Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats
Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats
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DOI：
10.1016/s0304-3959(99)00307-3
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发表时间：
2000-05-01
期刊：
影响因子：
7.4
通讯作者：
Eschalier, A
中科院分区：
文献类型：
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作者：
Bardin, L;Lavarenne, J;Eschalier, A
本研究旨在通过机械疼痛测试研究脊髓 5-HT 受体的哪些亚型参与 5-MT 诱导的镇痛作用。大鼠鞘内注射血清素和各种 5-HT 受体亚型（5-HT(1A)、5-HT(1B)、5-HT(2A)、5-HT(2C)、5-HT(3) 和 5-HT(4)）选择性拮抗剂或激动剂。它。根据爪压测试，注射 5-HT（1 微克）产生显着的镇痛作用。用5-HT(2C)受体拮抗剂美舒麦角(mesulegine)(1和10μg)和5-HT(3)受体拮抗剂托烷司琼(1和10μg)预处理完全逆转了5-HT诱导的镇痛作用。此外，在10μg的剂量下，5-HT(2A)受体拮抗剂酮舍林和5-HT(1B)受体拮抗剂喷布洛尔均不减弱5-HT诱导的镇痛作用，但5-HT(1A)受体拮抗剂WAY 100635和5-HT(4)受体拮抗剂GR113808均不减弱。此外，还有一个 i.t.注射5-HT(3) 激动剂mCPBG 诱导显着的镇痛作用，而5-HT(2) 激动剂DOI 则不产生镇痛作用。这些结果表明，尽管由于激动剂或拮抗剂的作用存在一些差异，脊髓血清素能 5-HT(3) 受体参与的精确程度仍有待阐明，但这些受体似乎在 5-HT 针对机械急性伤害性刺激的镇痛作用中发挥作用。由于观察到所用激动剂和拮抗剂的作用之间存在差异，因此 5-HT(2C) 的参与更值得怀疑。 5-HT(1A) 和 5-HT(4) 受体似乎不参与其中。此外，脊髓血清素受体之间可能存在功能性相互作用。 (C) 2000 年国际疼痛研究协会。由 Elsevier Science B.V. 出版。保留所有权利。
The present study was designed to investigate which subtypes of spinal 5-HT receptors are involved in 5-MT-induced antinociception using the mechanical pain test. Serotonin and various selective antagonists or agonists for 5-HT receptor subtypes (5-HT(1A), 5-HT(1B), 5-HT(2A), 5-HT(2C), 5-HT(3) and 5-HT(4)) were administered intrathecally (i.t.) in rats. The i.t. injection of 5-HT (1 mu g) produced significant antinociceptive effects using the paw pressure test. Pretreatment with the 5-HT(2C) receptor antagonist mesulergine (1 and 10 mu g) and the 5-HT(3) receptor antagonist tropisetron (1 and 10 mu g) reversed totally the antinociception induced by 5-HT. Furthermore, at a dose of 10 mu g, both the 5-HT(2A) receptor antagonist ketanserin and the 5-HT(1B) receptor antagonist penbutolol, but neither the 5-HT(1A) receptor antagonist WAY 100635 nor the 5-HT(4) receptor antagonist GR113808, attenuated the antinociceptive effect induced by 5-HT. In addition, an i.t. injection of the 5-HT(3) agonist mCPBG induced significant antinociceptive effects whereas the 5-HT(2) agonist DOI did not produce analgesia. These results suggest that although the precise degree of the involvement of spinal serotonergic 5-HT(3) receptors remains to be elucidated due to some differences in the effect of agonists or antagonists, these receptors seem to play a role in the antinociceptive effect of 5-HT against a mechanical acute noxious stimulus. The involvement of 5-HT(2C) is more questionable due to the observed discrepancies between the effects of the used agonist and antagonist. 5-HT(1A) and 5-HT(4) receptors do not seem to be involved. In addition, a possible functional interaction between spinal serotonergic receptors may exist. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.