Gintonin prevents paclitaxel-induced neuropathic pain via spinal LPA₃ receptors and oligodendrocyte precursor cells in mice

Background Chemotherapy-induced peripheral neuropathy (CIPN) remains a major clinical challenge with limited treatment options. Gintonin, a glycolipoprotein complex derived from Panax ginseng Meyer , acts as a ligand for lysophosphatidic acid (LPA) receptors and has been reported to exert neuroprotective effects. This study investigated gintonin's actions in paclitaxel-induced neuropathic pain (8 mg/kg, i.p.), focusing on a previously unreported LPA₃–OPC mechanism. Methods Gintonin (50–200 mg/kg, p.o.) was repeatedly administered in a paclitaxel-induced neuropathic pain model. Mechanical and cold allodynia were assessed, and spinal tissues were analyzed for LPA receptor expression. Receptor-specific siRNAs were intrathecally delivered to identify the subtype involved. Immunofluorescence and Cy5.5-labeled gintonin were used to examine LPA₃ receptor localization in NG2⁺ oligodendrocyte precursor cells (OPCs). Results Gintonin attenuated paclitaxel-induced mechanical and cold allodynia, with the greatest effects observed at 100 and 200 mg/kg, and upregulated spinal gene expression of LPA₁ and LPA₃, but not LPA₂ receptor. LPA ₃ -specific siRNA abolished its analgesic effect, confirming LPA₃ receptor dependence. Gintonin also preserved NG2⁺ OPCs, with immunofluorescence and Cy5.5-labeled gintonin demonstrating co-localization with LPA₃ receptors. Conclusion These findings suggest that gintonin prevents paclitaxel-induced neuropathic pain through LPA₃ receptor–mediated regulation of spinal OPCs.