The Role of Neuroinflammation in Complex Regional Pain Syndrome: A Comprehensive Review

Abstract

Complex Regional Pain Syndrome (CRPS) is an excess and/or prolonged pain and inflammation condition that follows an injury to a limb. The pathogenesis of CRPS is multifaceted that remains incompletely understood. Neuroinflammation is an inflammatory response in the peripheral and central nervous systems. Dysregulated neuroinflammation plays a crucial role in the initiation and maintenance of pain and nociceptive neuronal sensitization, which may contribute to the transition from acute to chronic pain and the perpetuation of chronic pain in CRPS. The key features of neuroinflammation encompass infiltration and activation of inflammatory cells and the production of inflammatory mediators in both the central and peripheral nervous systems. This article reviews the role of neuroinflammation in the onset and progression of CRPS from six perspectives: neurogenic inflammation, neuropeptides, glial cells, immune cells, cytokines, and keratinocytes. The objective is to provide insights that can inform future research and development of therapeutic targets for CRPS.

Keywords:

• complex regional pain syndrome
• neuroinflammation
• neurogenic inflammation
• glial cells
• keratinocytes

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (82271262 to LX), National Institutes of Health of USA (CA228039 to JX; NS127258 to JC), VeloSano Pilot Award, Steve and Melody Golding Foundation (to JX).