Update on the pathogenesis of complex regional pain syndrome: Role of oxidative stress

Abstract

Complex regional pain syndrome (CRPS) is a chronic inflammatory pain syndrome that affects one or more extremities of the body. It is characterized by burning pain and abnormalities in the sensory, motor, and autonomic nervous systems. This review illustrates how oxidative stress and nuclear factor erythroid 2-related factor (Nrf2) activation might contribute to understanding the etiopathogenesis of CRPS. The precise cause of CRPS remains unclear, and current treatments are not effective in many patients. The mechanism underlying CRPS may differ across patients and even within a single patient over time. Inflammatory and neuronal mechanisms have been suggested as key contributors to CRPS. Recent evidence demonstrates that oxidative stress is associated with clinical symptoms in patients with CRPS-I. Oxidative stress plays a key role in CRPS pathogenesis. The Nrf2 factor is a master regulator of the transcription of multiple antioxidants, which protects against oxidative stress and inflammation by inducing antioxidant and detoxifying genes through binding with an antioxidant response element. It has antinociceptive effects against inflammatory pain in an animal model. This review summarises the effect of oxidative stress and mitochondrial dysfunction in the pathogenesis of CRPS. It also addresses the question of whether there is a potential role for Nrf2 (activated by pharmacological or nutritional activators) in alleviating the clinical features of CRPS or preventing its progression.