Passive transfer of fibromyalgia symptoms from patients to mice

Fibromyalgia syndrome (FMS) is a chronic pain condition characterized by widespread pain, augmented pain sensitivity to mechanical pressure and cold temperatures (1–4), as well as fatigue and emotional distress (5–7). The prevalence of FMS is at least 2% (8), and approximately 80% of FMS patients are women. The prevalence rises to 10%–30% among patients diagnosed with autoimmune rheumatological conditions (9, 10), and FMS is thus one of the most common chronic pain conditions. The etiology and pathophysiology of FMS are not completely understood (11) and the current treatment strategies for FMS rely mainly on lifestyle changes, physical exercise, and drug therapy with antidepressants and anticonvulsants. Unfortunately, the modest efficacy of the available therapies in most patients leaves an enormous unmet clinical need (12, 13). The animal models that have been used for experimental studies of FMS have uncertain translational relevance and rely on local repeated intramuscular injections of acid (14) or systemic depletion of monoamines by reserpine treatment (15). The development of novel, mechanism-based therapies has been hampered by the limited understanding of the basis of FMS.

The increased polymodal pain sensitivity experienced by FMS patients (1, 16) is associated with altered pain processing in the central nervous system (11), dysfunctional descending pain modulation (17, 18), and structural and functional changes in the brain (19–21). FMS is also associated with abnormalities in peripheral sensory afferents, such as spontaneous activity and sensitization of C-fibers, and loss of epidermal innervation (22, 23). Altered levels of inflammatory and immunoregulatory cytokines have also been reported in FMS patients. Although these alterations do not follow a consistent pattern (24, 25), they may suggest that immune processes are dysregulated in patients. These observations, together with the markedly increased prevalence of FMS among patients with autoimmune rheumatological conditions (9, 10), and demonstrations that less common (26, 27) and very rare chronic pains (28) are caused by autoantibodies, led us to hypothesize that FMS may have an autoimmune basis. Here we have investigated the possibility that autoreactive IgG is responsible for several key symptoms of FMS, by examining whether these can be transferred to mice by administration of IgG purified from FMS patients, and by assessing the tissue localization of IgG after passive transfer.