and symptoms include irritable bowel syndrome, irritable bladder syndrome (interstitial cystitis), tension and migraine headache, cognitive dysfunction ("fibrofog"), stiffness, paresthesias, and restless legs syndrome. Optimal management of FMS involves multimodal treatment approaches that address the various symptom domains that patients may experience.

Over the past century, FMS has had several monikers, such as "fibrositis," but it was not until 1990 that the American College of Rheumatology (ACR) established classification criteria. The criteria defined FMS as a condition in which widespread pain has been present in at least 11 of 18 anatomically specific tender points for at least 3 months.²

The ACR classification criteria were intended to be used for research studies, but increasingly they have been used as diagnostic criteria in practice. This is problematic. Although the tender point examination helps physicians discriminate FMS as a condition characterized by augmented tenderness, an increased number of tender points is associated with female sex and "distress." This criterion lacks high specificity and excludes some patients with chronic widespread pain who do not fulfill the tender point criteria but whose pain probably arises from the same pathophysiology.^3,4

Much remains that is not understood about the pathogenesis and proper classification of FMS, partly because clear-cut biomarkers and objective treatment parameters are lacking; this sometimes leads to physician skepticism and patient frustration. However, an increased awareness of the prevalence, clinical pattern, and pathophysiology of FMS—rooted in neural dysregulation, particularly "central sensitization"—is facilitating more prompt diagnosis and appropriate patient care.

Here, following a brief overview of the epidemiology and pathophysiology of FMS, we provide an update on the latest management approaches.

EPIDEMIOLOGY
The prevalence of FMS, which occurs primarily in women, is estimated at 2% to 5% of the US population.⁵ FMS may exist on its own, or it may be associated with other painful conditions, such as degenerative or inflammatory arthritis and low back pain.⁶ Indeed, the disorder is reported to occur in up to 25% of patients who have rheumatoid arthritis or lupus.⁷

FMS also may occur with other conditions that are considered to be somatic syndromes—ie, symptomatic conditions that do not have demonstrable structural changes—and it may share genetic predisposition and pathophysiological mechanisms with them.⁷ Examples include irritable bowel syndrome, irritable bladder syndrome, and temporomandibular joint syndrome. Some patients ascribe the onset of FMS to specific "triggers," including viral illness (eg, Lyme disease or hepatitis C), physical trauma, and major emotional stress.⁷

PATHOPHYSIOLOGY: TARGETS OF THERAPY
In the 1970s, Moldofsky and colleagues⁸ conducted pioneering sleep physiology studies that suggested the presence of sleep architecture abnormalities in patients with FMS. Since then, numerous studies have centered the pathophysiology of FMS in the CNS. Earlier concepts about FMS having an inflammatory component or being a disorder of peripheral muscle largely have been set aside.⁶

It has been observed that patients with FMS perceive more pain from nonpainful stimuli (allodynia) than do healthy controls and experience greater pain from painful stimuli (hyperalgesia).⁹ Functional MRI studies conducted by Gracely and associates¹⁰ have provided dynamic neuroimaging confirmation of this observation. A unifying concept is that increased pain sensitivity is the result of dysregulation of neuropeptide and neuroreceptor physiology in the ascending and descending spinal cord pain signaling pathways as well as in brain processing centers (Figure).

Central sensitization connotes amplified ascending nerve activity and receptor fields, part of which is the phenomenon of temporal summation, or "wind-up," in which stimuli after an initial pain stimulus are experienced as more intensely painful.⁷ This phenomenon is at least partly the result of dysregulation of the N-methyl d-aspartic acid (NMDA) receptors in the dorsal horn in patients with FMS. Russell and coworkers11 noted increased amounts of pronociceptive substance P in the cerebrospinal fluid of patients who had FMS compared with controls. Therefore, treatments known to down-regulate such pronociceptive neuropeptides may be beneficial for patients with FMS.