Lidocaine alleviates diabetic neuropathic pain by inhibiting spinal astrocyte activation through modulation of the CXCL13/CXCR5 axis.

This study aimed to investigate the analgesic effects of lidocaine (Lido) on diabetic neuropathic pain (DNP), a common complication of diabetes, and to elucidate the underlying mechanism. A DNP mouse model was established by a single streptozotocin injection at 200 mg/kg. Two weeks later, mice received intraperitoneal infusion with 2% Lido for 7 consecutive days. The analgesic effect of Lido was assessed by pain behavioral tests. Astrocyte activation, pro-inflammatory cytokine levels, and CXCL13 and CXCR5 expression were examined in mechanistic studies. Lido significantly improved mechanical allodynia and thermal hyperalgesia in DNP mice. Lido reduced spinal astrocyte activation and pro-inflammatory cytokine levels in DNP mice. It also inhibited CXCL13 and CXCR5 expression, with their upregulation diminishing Lido's analgesic effects. Lido alleviates DNP by inhibiting spinal astrocyte activation via modulation of the CXCL13/CXCR5 axis.