Etiology and pathophysiology of fibromyalgia syndrome and chronic widespread pain

Objective. To write a systematic review on the etiology and pathophysiology of the fibromyalgia syndrome (FMS) and of chronic widespread pain (CWP). Methods. An interdisciplinary level-3 guideline (i.e. systematic literature search and assessment, logic analysis, formal consensus procedure) for the diagnosis and therapy of FMS was created in cooperation with 10 medical and psychological societies and 2 patient self-help organizations. A literature search was performed covering all available review articles on the etiology and pathophysiology of FMS and CWP using the Cochrane Collaboration Reviews (1993-12/2006), Medline (1980-2006), PsychInfo (1966-12/2006), and Scopus (1980-12/2006). For the assignment of evidence classes the system of the Oxford Centre for Evidence-Based Medicine was applied. Consensus was achieved by a multi-step nominal group procedure. Results. FMS aggregates in families (evidence level 2c). Physical and psychological stress at the workplace are risk factors for the development of CWP and FMS. Affective disorders are risk factors for the development and maintenance of FMS. Operant learning mechanisms and sensitization are risk factors for the chronification of FMS (evidence levels 2b). Several factors are associated with the pathophysiology of FMS, but the causal relationship is unclear. This includes alterations of central pain pathways, hyporeactivity of the hypothalamus-pituitary-adrenal axis, increased systemic pro-inflammatory and reduced anti-inflammatory cytokine profiles and disturbances in the dopaminergic and serotonergic systems. Conclusions. FMS is the common final product of various etiological factors and pathophysiological mechanisms.