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抑制炎症大鼠前列腺素合成致阿片介导的痛觉减退

黄键, 吴检, 杨怀祖, 洪炎国^*

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 350117

摘要

本研究旨在探讨前列腺素在炎性痛维持中的作用。大鼠右侧足跖皮下注射角叉菜胶1 h后，于炎症局部注射环氧合酶非选择性抑制剂吲哚美锌，测定大鼠对伤害性热刺激的缩足反射潜伏期(paw withdrawal latency, PWL)。用免疫组织化学、ELISA和RT-PCR方法检测炎症组织中β-内啡肽(β-END)和μ-阿片受体(μ opioid receptor, MOR)的表达。结果显示，吲哚美锌能够剂量依赖性地延长大鼠在第2天和第3天的PWL，显著超过正常基础值，产生痛觉减退；吲哚美锌痛觉减退作用可被阿片受体非选择性抑制剂纳洛酮所翻转；吲哚美锌可显著提高模型大鼠炎症组织内β-END阳性细胞数量、β-END蛋白含量及MOR mRNA表达水平。本研究揭示了前列腺素致痛的新机制，即抑制炎症引起的内源性阿片活动，为开发以抑制外周炎症组织前列腺素为目标的镇痛药提供了新的理论依据。

关键词： 前列腺素; 炎性痛; 内源性阿片机制; 痛觉减退

Inhibition of prostaglandins synthesis in the inflamed site results in opioid-mediatedhypoalgesia in rats

HUANG Jian, WU Jian, YANG Huai-Zu, HONG Yanguo^*

College of Life Sciences, Fujian Normal University, Fujian Key Laboratory of Developmental and Neurological Biology, Fuzhou350117, China

Abstract

This study was designed to investigate the contribution of prostaglandins to the maintenance of inflammatory pain. Inflammation was induced by intraplantar (i.pl.) injection of carrageenan in right hindpaw in rats. Indomethacin (non-selective COX inhibitor) was administered i.pl. 1 h after the carrageenan injection, and paw withdrawal latency (PWL) responding to noxious heat was measured. β-endorphin (β-END) and μ-opioid receptor (MOR) expressed in the inflamed site were examined by using immunocytochemistry, ELISA and RT-PCR techniques. The results showed that indomethacin dose-dependently increased PWL to the levels that were above the baseline on the day 2 and 3, referred to as hypoalgesia. The hypoalgesia was abolished by a local injection of the non-selective opioid receptor inhibitor naloxone methiodide. The number of β-END-positive cells, the content of β-END and the expression of MOR mRNA in the inflammatory site of inflammation model rats were all significantly increased by indomethacin. These results reveal a novel mechanism of prostaglandins for the inhibition of inflammation-induced endogenous opioid activity. Thisstudy provides further evidence that inhibition of prostaglandins in inflamed site could be a promising therapy for inflammatory pain.

Key words: prostaglandins; inflammatory pain; endogenous opioid mechanism; hypoalgesia

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通讯作者：洪炎国　　E-mail: yhong@fjnu.edu.cn

引用本文：

黄键, 吴检, 杨怀祖, 洪炎国. 抑制炎症大鼠前列腺素合成致阿片介导的痛觉减退[J]. 生理学报 2016; 68 (3): 241-248.

HUANG Jian, WU Jian, YANG Huai-Zu, HONG Yanguo. Inhibition of prostaglandins synthesis in the inflamed site results in opioid-mediatedhypoalgesia in rats. Acta Physiol Sin 2016; 68 (3): 241-248 (in Chinese with English abstract).