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The mechanism of 5-HT receptor agonists for inhibitory effect in neuropathic pain

5-HT受体激动剂抑制神经病理性疼痛的机制

基本信息

批准号：
12671451
负责人：
OBATA Hideaki
金额：
$ 1.09万
依托单位：
Gunma University
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 2001
项目状态：
已结题

项目摘要

Several lines of evidence demonstrated that bulbospinal serotonergic (5-HT) systems mediate suppression of nociceptive input to spinal dorsal horn. Intrathecally administered 5-HT has antinociceptive effects in acute pain models in animals. Autoradiographic studies have revealed that the presence of several 5-HT receptors in the spinal cord. Although some controversy persists, 5-HT_<1A>, 5-HT_<1B>, 5-HT_2, 5-HT_3 receptor subtypes have been reported to contribute to the antinociceptive action of 5-HT in the spinal cord. However, whether activation of these spinal 5-HT receptor subtypes inhibits neuropathic pain is unknown. It has been reported that tight ligation of spinal nerves L5 and L6 lead to allodynia. We used various agonists and antagonists to compare antiallodynic actions at each spinal 5-HT receptor subtypes in this rat model of allodynia, and found that only intrathecally administered 5-HT_2 receptor agonists produced antiallodynic action (Pain 2001 ; 90 : 173-179). Further, we examined the mechanisms of antiallodynic effect of intrathecally administered 5-HT_2 receptor agonists. It has been reported that 5-HT regulates several neurotransmitters, such as acetylcholine, noradrenaline, GABA, or adenosine, in central nervous system. Therefore, we investigated the possible involvement of other associated spinal receptor systems with respect to the antiallodynic action of a 5-HT_2 receptors agonist. From these experiments, we found that muscarinic receptor antagonists reversed the antiallodynic effects of intrathecally administered 5-HT_2 receptor agonists (Brain Res, In Press). Acetylcholine release and muscarinic receptor activation in the spinal cord appears to be, at least in part, involved in the antiallodynic action of an intrathecally administered 5-HT_2 receptor agonists.

一些证据表明，球脊髓5-羟色胺能（5-HT）系统介导对脊髓背角伤害性输入的抑制。鞘内注射5-HT在动物急性疼痛模型中具有抗伤害性作用。放射自显影研究表明，脊髓中存在几种5-HT受体。尽管目前还存在一些争议，但已有报道5-HT_<1A>、5-HT_<1B>、5-HT_2、5-HT_3受体亚型参与了脊髓5-HT的抗伤害作用。然而，这些脊髓5-HT受体亚型的激活是否抑制神经性疼痛尚不清楚。据报道，L5和L 6脊神经的紧密结扎导致异常性疼痛。我们使用各种激动剂和拮抗剂来比较在该大鼠异常性疼痛模型中每种脊髓5-HT受体亚型的抗异常性疼痛作用，并且发现仅鞘内施用5-HT_2受体激动剂产生抗异常性疼痛作用（Pain 2001 ; 90：173-179）。进一步探讨了鞘内注射5-HT_2受体激动剂的抗异常性疼痛作用机制。据报道，5-HT在中枢神经系统中调节多种神经递质，如乙酰胆碱、去甲肾上腺素、GABA或腺苷。因此，我们研究了其他相关的脊髓受体系统与5-HT_2受体激动剂的抗异常性疼痛作用的可能参与。从这些实验中，我们发现毒蕈碱受体拮抗剂逆转鞘内给药的5-HT_2受体激动剂的抗异常性疼痛作用（Brain Res，In Press）。脊髓乙酰胆碱释放和毒蕈碱受体激活似乎至少部分参与鞘内注射5-HT_2受体激动剂的抗异常性疼痛作用。