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脊髓5-HT3A受体对BmK I诱发的大鼠炎性痛的影响

傅晋, 焦云露, 李正威, 吉永华^*

上海大学神经药理学与毒理学实验室，上海 200444

摘要

通过皮下注射BmK I能够建立新型大鼠疼痛模型。五羟色胺(5-HT)受体参与调控动物疼痛相关行为。本文旨在研究5-HT3受体调控BmK I诱发疼的潜在机制。应用动物行为学、RT-PCR、蛋白印迹等技术手段进行相关研究，得到如下结果：足底注射BmK I (10 μg)可诱导脊髓L4~L5段5-HT3A受体蛋白与mRNA表达增多，鞘内注射5-HT3A受体特异性拮抗剂ondansetron减少了自发痛反应，减弱了BmK I诱发的单侧热敏和双侧机械超敏；足底注射BmK I可能诱发了小胶质细胞的激活，且该效应能够被鞘内预注射ondansetron所逆转。脊髓L4~L5段5-HT3A受体主要表达于神经元，而不表达于小胶质细胞；另外，鞘内预注射ondansetron能够降低趋化因子CX3CL1与趋化因子受体CX3CR1在脊髓L4~L5段的表达水平。以上结果提示，5-HT3A受体信号通路与小胶质细胞激活共同参与BmK I诱发疼的起始与维持。神经元5-HT3A受体可能间接地通过CX3CL1参与与小胶质细胞间的“串话”，CX3CL1参与调控BmK I诱导的痛觉超敏与敏化。

关键词： BmK I 诱发痛; 5-HT3A受体; 小胶质细胞; 痛觉超敏与敏化

分类号：R338.8

Spinal 5-HT3AR contributes to BmK I-induced inflammatory pain in rats

FU Jin, JIAO Yun-Lu, LI Zheng-Wei, JI Yong-Hua^*

Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China

Abstract

Subcutaneous injection of BmK I could be adopted to well establish a novel pain model. Moreover, 5-hydroxytryptamine (serotonin, 5-HT) receptor is involved in regulating animal pain-related behaviors. However, the underlying mechanism of 5-HT3R on BmK I-induced pain remains unclear. Animal behavioral testing, RT-PCR and Western blotting were used to yield the following results: first, intraplantar (i.pl.) injection of BmK I (10 μg) induced elevated mRNA and protein levels of 5-HT3AR in bilateral L4–L5 spinal cord; Second, intrathecal (i.t.) injection of ondansetron (a specific antagonist of 5-HT3AR) reduced spontaneous pain responses, attenuated unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I; Microglia could be activated by BmK I (i.pl.) in both sides of L4–L5 spinal cord, and this effect was reversed by intrathecal pre-treatment with 5-HT3AR antagonist. Meanwhile, the 5-HT3AR in L4–L5 spinal cord was almost co-localized with NeuN (a marker of nerve cell), but not co-expressed with Iba-1 (a marker of microglia). Finally, the expression level of CX3CL1 and CX3CR1 was reduced by intrathecal pre-treatment with ondansetron. Our results indicate that both 5-HT3AR signaling pathway and microglia are activated in the process of induction and maintenance of BmK I-induced pain nociception. Meanwhile, our results suggest that the neuronal 5-HT3AR may communicate with microglia indirectly via CX3CL1 which is involved in regulating the BmK I-induced hyperalgesia and sensitization.

Key words: BmK I-induced pain; 5-HT3AR; microglia; hyperalgesia and sensitization

收稿日期：2015-02-28　　录用日期：2015-06-01

通讯作者：吉永华　　E-mail: yhji@staff.shu.edu.cn

引用本文：

傅晋, 焦云露, 李正威, 吉永华. 脊髓5-HT3A受体对BmK I诱发的大鼠炎性痛的影响[J]. 生理学报 2015; 67 (3): 283-294.

FU Jin, JIAO Yun-Lu, LI Zheng-Wei, JI Yong-Hua. Spinal 5-HT3AR contributes to BmK I-induced inflammatory pain in rats. Acta Physiol Sin 2015; 67 (3): 283-294 (in Chinese with English abstract).