Complex Regional Pain Syndrome - Pathophysiology

Pathophysiology

The pathophysiology of CRPS is not fully understood. Wind-up (the increased sensation of pain with time) and central nervous system (CNS) sensitization are key neurologic processes that appear to be involved in the induction and maintenance of CRPS. There is compelling evidence that the N-methyl-D-aspartate (NMDA) receptor has significant involvement in the CNS sensitization process. It is also hypothesized that elevated CNS glutamate levels promote wind-up and CNS sensitization. In addition, there is experimental evidence that demonstrates NMDA receptors in peripheral nerves. Because immunological functions can modulate CNS physiology, it has also been hypothesized that a variety of immune processes may contribute to the initial development and maintenance of peripheral and central sensitization. Furthermore, trauma related cytokine release, exaggerated neurogenic inflammation, sympathetic afferent coupling, adrenoreceptor pathology, glial cell activation, cortical reorganisation, and oxidative damage (e.g. by free radicals) are all concepts that have been implicated in the pathophysiology of CRPS.