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阻断炎症部位5-HT2A受体对大鼠完全弗氏佐剂诱发炎性痛和脊髓背角神经肽Y表达的作用

黄冰晴, 吴冰, 洪炎国, 胡薇^*

福建师范大学生命科学学院，福建省发育和神经生物学重点实验室，福州 350108

摘要

炎症时组织释放5-羟色胺(5-hydroxytryptamine, 5-HT)，对炎性痛觉过敏的产生起重要作用。但炎症组织5-HT2A受体在其中的意义尚不明确。本文旨在研究外周组织5-HT2A受体在慢性炎性痛中的作用。大鼠后足底注射完全弗氏佐剂(complete Freund’s adjuvant, CFA)，在局部炎性部位给予选择性5-HT2A受体阻断剂酮色林，用行为学检测后足底对热和机械刺激的撤足反射，用免疫组织化学方法检查脊髓背角和背根神经节(dorsal root ganglion, DRG)中神经肽Y (neuropeptide Y, NPY)表达变化。结果显示，炎症局部给予酮色林(20、40、80 µg)能剂量依赖性地抑制CFA诱发的热痛觉过敏；每日给予80 µg酮色林，在第三天即完全翻转CFA引起的热痛觉过敏，以及部分地减轻触觉超敏。CFA诱发脊髓背角I~II层 NPY表达增加，炎症组织局部注射酮色林能抑制脊髓背角NPY的表达增加，但不改变DRG中NPY的表达。这些结果表明：外周炎症组织5-HT2A受体激活参与慢性痛觉过敏的发生；阻断炎症部位5-HT2A受体能缓解疼痛，矫正与病理疼痛密切关联的脊髓背角细胞异常改变。因此，外周5-HT2A受体，有望成为治疗慢性炎性痛觉敏感性增高、不产生中枢神经系统副作用的药物靶点。

关键词： 酮色林; 5-HT2A受体; 慢性炎性痛; 脊髓背角; 神经肽Y

分类号：Q426;R338.3

[Effects of blockade of 5-HT2A receptors in inflammatory site on complete Freund’s adjuvant-induced chronic hyperalgesia and neuropeptide Y expression in the spinal dorsal horn in rats.] [Article in Chinese]

HUANG Bing-Qing, WU Bing, HONG Yanguo, HU Wei^*

Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University, Fuzhou 350108, China

Abstract

5-hydroxytryptamine (5-HT) released in inflammatory tissues plays a pivotal role in pain hypersensitivity. However, it is not clear whether 5-HT2A receptors in the inflamed tissues mediate this effect. The present study investigated the contribution of 5-HT2A receptors in the periphery to chronic inflammatory pain. Complete Freund’s adjuvant (CFA) was injected subcutaneously in the hindpaw of rats. The selective 5-HT2A receptor antagonist ketanserin was given in the inflamed site. Paw withdrawal latency responding to heat or mechanical stimuli was measured. Expression of neuropeptide Y (NPY) in the spinal dorsal horn and dorsal root ganglia (DRG) was assayed using immunohistochemistry technique. The results showed that ketanserin administered in the inflamed site inhibited thermal hyperalgesia in a dose-dependent manner (20, 40 and 80 µg) induced by the intraplantar injection of CFA. Ketanserin given once per day at a dose of 80 µg abolished heat hyperalgesia and also attenuated mechanical allodynia on the third day. CFA injection increased the expression of NPY in superficial laminae of the spinal cord, but not in the DRG. The local treatment of ketanserin completely inhibited CFA-induced increase in NPY expression in superficial laminae of the spinal cord. These results indicated that activation of 5-HT2A receptors in the inflamed tissues was involved in the pathogenesis of inflammatory pain and the blockade of 5-HT2A receptors in the periphery could relieve pain hypersensitivity and normalize the cellular disorder in the spinal dorsal horn associated with pathological pain. The present study suggests that the peripheral 5-HT2A receptors can be a promising target for pharmaceutical therapy to treat chronic inflammatory pain without central nervous system side effects.

Key words: ketanserin; 5-HT2A receptor; chronic inflammatory pain; spinal dorsal horn; neuropeptide Y

收稿日期：2015-04-08　　录用日期：2015-06-12

通讯作者：胡薇　　E-mail: huwei@fjnu.edu.cn

引用本文：

黄冰晴, 吴冰, 洪炎国, 胡薇. 阻断炎症部位5-HT2A受体对大鼠完全弗氏佐剂诱发炎性痛和脊髓背角神经肽Y表达的作用[J]. 生理学报 2015; 67 (5): 463-469.

HUANG Bing-Qing, WU Bing, HONG Yanguo, HU Wei. [Effects of blockade of 5-HT2A receptors in inflammatory site on complete Freund’s adjuvant-induced chronic hyperalgesia and neuropeptide Y expression in the spinal dorsal horn in rats.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (5): 463-469 (in Chinese with English abstract).