Investigation of the network of analgesic mechanisms in the spinal cord

脊髓镇痛机制网络的研究

基本信息

批准号：
12671453
负责人：
NISHIYAMA Tomoki
金额：
$ 2.11万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671453/
关键词：
Spinal cord Analgesia Rat NMDA receptor AMPA receptor α_2 receptor GABA_A receptor acetylcholine receptor セロトニン受容体ミダゾラムクロニジン脊随 GABA受容体グルタミン酸受容体セトロニン受容体 α_2受容体

项目摘要

Splague-Dawley rats were implanted with lumbar intrathecal catheters. Midazolam (GABA_A receptor agonist), AP-5 (NMDA receptor antagonist), YM872 (AMPA receptor antagonist), bupivacaine (local anesthetic), clonidine (α_2 receptor agonist), serotonin (serotonin receptor agonist), and epibatidine (acetyocholine receptor agonist) were examined of their analgesic effects by intrathecai administration using the Tail flick test and Formalin test. All the agents showed dose dependent analgesic effects on both tail flick test and Formalin test and 50% effective doses (ED_<50>) were obtained. The interaction of two agents was examined with the combination of 1/2ED_<50>, 1/4ED_<50>, 1/8ED_<50>, or 1/16ED_<50> of each agent using an isobolographic analysis. Eight rats were used in each dose. Bupivacaine + AP-5, or clonidine, epibatidine + YM872 or clonidine, and midazolam + serotonin, in the Tail flick test, and epibatidine + serotonin, or clonidine in the phase 1 of the Formalin test showed additive effects. Bupivacaine + serotonin, and epibatidine + midazolam in the phase 2 of the Formalin test were antagonistic. No interaction was seen in the phase 2 of the Formalin test with serotonin + midazolam, and epibatidine + serotonin or clonidine. Other combinations in both tests showed significant synergistic analgesic effects.

将腰dawley大鼠植入腰椎鞘内导管。咪达唑仑（GABA_A受体激动剂），AP-5（NMDA受体激动剂），YM872（AMPA受体受体激动剂），布比卡因（局部麻醉）（α___2受体激动剂），羟色胺受体受体（呼吸蛋白）和epibibide Oricochin（actibibed Oneristin）（α_2受体激动剂） Intrathecai给药的镇痛作用使用尾部轻弹测试和福尔马林测试。所有在尾部轻弹测试和福尔马林测试中均显示了剂量依赖性镇痛作用，并获得了50％有效剂量（ED_ <50>）。通过使用同胞分析的1/2ED_ <50>，1/4ED_ <50>，1/8ED_ <50>或1/16ED_ <50>的1/2ED_ <50>，1/4ED_ <50>，1/4ED_ <50>，1/4ED_ <50>，1/4ED_ <50>的相互作用进行了检查。每个剂量中使用八只大鼠。在尾弹片测试中，布比卡因 + AP-5，或可乐定，Epibatidine + YM872或可乐定和咪达唑仑 + 5-羟色胺，以及Epibatidine + 5-羟色胺 + 5-羟色胺或福尔马林测试期1期中的Clonidine显示了附加效果。在福尔马林测试的第2阶段中，布比卡因 + 5-羟色胺和Epibatidine +咪达唑仑是对立的。在福尔马林测试的第2阶段与5-羟色胺 +咪达唑仑，Epibatidine + 5-羟色胺或可乐定相互作用。两种测试中的其他组合都显示出显着的协同镇痛作用。