Mechanisms and Therapeutic Prospects of Microglia-Astrocyte Interactions in Neuropathic Pain Following Spinal Cord Injury

Neuropathic pain is a prevalent and debilitating condition experienced by the majority of individuals with spinal cord injury (SCI). The complex pathophysiology of neuropathic pain, involving continuous activation of microglia and astrocytes, reactive gliosis, and altered neuronal plasticity, poses significant challenges for effective treatment. This review focuses on the pivotal roles of microglia and astrocytes, the two major glial cell types in the central nervous system, in the development and maintenance of neuropathic pain after SCI. We highlight the extensive bidirectional interactions between these cells, mediated by the release of inflammatory mediators, neurotransmitters, and neurotrophic factors, which contribute to the amplification of pain signaling. Understanding the microglia-astrocyte crosstalk and its impact on neuronal function is crucial for developing novel therapeutic strategies targeting neuropathic pain. In addition, this review discusses the fundamental biology, post-injury pain roles, and therapeutic prospects of microglia and astrocytes in neuropathic pain after SCI and elucidates the specific signaling pathways involved. We also speculated that the extracellular matrix (ECM) can affect the glial cells as well. Furthermore, we also mentioned potential targeted therapies, challenges, and progress in clinical trials, as well as new biomarkers and therapeutic targets. Finally, other relevant cell interactions in neuropathic pain and the role of glial cells in other neuropathic pain conditions have been discussed. This review serves as a comprehensive resource for further investigations into the microglia-astrocyte interaction and the detailed mechanisms of neuropathic pain after SCI, with the aim of improving therapeutic efficacy.