中脑导水管周围灰质5-HT_7受体在神经病理性疼痛中的镇痛作用研究  

THE ANALGESIC EFFECT OF 5-HT_7 RECEPTOR IN MIDBRAIN PERIAQUEDUCTAL GRAY ON NEUROPATHIC PAIN RATS

作　　者：肖智[1] 文松[2] 

机构地区：[1]遵义医学院医学与生物学研究中心,遵义563000 [2]遵义医学院研究生学院,2011级遵义563000

出　　处：《中国疼痛医学杂志》2014年第12期861-865,共5页Chinese Journal of Pain Medicine

基　　金：贵州省科学技术基金项目[黔科合J字[2011]2123号)]

摘　　要：目的:探讨神经病理性疼痛大鼠中脑导水管周围灰质外侧区(l PAG)中5-羟色胺7(5-HT7)受体活化在神经病理性疼痛中的镇痛作用。方法:SD大鼠60只,均分为5组:正常组、神经病理性疼痛组(CCI组)、假CCI组、CCI加AS-19和CCI加SB-269970组。制备CCI大鼠模型,检测各组大鼠机械痛阈变化;免疫印迹法检测l PAG中5-HT7受体蛋白表达情况;在CCI大鼠l PAG中微量注射5-HT7受体特异性激动剂AS-19(6μmol/0.3μl)以及特异性拮抗剂SB-269970(3μmol/0.3μl)后观察药物对CCI大鼠机械痛阈的影响。结果:神经病理性疼痛大鼠机械痛阈下降伴l PAG中5-HT7受体蛋白表达上调,与假手术组大鼠比较差异有统计学意义(P<0.001)。CCI大鼠l PAG注射AS-19后,机械痛阈显著上升(P<0.001)且可被预先注射SB-269970所抑制。结论:l PAG中5-HT7受体活化后通过激活机体内源性镇痛系统对神经病理性疼痛大鼠产生镇痛作用。Objective： To investigate the analgesic role of 5-HT7 receptor in lateral midbrain periaqueductal gray （1PAG） on neuropathic pain rats. Methods： Sixty male Sprague-Dawley （SD） rats were randomly divided into 5 groups： normal, chronic constriction injury （CCI）, sham CCI, CCI ＋ AS-19 and CCI ＋ SB-269970 groups. The rat neuropathic pain model was established by right sciatic nerve chronic constriction and the pain threshold was characterized by the mechanical withdrawal threshold （MWT） testing. The 5-HT7 receptor protein expression in 1PAG was analyzed by Wetsem blotting. The effect of pretreatment with SB-269970 （3 μmol/0.3 μl） on the analgesic effect of IPAG microinjection of AS-19 （6 μtmol/0.3 μl） was also obesrved. Results： The CCI rats hind-paw MWT values were gradually decreased after CCI operation. The sciatic nerve ligation caused significant increase of 5-HT7 protein level in the rats IPAG compared with normal group （P〈 0.001）; 1PAG microinjection of AS-19 significantly elevated MWT （P 〈 0.001）, and the antinociceptive effect of AS-19 was partly counteracted by SB-269970 pretreatment. Conclusions： The expression change of 5-HT7 receptor in the IPAG and the elevated MWT values after intra-PAG injection of AS-19 indicate that 5-HT7 receptors in the 1PAG play an analgesic effect in the neuropathic pain modulation which may serve as a central target for analgesics.

关 键 词：神经病理性疼痛 中脑导水管周围灰质外侧区 5-HT7受体 

分 类 号：R741[医药卫生—神经病学与精神病学]