Complex regional pain syndrom : Physiopathology and mechanisms

Understanding of the pathophysiological features of CRPS has progressed over the past decade. CRPS-associated regional vasomotor and sudomotor changes are thought to be caused by both neurogenic inflammation and abnormal regional autonomic activation. Neurogenic inflammation is caused by the antidromic release of neuropeptides, including substance P and calcitonin gene-related peptide, from sensory nerve endings, which causes swelling, warmth, redness, nail and hair growth, and hyperhidrosis. Abnormal regional autonomic activation comes through an abnormal responsiveness of adrenoceptors that may independently contribute to temperature regulation, skin-color changes, swelling, sweating, and nail and hair growth. In the affected skin of patients with early CRPS, the concentration of inflammatory mediators is increased and neuropeptides are abnormally active. CRPS has been shown to be associated with specific microbiome signatures and patients with early CRPS as well as those with persistent CRPS harbor circulating autoreactive IgM and IgG antibodies. White male persons with CRPS may have a permissive (facilitating but not causing the development of disease) genetic background. In persistent CRPS, widespread skin sensitivity may occur, which is consistent with a possible contribution of central sensitization (increased responsiveness of neurons in the central nervous system to their normal or subthreshold input), although this mechanism has not been directly proved.