鞘内注射荷包牡丹碱和L-烯丙基甘氨酸对氯胺酮脊髓镇痛的影响  

Effect of intrathecal bicuculline and L-allylglycine on the spinal analgesia of ketamine in mice

作　　者：葛志军[1] 戴体俊[1] 曾因明[1] 段世明[1] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室

出　　处：《中国药理学与毒理学杂志》2005年第1期35-38,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目 (39970 715 ) ;江苏省自然科学基金资助项目 (BK2 0 0 114 3)~~

摘　　要：目的　在体研究脊髓GABAA 受体和氯胺酮(Ket)脊髓镇痛的关系 ,并初步探讨突触前、后机制在其中的作用。方法　用热水甩尾法和醋酸扭体法 ,观察鞘内注射 (ith)Ket(2 5 ,5 0 ,10 0 μg)对小鼠痛阈的影响。并用热水甩尾法观察GABAA 受体拮抗剂荷包牡丹碱 (Bic ,0 .0 5 ,0 .1,0 .2 μg ,ith) ,GABA合成酶抑制剂L 烯丙基甘氨酸 (AG ,2 0 0mg·kg- 1,ip)及两药合用对小鼠基础痛阈和Ket(10 0 μg ,ith)脊髓镇痛的影响。结果　Ket可产生剂量依赖性的镇痛作用。Bicith对小鼠痛阈无明显影响 ,但可明显减弱Ket的脊髓镇痛作用。ipAG或合用Bic(0 .0 5 ,0 .1μg,ith)对小鼠痛阈都无明显影响 ,而预先AGip可明显减弱Ket脊髓镇痛作用 ;且AGip后 ,Bic(0 .1μg ,ith)对Ket脊髓镇痛无明显拮抗作用。 结论　脊髓是Ket的镇痛部位之一 ,Ket的镇痛作用可能和Ket促进脊髓释放GABA有关。AIM To investigate the relationship between spinal GABA A re ce ptors and spinal analgesia of ketamine and determine whether the antinociceptive action of intrathecal ketamine on GABAergic neurons occur presynaptically or po stsynaptically. METHODS Antinociceptive tests in Kunming mice were investigated with tail-immersion test and acetic-induced writhing test. The ef fects of intrathecal (ith) ketamine on the pain threshold and the influence of p retreatment with GABA A receptor antagonist bicuculline (Bic, 0.05, 0.1, 0. 2 μ g), GABA synthesis inhibitor L-allylglycine(AG, 200 mg·kg - 1, ip) and their combination on the pain threshold and spinal analgesia of ket amine (100 μg) were observed. RESULTS Dose-dependent analgesia was observed following ith ketamine (50, 100 μg) . Bic ith alon e had no effect on the pain threshold. Bic ith (0.1, 0.2 μg) , but not 0.05 μg, significantly inhibited the spinal analgesia of ketamine. AG ip or the combination of AG and Bic (0.05, 0.1 μg, ith) had no effect on the p ain threshold. However, pretreatment with ip AG significantly reduced the spinal analgesia of ketamine. Furthermore, after pretreatment with AG, Bic (0.01 μg, ith) had no inhibitory effect on the spinal analgesia of ketamine. CONCLUS ION Spinal cord is one of the targets of ketamine analgesia. The spinal a nalgesia of ketamine is partly mediated by spinal GABA A receptors, possibly via a presynaptical mechanism in mice. But the direct action of ketami ne on spinal GABA A receptors may be of little importance to its analgesia.

关 键 词：氯胺酮 脊髓 镇痛 受体 GABA 

分 类 号：R96[医药卫生—药理学]