Complex regional pain syndrome (CRPS) is a highly enigmatic syndrome typically developing after injury or surgery to a limb. Severe pain and disability are common amongst those with chronic forms of this condition. Accumulating evidence suggests that CRPS may involve both autoinflammatory and autoimmune components. In this review article evidence for dysfunction of both the innate and adaptive immune systems in CPRS is presented. Findings from human studies in which cytokines and other inflammatory mediators were measured in the skin of affected limbs is discussed. Additional results from studies of mediator levels in animal models are evaluated in this context. Similarly, the evidence from human, animal and translational studies of the production of autoantibodies and the potential targets of those antibodies is reviewed. Compelling evidence of autoinflammation in skin and muscle of the affected limb has been collected from CRPS patients and laboratory animals. Cytokines including IL-1beta, IL-6, TNFalpha and others are reliably identified during the acute phases of the syndrome. More recently, autoimmune contributions have been suggested by the discovery of self-directed pain-promoting IgG and IgM antibodies in CRPS patients and model animals. Both the autoimmune and autoinflammatory components of CRPS appear to be regulated by neuropeptide containing peripheral nerve fibers and the sympathetic nervous system. While CRPS displays a complex neuroimmunological pathogenesis, therapeutic interventions could be designed targeting autoinflammation, autoimmunity or the neural support for these phenomena.
View details for PubMedID 30124090