从Sigma-1受体介导的痛觉传递研究艾灸缓解慢性内脏痛敏的中枢机制

Moxibustion has shown its effects in relieving abdominal pain in irritable bowel syndrome (IBS) patients and IBS rat models, but its mechanisms are largely unknown. Based on the results of our preliminary studies, the hypothesis "Sigma-1 receptor may be involved in chronic visceral hyperalgesia and moxibustion analgesia"is proposed. In this study, we determine the role of spinal Sigma-1 receptor in analgesic effect of warming moxibustion on chronic visceral hyperalgesia in IBS-like rat model induced by colorectal distention. The experiments in vivo and in vitro will be involved in the study. The scoring system of abdominal withdrawal reflex was used to evaluate visceral pain for behavioral assessment. The mRNA and protein of Sigma-1 receptor, dynorphin-Kappa receptor and Glutimate-NMDA receptor in spinal dorsal horn will be observed by immune technology an methods. Intrathecal treatment with Sigma-1 receptor antagonists or agonists also be applied to study the effct of Sigma-1 receptor on dynorphin-Kappa sysytem and Glutimate-NMDA system.The finding will support the clinical use of moxibustion in treatment of visceral pain and may initiate a discussion on the Sigma-1 receptor mechanisms of moxibustion analgesia.

在前期研究的基础上，本项目围绕"Sigma-1受体是IBS慢性内脏痛敏及艾灸对其调节机制中的关键性分子"的工作假说，率先从Sigma-1受体调节角度探讨艾灸缓解慢性内脏痛敏的中枢机制。以"合募配穴"中医针灸理论为指导，以温和灸为干预手段，选择IBS慢性内脏痛敏大鼠模型为研究对象，采用行为学与形态学、在体实验与离体实验相结合，应用免疫电镜、免疫荧光及激光扫描共聚焦等技术与方法观察Sigma-1受体在模型大鼠脊髓背角的表达及温和灸天枢、上巨虚穴对其的影响；拮抗或激动Sigma-1受体对内源性镇痛系统（强啡肽-Kappa受体）及致痛系统（谷氨酸-NMDA受体）的影响，深入探讨艾灸缓解慢性内脏痛敏的神经生物学机制，以期为临床艾灸效穴治疗疼痛性疾病提供科学的实验依据与理论基础。

慢性内脏痛的研究表明，其形成和发展与脊髓的内源性阿片肽系统和谷氨酸递质受体系统有着密切的联系。近年研究提示，Sigma-1 受体（sigmal -1 receptor, sigma-1R）在痛觉信号转导和内脏痛敏中起重要调节作用。本项目围绕“Sigma-1 R是IBS 慢性内脏痛敏及艾灸对其调节机制中的关键性分子”的工作假说，从Sigma-1 R角度探讨艾灸缓解慢性内脏痛敏的中枢机制。选择IBS 慢性内脏痛敏大鼠模型为研究对象，观察Sigma-1R在模型大鼠脊髓背角的表达及温和灸天枢、上巨虚穴对其的影响；拮抗Sigma-1 R对内源性镇痛系统（强啡肽-Kappa 受体）及致痛系统（谷氨酸-NMDA 受体）的影响。研究发现:1.脊髓背角Sigma-1R在IBS大鼠慢性内脏痛敏机制中发挥重要作用。2.抑制脊髓水平Sigma-1R，进而促进强啡肽-Kappa 受体系统，抑制谷氨酸-NMDA 受体系统是艾灸缓解IBS慢性内脏痛敏的中枢机制之一。