Acupuncture mitigates sciatic neuropathic pain in lumbar disc herniation via inhibiting spinal CXCL12/CXCR4-driven glial activation and neuroinflammation.

Lumbar disc herniation (LDH) is a prevalent degenerative spinal disorder causing chronic low back pain and sciatica through persistent neuroinflammation and central sensitization. Increasing evidence implicates the CXCL12/CXCR4 signaling axis in these processes, yet its modulation by acupuncture remains unclear. To explore this mechanism, a rat model of LDH was established by autologous nucleus pulposus implantation adjacent to the L5 dorsal root ganglion, and behavioral hypersensitivity was assessed using von Frey and plantar tests. LDH induced marked mechanical and thermal hyperalgesia accompanied by upregulation of CXCL12 and CXCR4 in the spinal dorsal horn. CXCL12 localized mainly to neurons and microglia, while CXCR4 was expressed in neurons, astrocytes, and microglia. Pharmacological blockade of CXCR4 with AMD3100 alleviated hypersensitivity and reduced neuronal and glial activation. Acupuncture similarly increased withdrawal thresholds, inhibited c-Fos, GFAP, and Iba-1 expression, and suppressed TNF-α, IL-1β, and IL-6 levels, whereas exogenous CXCL12 reversed these effects. Acupuncture also inhibited ERK1/2 and NF-κB phosphorylation, and selective inhibition of these pathways with PD98059 or PDTC reproduced its analgesic effects. These findings identify the CXCL12/CXCR4-ERK/NF-κB axis as a critical mediator of LDH-induced neuroinflammation and demonstrate that acupuncture mitigates neuropathic pain by suppressing this signaling pathway and glial activation.