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鞘内注射孤啡肽对大鼠足底注入蜜蜂毒诱致长时程自发痛、痛敏和炎症的不同效果

孙焱芫, 罗层, 李震, 陈军

第四军医大学全军神经科学研究所疼痛研究中心. 西安 710032

摘要

为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观察了新的高选择性孤啡肽受体拮抗剂CompB的作用.结果表明:与生理盐水对照组比较,鞘内注射孤啡肽(3、10、30 nmol/10μl)对蜜蜂毒诱发的自发缩足反射次数的抑制作用随剂量提高而增大,抑制率分别为37±7,43±6and57±11%(三个剂量vs对照,P＜0.05);而对蜜蜂毒诱发的注射部位炎症反应(爪体积、爪背腹厚度和蛋白渗出的增加)无显著影响.CompB(30 nmo1)可完全翻转10 nmol孤啡肽对自发缩足反射的抑制作用.鞘内单次或重复注射孤啡肽(10 nmol/10μl)对蜜蜂毒诱致的原发性热和机械性痛敏的发生和维持均无作用.本实验结果提示,外源性孤啡肽在脊髓通过孤啡肽受体的介导产生一定的镇痛作用,但是它可能仅对持续性自发痛有抑制作用,而对热和机械性痛敏及炎症反应均无影响。

关键词： 孤啡肽; 蜜蜂毒试验; 持续性自发痛; 痛敏; 炎症; 抗伤害作用; 抗炎作用

Differential actions of intrathecal nociceptin on persistent spontaneous nociception, hyperalgesia and inflammation produced by subcutaneous bee venom injection in conscious rats

Sun Yanyan, Luo Ceng, Li Zhen, Chen Jun

Pain Research Center, Institute of Neuroscience, The Fourth Military Medical University. Xi'an 710032, China

Abstract

Nociceptin is an endogenous ligand for the opioid receptor-like 1 (ORL1) receptor. The present study was designed to investigate spinal actions of nociceptin on the spontaneous nociception, hyperalgesia and inflammation induced by subcutaneous bee venom injection.Subcutaneous injection of bee venom into one hindpaw of conscious rat produced a persistent spontaneous nociception followed by a longlasting primary heat and mechanical hyperalgesia as well as local inflammation. Compared with the pre-saline group, pretreatment with intrathecal injection of three doses (3, 10 and 30 nmol) of nociceptin produced significant suppression on the spontaneous paw flinching reflex.The inhibitory rates were 37±7, 43±6 and 57±11%, respectively, which were enhanced with an increase in the concentration of nociceptin. The inhibitory action of nociceptin was completely antagonized by a new selective ORL1 receptor antagonist CompB (30 nmol). Pre-treatment with 10 mol nociceptin prior to bee venom produced no significant effect on the oc currence of primary heat and mechanical hyperalgesia, nor did post-treatment with the same dose again 3 h after bee venom injection. Additionally, pre-treatment with nociceptin had no effect on the bee venom-induced increase in paw thickness and volume and the plasma protein extravasation. These results indicate that intrathecal nociceptin has no effect on primary heat and mechanical hyperalgesia as well as inflammation, but has dose-related anti-nociceptive effect on the bee venom-induced persistent spontaneous nociception via activation of spinal ORL1 receptor.

Key words: Nociceptin;Bee venom test;Persistent spontaneous pain;Hyperalgesia;Inflammation;Anti-nociception;Anti-inflammation

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引用本文：

孙焱芫, 罗层, 李震, 陈军. 鞘内注射孤啡肽对大鼠足底注入蜜蜂毒诱致长时程自发痛、痛敏和炎症的不同效果[J]. 生理学报 2004; 56 (3): .

Sun Yanyan, Luo Ceng, Li Zhen, Chen Jun. Differential actions of intrathecal nociceptin on persistent spontaneous nociception, hyperalgesia and inflammation produced by subcutaneous bee venom injection in conscious rats. Acta Physiol Sin 2004; 56 (3): (in Chinese with English abstract).