Abstract:Abstract:?Neuropathic pain (NP) is a refractory chronic pain condition, and its pathogenesis is closely associated with the activation of spinal microglia and astrocytes. With the advancement of research on the microbiota-gut-brain axis, the gut microbiota have been demonstrated to modulate central and peripheral neuroinflammation through their metabolites and immune regulatory pathways, thereby influencing the development and maintenance of NP. Furthermore, the gut microbiota exhibit promising therapeutic potential by alleviating NP through the regulation of microglial and astrocytic activation, as well as the TLR4/NF-κB signaling pathway. However, current research on the "gut-brain axis" predominantly focuses on the brain. While these studies have confirmed the role of the gut microbiota in influencing pain via neuroinflammation, they have largely overlooked spinal cord glial cells, which serve as the primary regulatory center for pain, thereby limiting a comprehensive understanding of the underlying mechanisms. This review focuses on how the gut microbiota and their metabolites, via the circulatory system, directly regulate spinal glial cell activity, which in turn modulates neuronal excitability through the release of inflammatory mediators, revealing their pivotal role in NP initiation and chronification. This novel perspective not only deepens the understanding of NP mechanisms but also provides a crucial theoretical basis for developing innovative analgesic strategies that target the microbiota to intervene directly at the primary pain center.
