鞘内注射巴氯芬对神经病理性痛大鼠的镇痛作用及其对脊髓γ-氨基丁酸转运体-1的影响  

Anti-hyperalgesic effect of intrathecall injection of baclofen on neuropathic pain of rats and its effects on the expression of GAT-1 in the spinal cord

作　　者：严蓉[1] 朱珊珊[1,2] 聂鑫[1] 张励才[1] 曾因明[1] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室 [2]221005徐州市第三人民医院麻醉科

出　　处：《国外医学（麻醉学与复苏分册）》2005年第3期133-137,共5页Foreign Medical Sciences(Anesthesilolgy and Resuscitation)

基　　金：江苏省教育厅开放课题资助项目(KJS02054)

摘　　要：目的通过行为学和形态学方法检测GABAB受体激动剂巴氯芬对大鼠痛阈及脊髓γ-氨基丁酸转运体-1(γ-ami-nobutyricacidtransporter-1,GAT-1)表达的影响,探讨巴氯芬影响神经病理性痛的作用机制。方法行为学实验,建立慢性坐骨神经结扎损伤模型,神经结扎后3d形成神经病理性痛的32只SD大鼠随机分为4组(n=8):NS组,Bac1组,Bac2组,Bac3组,鞘内分别注射生理盐水、0·1μg、0·3μg或1·0μg巴氯芬,注射容积均为10μL。分别于给药前、给药后0·5h、1h、2h、4h、8h、12h、24h测大鼠机械缩足反射阈值(mechanicalwithdrawalthreshold,MWT)和热缩足反射潜伏期(thermalwithdrawallatency,TWL)以及运动功能。形态学实验,坐骨神经结扎后3d形成神经病理性痛的60只SD大鼠随机分为2组:Bac组和NS组,鞘内分别给予0·3μg巴氯芬或生理盐水10μl,分别于给药前、给药后1、4、8、24h取大鼠脊髓腰段,用免疫组织化学方法检测脊髓背角GAT-1的表达。结果Bac1组、Bac2组与Bac3组大鼠MWT和TWL均较NS组及给药前均明显升高(P<0·01,P<0·05);其效应分别持续2h、4h、8h。鞘内注射巴氯酚1·0μg,大鼠运动功能有不同程度受损。鞘内注射巴氯酚0·3μg后1h、4h,脊髓背角GAT-1灰度值明显降低,与NS组和给药前比较有统计学差异(P<0·05)。结论巴氯芬在神经病理性痛大鼠具有抗痛觉过敏的作用,脊髓GAT-1的表达减少参与其中的调节。Objective To investigate the effect of baclofen on γ-aminobutyric acid transporter-1(GAT-1)in the spinal cord in a rat of neuropathic pain. Methods On the chronic constriction injury (CCI) rats, 32 rats were randomly divided into four groups (n=8): NS group, Bac1 group, Bac2 group and Bac3 group. Normal saline, 0.1 μg, 0.3 μg or 1.0 μg baclofen were intrathecally injected respectively on 3rd day after operation. MWT and TWL were measured before and on 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 1 d after intrathecally injection. For the immunohistochemical study, 60 neuropathic rats were randomly divided into 2 groups: Bac group and NS group, 0.3 μg baclofen or normal saline were intrathecally injected in a volume of 10 μl respectively on 3 rd day after operation and lumbar spinal cord was removed before or 1 h, 4 h ,8 h and 24 h respectively after intrathecally injection. Results Intrathecal injection of baclofen significantly suppressed thermal hyperalgesia and tactile allodynia in neuropathic rats, the inhibitive effects lasted for 2 h(Bac1 group), 4 h(Bac2 group)and 8 h(Bac3 group)respectively. 1.0 μg baclofen produced significant ambulation deficits. Relative immunoreactive densities of GAT-1 were decreased on 1h and 4 h after intrathecal injection of 0.3 μg baclofen. Conclusion Intrathecal injection of baclofen has anti-thermal hyperalgesia and anti-tactile allodynia effects in neuropathic rats and down regulation of GAT-1 in spinal cord was involved in.

关 键 词：Γ-氨基丁酸转运体 神经病理性痛 鞘内注射 巴氯芬 镇痛作用 GABAB受体激动剂 免疫组织化学方法 SD大鼠 生理盐水 运动功能 脊髓背角 形态学方法 行为学实验 形态学实验 统计学差异 给药前 acid 作用机制 损伤模型 神经结扎 

分 类 号：R741[医药卫生—神经病学与精神病学]