[miR-143-3p alleviates neuropathic pain in mice with spared nerve injury by targeting the KRAS/RalA pathway and inhibiting astrocyte activation].

objectivesTo investigate the therapeutic effect of microRNA (miR-143-3p) on neuropathic pain in mice and clarify its target gene and molecular mechanism.

methodsSpared nerve injury (SNI) models were established in 8-week-old male C57BL/6J mice, with sham-operated mice as the control group (

resultsmiR-143-3p agomir significantly increased mechanical withdrawal thresholds of SNI mice, and the effect lasted nearly 3 weeks. KRAS was identified as a direct target of miR-143-3p. In SNI mouse models, miR-143-3p significantly inhibited KRAS expression, RalA/TBK1/NF-κB signaling pathway activation, and astrocyte activation, and upregulated the levels of IL-6, IL-1β, and TNF-α. The KRAS agonist KRA-533 significantly reversed the analgesic effect of miR-143-3p and its inhibitory effects on downstream pathway activation, astrocyte activation, and neuroinflammation. In C8-D1A cells, overexpression of miR-143-3p effectively suppressed LPS-induced noncanonical Ras pathway activation and inhibited cell proliferation and inflammatory response, which were reversed by treatment with KRA-533.

conclusionsmiR-143-3p overexpression alleviates neuropathic pain in mice by targeting KRAS to regulate the noncanonical Ras pathway and inhibiting astrocyte activation and neuroinflammation, suggesting a new strategy for clinical treatment of SNI.