Mechanism and treatment for chronic pain : geretic engineering

慢性疼痛的机制和治疗：老年工程

• 批准号: 10557139
• 负责人: UCHIDA Ichiro
• 金额: $ 7.94万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10557139/
• 关键词: Genetic engineering; chronic pain; mechanism; MNDA receptor; subunit; electrophysiology; xeropus; adeno virus; 慢性痛; 神経因性; 遺伝子治療; 疼痛モデル; アデノウイルス; マウス; NMDA受容体; アデノウィルス

The aim of this project was to explore the mechanism of chronic pain (neuropathic pain) and establish its treatment using the genetic engineering approach. As one of target receptors involved in the mechanism of chronic pain, we have focused on the NMDA receptors in the central nervous system. First, we examined the interactions of NMDA receptor and the neuropathic agents such as local anesthetics, general anesthetics using the recombinant receptor technique. Then we tried to examine the role of NMDA receptor in the neuropathic pain model rat using the anti-sense strategy by adenovirus vectors. However, the effectiveness of the receptor knock down technique by adenovirus was poor to affect in vivo the neuropathic pain of the rat model and this methods have resulted in not getting reproducible data. Therefore in this reports we addressed to the specific interactions of the neuropathic drugs and central nervous receptors related to the pain sensation such as NMDA, 5HT3 and GABA_A receptors.

本项目的目的是探索慢性疼痛（神经病理性疼痛）的机制，并利用基因工程方法建立其治疗方法。NMDA受体作为参与慢性疼痛发生机制的靶受体之一，近年来对中枢神经系统NMDA受体的研究越来越多。首先，我们利用重组受体技术研究了NMDA受体与局麻药、全麻药等神经病理性药物的相互作用。然后，我们尝试用腺病毒介导的反义策略，研究NMDA受体在神经病理性疼痛模型大鼠中的作用。然而，通过腺病毒的受体敲低技术在体内影响大鼠模型的神经病理性疼痛的有效性较差，并且该方法导致不能获得可重复的数据。因此，本研究主要探讨神经病药物与与痛觉相关的中枢神经受体如NMDA、5-HT_3和GABA_A受体的特异性相互作用。

项目成果

Suzuki T, Koyama H, Sugimoto M, Uchida I, Nashimo T: "The diverse actions of volatile and gaseous anesthetics on human cloned 5-HT3 receptors in Xenopus oocytes."Anesthesiology. 93. (2000)

Suzuki T、Koyama H、Sugimoto M、Uchida I、Nashimo T：“挥发性麻醉剂和气体麻醉剂对非洲爪蟾卵母细胞中人类克隆 5-HT3 受体的多种作用。”麻醉学。

Sugimoto M, Uchida I, Mashimo M, Matsuoka N, Yamazaki S, Hatano K, Ikeda F.: "The role of GABA_A receptors in the antibiotic-induced convulsion."Soc. Neurosci. Abstr.. 26. 855 (2000)

Sugimoto M、Uchida I、Mashimo M、Matsuoka N、Yamazaki S、Hatano K、Ikeda F.：“GABA_A 受体在抗生素引起的惊厥中的作用。”Soc。

Koyama H, Sugimoto M, Fukami S, Uchida I & Mashimo T: "Gas anesthetics, nitrous oxide (N2O) and xenon (Xe) had no effects on recombinant GABAA receptors expressing in Xenopus oocyte."Anesth. Analg.. 90. S439 (2000)

小山 H、杉本 M、深见 S、内田 I

Sugimoto et al: "The α and γ subunit dependent effects of local anesthetics on GABAA receptors"Eur.J.Pharmacol. 401. 329-337 (2000)

Sugimoto 等人：“局部麻醉剂对 GABAA 受体的 α 和 γ 亚基依赖性作用”Eur.J.Pharmacol. 401. 329-337 (2000)

Suzuki T et al: "The diverse effects of volatile and gaseous anesthetics on human cloned PHT3 receptors"Anesthesiology. 93. A141 (2000)

Suzuki T 等人：“挥发性麻醉剂和气体麻醉剂对人类克隆 PHT3 受体的多种影响”麻醉学。