蛛网膜下腔应用Ro 25-6981对神经病理痛大鼠的镇痛作用及其电生理学机制研究  

THE ANALGESIC EFFECTS OF INTRATHECAL ADMINISTRATION OF Ro 25-6981 ON NEUROPATHIC PAIN IN RATS:STUDY ON THE ELECTROPHYSIOLOGICAL MECHANISMS

作　　者：曲晓秀[1] 李鸣佳[1] 蔡捷[1] 郑琴[1] 池叶楠[1] 刘风雨[1] 万有[1] 韩济生[1] 邢国刚[1] 

机构地区：[1]北京大学神经科学研究所,基础医学院神经生物学系,教育部和卫生部神经科学重点实验室,北京100083

出　　处：《中国疼痛医学杂志》2008年第2期87-91,共5页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金(30370470);科技部国家重点基础研究发展计划“973”资助项目(2007CB512501)资助

摘　　要：目的:研究蛛网膜下腔应用Ro 25-6981,一种选择性的NMDA受体NR2B亚基(NR2B)的拮抗剂,对神经病理痛大鼠的镇痛作用及其可能的机制。方法:(1)雄性SD大鼠蛛网膜下腔置管,手术成功后进行L5脊神经结扎(SNL)手术。术后7天用vonFrey纤维丝测定机械痛敏,筛选出造模成功的SNL神经病理痛大鼠,随机分为三组,通过蛛网膜下腔插管分别鞘内给予(i.t.)Ro25-698110.0μg(20μl)、100.0μg(20μl),或等体积的生理盐水作对照。在给药后第30min、60min、90min和120min测定大鼠后爪的50%缩足阈值(PWT)及鞘内给药前后大鼠的运动功能。(2)通过在体细胞外记录的电生理学方法,观察脊髓背表面给予Ro 25-6981100.0μg对大鼠脊髓背角广动力范围(WDR)神经元放电的影响。结果:(1)与生理盐水组相比,鞘内应用Ro 25-698110.0μg对SNL大鼠的50%PWT和机械痛敏翻转百分率(%MPE)没有明显的影响(P>0.05,n=8),而100.0μg却能显著增加SNL大鼠的50%PWT和%MPE,起到明显的镇痛作用(P<0.05,n=8),并且在上述两种剂量下鞘内给药前后,动物的运动功能没有出现显著改变(P>0.05);(2)与生理盐水组相比,脊髓背表面给予Ro 25-6981100.0μg对WDR神经元的Aβ纤维诱发放电没有显著影响(P>0.05,n=6),但是可以显著抑制C纤维诱发放电(P<0.05,n=6)。结论:鞘内应用选择性的NR2B拮抗剂Ro 25-6981100.0μg可以对SNL大鼠产生明显的镇痛作用,而不影响动物的运动功能;这种镇痛作用可能是通过拮抗脊髓背角的NMDA受体NR2B亚基,进而抑制WDR神经元的C纤维诱发放电所产生的。Objective ： To investigate the potential mechanisms and the analgesic effects of intrathecal administration of Ro 25-6981, a selective antagonist of the NR2B subunit of NMDA receptors （ NR2B）, on neuropathic pain in rats. Methods ： （ 1 ） L5 spinal nerve ligations （SNL） were performed after intrathecal catheterizations were succeeded in male Sprague-Dawley rats. The rats with neuropathic pain evaluated by von Frey filaments-induced mechanical allodynia were divided into three groups randomly. Ro 25-6981 at the dose of 10 μg （20 μl） or 100 μg （20 μl）, or saline solution at the same volume, was administrated to rats in each group by intrathecal injection （ i. t. ）. The 50% paw withdrawal thresholds （PWT） of the rats were tested with von Frey filaments at 30 min, 60 min, 90 min, and 120 min after Ro 25-6981 or saline solution administration. And the locomotor functions were also examined by the slope board test at the same time points. （2） The effects of Ro 25-6981 on the discharges of spinal wide dynamic range （WDR） neurons were examined through in vivo extraeellular eleetrophysiologieal recording techniques in normal rats. Results： （1） Intratheeal injection of Ro 25-6981 at the dose of 10 μg did not show significant effects on 50% PWT and % MPE in SNL rats as compared with that i. t. the same volume of saline solution （p 〉 0.05, n = 8） ; while at the dose of 100 μg showed significant increases in 50% PWT and % MPE （P 〈 0.05, n = 8）. Moreover, no obvious impairment on locomotor function was observed after i.t. Ro 25-6981 at both of the above doses. （2） Spinal administration of Ro 25-6981 at the dose of 100 μg had no significant effect on Aβ-fiber evoked discharges of WDR neurons （P 〉 0.05, n = 6） , but showed significant enhance in C-fiber evoked discharges （P 〈 0.05, n = 6）. Conclusions ： Intrathecal injection of Ro 25-6981 at the dose of 100 μg had significant analgesic effects on rats with neuropathie pain, but didnt affect their

关 键 词：NMDA受体NR2B亚基 脊髓背角 神经病理痛 Ro 25-6981 

分 类 号：R96[医药卫生—药理学]