Abstract: OBJECTIVE  To explore the effect of water extract of notopterygium incisum (WN) on neuropathic pain and its molecular biological mechanism.METHODS  Pain behavior test to detect the effects of WN on thermal hyperalgesia and mechanical hyperalgesia in acute pain and chronic constriction injury (CCI) induced neuropathic pain model. Immunohistochemistry and qPCR were used to detect the expression of TRPV1. Calcium imaging was used to detect calcium influx of capsaicin (TRPV1 agonist) in CCI mice after oral administration of WN.RESULTS  WN significantly reduced the thermal hyperalgesia and mechanical hyperalgesia in acute pain model and CCI model (P < 0.001). The expression of TRPV1 in protein level and mRNA level in DRG neurons were significantly inhibited by administration of WN (P < 0.05). The response of DRG neurons to capsaicin was significantly inhibited by the treatment of WN (P < 0.001).CONCLUSION  WN alleviated CCI-induced mechanical allodynia and thermal hypersensitivity via modulating TRPV1. Our results revealed a new molecular biological mechanism of analgesia effect to traditional Chinese medicine.