Complex regional pain syndrome (CRPS) is a painful condition, which arises in a limb after trauma. CRPS can profoundly affect patients' quality of life, and there is no cure. CRPS is associated with limb-confined sensory, motor, skin, bone and autonomic abnormalities. Recent research has shown that some patients respond to treatment with immunoglobulins, and that a majority have IgG serum-autoantibodies directed against, and activating autonomic receptors. CRPS serum-IgG, when transferred to mice elicits abnormal behaviour. These results suggest that CRPS is associated with an autoantibody-mediated autoimmune process in some cases. CRPS has unusual features, including a non-destructive, and regionally-confined course. We propose that CRPS constitutes a prototype of a new kind of autoimmunity, which we term 'IRAM' (injury-triggered, regionally-restricted autoantibody-mediated autoimmune disorder with minimally-destructive course). Understanding autoimmune contribution to CRPS should allow the exploration of novel treatment modalities in the future. Additional 'functional' disorders, painful or painless may be autoimmune in nature.
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