Decoding of the Role of TREM2 in Neuropathic Pain: Molecular Pathway and Neuroinflammatory Mechanism

Neuropathic pain is a debilitating condition characterized by chronic pain that is often refractory to conventional treatments. Increasing evidence suggests that microglia, the resident immune cells of the central nervous system, play a crucial role in modulating pain pathways through neuroinflammatory mechanisms. The Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), in conjunction with DNAX-activating protein 12 (DAP12), regulates microglial activation and immune responses, thereby influencing neuropathic pain progression. This review explores the molecular mechanisms by which TREM2 contributes to pain modulation, focusing on its role in microglial activation, cytokine release, oxidative stress, and neuronal sensitization. Furthermore, we discuss the therapeutic potential of targeting TREM2 signaling for neuropathic pain management. Understanding the interplay between TREM2 and neuroinflammation offer novel insights into developing targeted interventions for chronic pain conditions.