Abstract
Neuropathic pain (NPP) is intolerable, persistent, and specific type of long-term pain. It is considered to be a direct consequence of pathological changes affecting the somatosensory system and can be debilitating for affected patients. Despite recent progress and growing interest in understanding the pathogenesis of the disease, NPP still presents a major diagnostic and therapeutic challenge. High mobility group box 1 (HMGB1) mediates inflammatory and immune reactions in nervous system and emerging evidence reveals that HMGB1 plays an essential role in neuroinflammation through receptors such as Toll-like receptors (TLR), receptor for advanced glycation end products (RAGE), C-X-X motif chemokines receptor 4 (CXCR4), and N-methyl-D-aspartate (NMDA) receptor. In this review, we present evidence from studies that address the role of HMGB1 in NPP. First, we review studies aimed at determining the role of HMGB1 in NPP and discuss the possible mechanisms underlying HMGB1-mediated NPP progression where receptors for HMGB1 are involved. Then we review studies that address HMGB1 as a potential therapeutic target for NPP.
Highlights
Pain is a type of physical experience defined as an unpleasant sensory and mental problem resulting from actual or potential tissue damage, or something that makes people uncomfortable (International Association for the Study of Pain) [1]
These data suggest that the High mobility group box 1 (HMGB1)/TLR4 signaling pathway plays a central role in the occurrence and development of neuropathic pain (NPP), and a therapy targeting HMGB1/Toll-like receptors (TLR)-4 might be a novel strategy for the treatment of NPP
HMGB1 plays an essential role in the pathogenesis of a large number of inflammatory conditions and has been identified as a mediator of neuroinflammation
Summary
Pain is a type of physical experience defined as an unpleasant sensory and mental problem resulting from actual or potential tissue damage, or something that makes people uncomfortable (International Association for the Study of Pain) [1]. HMGB1 acts as a prototypical damage-associated molecular pattern molecule (DAMP) and promotes inflammasome activation [32] This particular DAMP cooperates with other factors such as chemokines, growth factors, and cytokines and orchestrates the inflammatory and immune response [38]. HMGB1 released by immune cells is highly proinflammatory via cooperation with several definitive receptors that are involved in the inflammatory reaction These receptors include the receptor for advanced glycation end products (RAGE) [41, 42], Tolllike receptors (TLR-2, TLR-4, and TLR-9) [43,44,45], integrin [46], SNCA/α-Synuclein filaments [47], CD24 [48], and NMDA receptor [49].
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