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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 effects of baclofen, a GABAB receptor agonist, on the pain threshold and the expression of γ-aminobutyric acid transporter-1 (GAT-1) in the spinal cord of rats by behavioral and morphological methods. To investigate the mechanism of action of baclofen on neuropathic pain. Methods To establish a chronic lumbar sciatic nerve ligation injury model and 32 neuropathic pain-induced neuropathic pain rats were randomly divided into 4 groups (n = 8): NS group, Bac1 group, Bac2 group, Bac3 group, Saline, 0.1 μg, 0.3 μg or 1.0 μg baclofen were injected intraperitoneally. The volume of injection was 10 μL. The mechanical contraction threshold (MWT) and thermal latency (TWL), as well as the motor response of rats were measured before administration, at 0. 5h, 1h, 2h, 4h, 8h, 12h, Features. Morphological experiments: Sixty SD rats with neuropathic pain formed after ligation of sciatic nerve were randomly divided into two groups: Bac group and NS group. Each group received either 0.3 μg baclofen or saline 10μl before intrathecal administration The lumbar spinal cord of rats were taken at 1, 4, 8 and 24 hours after administration, and the expression of GAT-1 in spinal dorsal horn was detected by immunohistochemistry. Results The MWT and TWL in Bac1, Bac2 and Bac3 groups were significantly higher than those in NS group and before administration (P <0.01 or P <0.05), respectively. The effects were continued for 2h, 4h and 8h respectively. Intrathecal injection of 1μg of barium phenol, motor function in rats with varying degrees of damage. The gray value of GAT-1 in the dorsal horn of spinal cord decreased significantly at 1 h and 4 h after intrathecal injection of 0.4 mg BPP, which was significantly different from that before NS administration (P <0.05). Conclusion Baclofen has antihyperalgesic effects in neuropathic pain rats, and the expression of GAT-1 in the spinal cord is reduced and involved in the regulation.