中脑导水管周围灰质OrexinA及其受体OX1R通过大麻素受体1参与针刺缓解内脏痛敏的机制研究

中枢敏化是肠易激综合征（IBS）内脏痛敏发生过程中的关键因素，针刺主要通过激活下行抑制系统抑制内脏痛敏。研究显示OrexinA是一种在脊髓及脊髓上水平疼痛调控中具有重要作用的神经肽，而导水管周围灰质（PAG，下行抑制系统关键环节）是OrexinA发挥脊髓上水平抗伤害作用的重要脑区。结合申请人前期工作基础即OrexinA通过其受体OX1R参与针刺对于下行抑制系统的激活效应，本研究拟采用行为学、神经药理学、分子生物学及神经电生理等技术，开展如下研究：1)证实电针通过调控中脑vlPAG的OrexinA及其受体发挥抗中枢敏化效应；2)阐明中脑PAG的OrexinA及OX1R通过激活下游大麻素受体（CB）1参与电针缓解内脏痛敏效应；3)深入阐释OX1R-CB1通路引起的突触前抑制是OrexinA参与电针镇痛的关键分子机制，以期为临床针刺调控下行抑制系统从而抑制中枢敏化提供理论基础和科学依据。

Central sensitization is a key factor in the development of visceral hypersensitivity of irritable bowel syndrome (IBS). Acupuncture mainly activates descending inhibitory pathway to relieve visceral hypersensitivity. Studies show that orexinA is a pivotal peptide that plays an anti-nociceptive role in pain regulation both at spinal and supra-spinal levels, and periaqueductal gray matter (PAG, the major section of descending inhibitory pathway) is the key region where orexinA exerts the anti-nociceptive effect on. Our previous research found that orexinA is involved in acupuncture-induced analgesia through its receptor OX1R to activate descending inhibitory pathway. Thus, the present study is employing behavior tests, neuropharmacological, molecular biological and electrophysiological measures etc, 1) to verify that acupuncture produces the anti-central sensitization effect through regulating PAG orexinA and OX1R; 2) to illuminate that orexinA and OX1R participate in acupuncture-induced analgesia in visceral hypersensitivity through activating CB1; and 3) to further explore that presynaptic inhibition produced by OX1R-CB1 activation is the molecular mechanism of the orexinA involvement in acupuncture-induced analgesia. Results of the study can be expected to provide theoretical and scientific evidence in acupuncture regulation of descending inhibitory pathway to inhibit central sensitization.