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.

Osteosarcoma-Induced Pain Is Mediated by Glial Cell Activation in the Spinal Dorsal Horn, but Not Capsaicin-Sensitive Nociceptive Neurons: A Complex Functional and Morphological Characterization in Mice

“…New research suggests that inflammatory and immune cells infiltrate damaged peripheral nerves, potentially releasing a range of cytokines and growth factors. These substances could play a role in both the onset and persistence of neuropathic pain [62].…”

NMDA Receptors Regulate Oxidative Damage in Keratinocytes during Complex Regional Pain Syndrome in HaCaT Cells and Male Rats

“…Furthermore, it is worth noting that acute stressors, such as significant nociceptive stimuli and surgical procedures, can elicit a hyperinflammatory response and potentially trigger the development of CRPS following trauma [4]. Although the mechanisms of CRPS are complex and remain poorly understood, potential mechanisms are believed to involve peripheral and central sensitization, systemic inflammation, autonomic dysfunction, and neuroinflammation [5][6][7][8][9]. Given that the current treatment options for CRPS are limited, a more comprehensive understanding of the underlying mechanisms would make a significant contribution toward the development of novel therapeutic strategies.…”

Mechanisms of complex regional pain syndrome

“…Recent studies have begun to unravel its multifaceted nature, highlighting autoimmune mechanisms and neuroimmune interactions. We have recently reviewed the role of neuroinflammation in CRPS (1). Here we aim to provide a comprehensive review of the enigmatic nature of CRPS, setting the stage for further exploration into its complexities and advancements in understanding and treating this debilitating condition.…”