鞘内注射巴氯酚对神经病理性痛大鼠的镇痛作用及其对脊髓GABA转运体-1的影响  

Effects of intrathecal injection of GABA_B receptor agonist baclofen on hyperalgesia and spinal GAT-1 of neuropathic rats

作　　者：朱珊珊[1,2] 谭珊珊[1,2,3] 曾因明[3] 

机构地区：[1]徐州市肿瘤医院 [2]江苏大学附属徐州医院麻醉科,江苏徐州221005 [3]徐州医学院江苏省麻醉医学研究所,江苏徐州221002

出　　处：《中国药理学通报》2011年第10期1443-1447,共5页Chinese Pharmacological Bulletin

基　　金：江苏省重点实验室开放课题资助项目(NoKJS050002);江苏大学临床医学科技发展基金资助项目(NoJLY2010050);徐州市科技局课题基金资助项目(NoXM07C045)

摘　　要：目的研究鞘内注射GABAB受体激动剂巴氯酚(ba-clofen,Bac)对神经病理性痛大鼠的镇痛作用及其对脊髓GABA转运体-1的影响。方法建立坐骨神经结扎致神经病理性痛大鼠模型。在行为学实验部分,将32只大鼠随机分为NS组、Bac1组、Bac2组、Bac3组(n=8),分别鞘内注射生理盐水、0.1、0.3、1.0μg巴氯酚10μl,并分别于给药前、给药后0.5、1、2、4、8、12、24 h测定大鼠机械缩足反射阈值(mechanical withdrawl threshold,MWT)和热缩足反射潜伏期(thermal withdrawl latency,TWL)以及运动功能。在第2部分,将大鼠分为NS组与Bac组,鞘内分别给予0.3μg巴氯酚或生理盐水,分别于给药前、给药后1、4、8 h取大鼠脊髓腰段,免疫组织化学检测脊髓节段GAT-1免疫阳性神经元(n=6);分别于给药前、给药后30 min、1、2、4、8、12和24 h取大鼠脊髓腰段,用Western blot方法测定脊髓节段GAT-1蛋白含量(n=4)。结果鞘内注射巴氯酚后0.5～2 h,Bac1组、Bac2组与Bac3组大鼠MWT和TWL均较NS组明显升高(P<0.01,P<0.05),鞘内给药后4 h,Bac2与Bac3组大鼠MWT和TWL仍较NS组明显升高(P<0.01,P<0.05),给药后8 h,Bac3组MWT与TWL仍高于NS组(P<0.05)。与NS组和给药前比较,鞘内注射0.3μg巴氯酚后0.5～4h,大鼠脊髓节段的GAT-1蛋白含量均明显降低(P<0.01,P<0.05),大鼠脊髓背角浅层GAT-1免疫阳性染色灰度值亦明显降低(P<0.01,P<0.05),至给药后8 h,GAT-1的表达逐渐增多,与NS组和给药前相比差异均无统计学意义(P>0.05)。结论鞘内注射GABAB受体激动剂巴氯酚可减轻坐骨神经结扎致神经病理性痛大鼠的痛觉过敏,其镇痛作用可能与抑制脊髓水平GAT-1的表达有关。Aim To explore the effects of intrathecal injection of GABAB receptor agonist baclofen on hyperalgesia and spinal GAT-1 of neuropathic rats induced by chronic constriction of sciatic nerve.Methods The left common sciatic nerve of anesthetized rats was tied loosely to establish the chronic constriction injury（CCI） model.For the behavioral experiments,32 rats exhibiting neuropathic pain after nerve ligation were divided into 4 groups（n=8）： NS group,Bac1 group,Bac2 group and Bac3 group,which were intrathecally injected with normal saline,0.1,0.3 and 1.0 μg baclofen respectively.MWT（mechanical withdrawl threshold）and TWL（thermal withdrawl latency） were recorded before drug administration,0.5,1,2,4,8,12 h and 24 h after drug administration respectively.For the immunohistochemical and Western blot experiment,neuropathic rats were divided into NS group and Bac group,which were intrathecally injected with normal saline or 0.3 μg baclofen respectively.Lumbar spinal cord of rats were removed before injection or 1,4 and 8 h after intrathecal injection respectively to detect the GAT-1 immunoreactive neurons（n=6） or were removed before injection or 0.5,1,2,4,8,12 h and 24 h after intrathecal injection respectively to detect the protein content of GAT-1（n=4）.Results MWT and TWL of Bac1,Bac2 and Bac3 group were significantly higher than those of NS group（P0.01,P0.05）.Compared with NS group,the increases of MWT and TWL in Bac1,Bac2 and Bac3 group were maintained until 8h after baclofen injection（P0.01,P0.05）.Compared with NS group and pre-drug values,both immunoreactive neurons and protein content of GAT-1 remarkably decreased during 0.5~4 h after drug administration.On 8h after drug administration,there were no significant differences in the expression of GAT-1 among the four groups（P0.05）.Conclusion Intrathecal injection of GABAB receptor agonist baclofen alleviates hyperalgesia of neuropathic rats with chronic constriction injury,which may be related to the down-regulation of spinal GAT

关 键 词：疼痛 慢性压迫损伤 脊髓 Γ-氨基丁酸转运体 巴氯酚 鞘内 

分 类 号：R-332[医药卫生] R322.81