Complex regional pain syndrome is a disease of the central nervous system

Abstract

Complex regional pain syndrome (CRPS) is clinically characterized by pain, abnormal regulation of blood flow and sweating, edema of skin and subcutaneous tissues, trophic changes of skin, appendages of skin and subcutaneous tissues, and active and passive movement disorders. It is classified into type I (previously reflex sympathetic dystrophy) and type II (previously causalgia). Based on multiple evidence from clinical observations, experimentation on humans, and experimentation on animals, the hypothesis has been put forward that CRPS is primarily a disease of the central nervous system. CRPS patients exhibit changes which occur in somatosensory systems processing noxious, tactile and thermal information, in sympathetic systems innervating skin (blood vessels, sweat glands), and in the somatomotor system. This indicates that the central representations of these systems are changed and data show that CRPS, in particular type I, is a systemic disease involving these neuronal systems. This way of looking at CRPS shifts the attention away from interpreting the syndrome conceptually in a narrow manner and to reduce it to one system or to one mechanism only, e.g., to sympathetic-afferent coupling. It will further our understanding why CRPS type I may develop after a trivial trauma, after a trauma being remote from the affected extremity exhibiting CRPS, and possibly after immobilization of an extremity. It will explain why, in CRPS patients with sympathetically maintained pain, a few temporary blocks of the sympathetic innervation of the affected extremity sometimes lead to long-lasting (even permanent) pain relief and to resolution of the other changes observed in CRPS. This changed view will bring about a diagnostic reclassification and redefinition of CRPS and will have bearings on the therapeutic approaches. Finally it will shift the focus of research efforts.

Post-traumatic complex regional pain syndrome: clinical features and epidemiology

“…Multiple mechanisms are considered to play a role in the generation and maintenance of CRPS: biofeedback from autonomic nervous system, alterations of central nervous system, neurogenic inflammation and immunological mechanisms (2,3). It is generally considered that the inflammation process may be the major mechanism because the initial signs of CRPS represent the typical signs of inflammation (4,5).…”

Neuropathic Pain and Deep Brain Stimulation

“…A recent paradigm shift towards central brain reorganization with autonomic dysfunction as the mechanism underlying complex regional pain syndromes support the treatment for brachial and lumbar plexus injuries, and stump pain after amputation, as well as phantom limb pain [74][75][76][77][78].…”

Complex Regional Pain Syndrome - Diagnosis, Treatment and Future Perspectives

“…31 This process is triggered by the release of SP, CGRP and glutamate after tissue damage, which in turn activate the normally dormant N-methyl-D-aspartic acid (NMDA) receptor. 32 Elevated levels of glutamate found in the serum and cerebrospinal fluid of patients with CRPS are suggestive of the involvement of NMDA receptor responses.…”