Fibroblast Growth Factor 8 Suppresses Neurotoxic Astrocytes and Alleviates Neuropathic Pain via Spinal FGFR3 Signaling.

ABSTRACT: Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3⁺, A1-like) and S100 calcium-binding protein A10 (S100A10⁺, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microg

SUBMITTER: Liu H 

PROVIDER: S-EPMC12698887 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature