羌活水提液通过TRPV1调节神经病理性疼痛镇痛机制研究

Water Extract of Notopterygium Incisum Alleviates Neuropathic Pain by Regulating TRPV1

目的探索羌活水提液(Water extract of notopterygium incisum,WN)对神经病理性疼痛的作用及分子生物学机制。方法疼痛行为实验检测WN灌胃对急性疼痛模型小鼠和慢性缩窄性损伤(Chronic constriction injury,CCI)引起的神经病理性疼痛模型小鼠热痛觉过敏和机械痛觉过敏的影响。免疫组织化学、qPCR法检测WN灌胃对小鼠DRG神经元TRPV1表达的影响。钙成像法检测WN灌胃后CCI模型小鼠DRG神经元对TRPV1激动剂辣椒素钙内流的影响。结果WN灌胃后,可显著减轻急性疼痛模型小鼠和CCI模型小鼠的热痛觉过敏和机械痛觉过敏(P<0.001)。与模型组比较,WN组DRG神经元TRPV1蛋白及mRNA表达均受到显著抑制(P<0.05),DRG神经元对TRPV1激动剂辣椒素的反应显著减弱(P<0.001)。结论WN可能通过调节TRPV1来减轻CCI引起的疼痛,为中药镇痛的分子生物学机制提供新的思路和基础。

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.