权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The role of SNS Na channel in chronie pain

SNS Na通道在慢性疼痛中的作用

基本信息

批准号：
11671495
负责人：
UCHIDA Ichiro
金额：
$ 2.43万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

The aim of this project was to explore the role of SNS Na channel in the mechanism of chronic pain (neuropathic pain). However the expression of SNS Na+ channel in the oocyte system has not been achieved to the level to collect the data for the assessment using the electrophysiological method. Therefore we have focused on the NMDA receptors and 5-HT3 receptor in the central nervous system as one of target receptors involved in the mechanism of chronic pain,. First, we examined the interactions of NMDA receptor and the neuropathic agents such as local anesthetics, using the recombinant receptor technique including the site-directed mutagenesis. Local anesthetics inhibited the NMDA receptor function in dose-dependent manners. The rank order in the potencies of local anesthetics to the NMDA receptor were different from that to voltage-sensitive Na channel. The site of action for procaine was related to that for ketamine and Mg+. Then we tried to examine the effect of general anesthetics such N2O and xenon which posses the analgesic actions on the 5-HT3 receptor. These gas anesthetics dose-dependently inhibited the 5-HT3 receptor. In contrast volatile anesthetics such as isoflurane and halothane except sevoflurane potentiated the 5-HT3 receptor function. In this investigation we addressed to the specific interactions of the neuropathic drugs and central nervous receptors related to the pain sensation such as NMDA and 5HT3 receptors.

本项目旨在探讨SNS Na通道在慢性疼痛（神经性疼痛）发生机制中的作用。然而，在卵母细胞系统中，SNS Na+通道的表达尚未达到电生理方法评估所需数据的水平。因此，我们关注中枢神经系统的NMDA受体和5-HT3受体作为参与慢性疼痛机制的靶受体之一。首先，我们研究了NMDA受体与神经病变药物（如局部麻醉剂）的相互作用，使用重组受体技术，包括位点定向诱变。局麻药对NMDA受体功能的抑制呈剂量依赖性。局麻药对NMDA受体的作用顺序与对电压敏感的Na通道的作用顺序不同。普鲁卡因的作用位点与氯胺酮和镁离子的作用位点相关。然后，我们试图研究N2O和氙气等具有镇痛作用的全身麻醉剂对5-HT3受体的影响。这些气体麻醉剂剂量依赖性地抑制5-HT3受体。相反，除七氟烷外，异氟烷和氟烷等挥发性麻醉剂可增强5-HT3受体的功能。在本研究中，我们探讨了神经性病变药物与中枢神经痛觉相关受体（如NMDA和5HT3受体）的具体相互作用。