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加巴喷丁治疗大鼠腰5神经结扎后神经病理性疼痛的疗效及可能机制 被引量:7

Efficacy and possible mechanism of gabapentin in treating the neuropathic pain induced by L_5 spinal nerve ligation in rats
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摘要 目的观察加巴喷丁(gabapentin,GBP)对大鼠腰5神经结扎(spinal nerve ligation,SNL)后神经病理性疼痛(neuropathic pain,NPP)的疗效及其对脑及腰段脊髓细胞因子和脊髓核因子-κB(nuclear factor-kappa B,NF-κB)表达的影响。方法 30只大鼠随机分为5组(n=6),即假手术对照组、SNL对照组、SNL+小剂量GBP组、SNL+中剂量GBP组和SNL+大剂量GBP组。术后第5天,假手术对照组和SNL对照组给予等渗盐水,SNL+小剂量GBP组、SNL+中剂量GBP组和SNL+大剂量GBP组分别给予GBP100、200和400 mg/kg灌胃治疗。术前1 d、给药前1 h、给药后2、4、6、8 h分别测定左后肢回缩压力阈值(paw withdrawal pressure threshold,PWPT)和回缩潜伏期(pawwithdrawal latency,PWL)。给药后9h取大鼠右脑及腰段脊髓,检测肿瘤坏死因子α(tumor hecrosing factorα,TNF-α)、白细胞介素(interleukin,IL)-6、IL-10表达和腰段脊髓NF-κB的活性。结果①左后肢痛阈改变:与假手术对照组比,SNL对照组、SNL+小剂量GBP组、SNL+中剂量GBP组、SNL+大剂量GBP组术后PWPT和PWL均下降(P<0.01);与SNL对照组比,GBP治疗后SNL+小剂量GBP组PWPT和PWL在给药后2 h,SNL+中剂量GBP组在给药后2、4 h,SNL+大剂量GBP组在给药后2、4、6、8 h,PWPT和PWL上升(P<0.05)。与SNL+小剂量GBP组、SNL+中剂量GBP组比较,SNL+大剂量GBP组在给药后4、6、8hPWPT和PWL上升(P<0.05)。②右脑及腰段脊髓细胞因子改变:与假手术对照组比,SNL对照组、SNL+小剂量GBP组、SNL+中剂量GBP组和SNL+大剂量GBP组右脑和腰段脊髓TNF-α、IL-6及IL-10表达上升(P<0.05)。与SNL对照组比,SNL+大剂量GBP组右脑和腰段脊髓TNF-α、IL-6表达下降,IL-10表达上升(P<0.01);SNL+中剂量GBP组腰段脊髓TNF-α、IL-6表达下降,IL-10表达上升(P<0.05)。③腰段脊髓NF-κB改变:与假手术对照组比,SNL对照组、SNL+小剂量GBP组、SNL+中剂量GBP组和SNL+大剂量GBP组NF-κB活性上升(P<0.01)。与SNL对照组比,SNL+中剂量GBP组和SNL+大剂量GBP组N Objective To observe the efficacy of gabapentin(GBP) in treating the neuropathic pain(NPP) induced by L5 spinal nerve ligation(SNL) and the expressions of cytokines and NF-κB in brain and spinal cord in rats.Methods Thirty male SD rats were randomized into 5 groups(n= 6): sham operation control group,SNL control group,SNL+small dose of GBP group,SNL+median dose of GBP group and SNL+large dose of GBP group.The rats in 2 control groups received normal saline and the rats in 3 GBP groups received 100,200,and 400 mg/kg dose of GBP via intragastric administration on d 5 after SNL,respectively.Paw withdrawal pressure threshold(PWPT) and paw withdrawal latency(PWL) of the left paws were measured 1 d before operation,1 h before intragastric administration,and 2,4,6,8 h after intragastric administration.Right brain and lumbar spinal cord were obtained 9 h after intragastric administration to determine the expressions of TNF-α,IL-6,IL-10,and NF-κB.Results ①Changes of pain thresholds of the left hind paws: Compared with sham operation control group,PWPT and PWL decreased in SNL control group,SNL+small dose of GBP group,SNL+median dose of GBP group,and SNL+large dose of GBP group(P0.01).Compared with SNL control group,PWPT and PWL increased at 2 h in SNL+small dose of GBP group,at 2 and 4 h in SNL+median dose of GBP group,and at 2,4,6,and 8 h in SNL+large dose of GBP group,respectively(P0.05).Compared with SNL+small dose of GBP group and SNL+median dose of GBP group,PWPT and PWL increased at 4,6,and 8 h in SNL+large dose of GBP group(P0.05).②Changes of cytokines in right brain and lumbar spinal cord: Compared with sham operation control group,TNF-α,IL-6,and IL-10 increased in SNL control group,SNL+small dose of GBP group,SNL+median dose of GBP group,and SNL+large dose of GBP group(P0.05).Compared with SNL control group,TNF-α and IL-6 decreased,and IL-10 increased in right brain and lumbar spinal cord in SNL+large dose of GBP group(P0.01�
出处 《医学研究生学报》 CAS 2010年第5期465-469,共5页 Journal of Medical Postgraduates
基金 中国博士后科学基金(2006040937)
关键词 加巴喷丁 神经病理性疼痛 核因子-ΚB 肿瘤坏死因子-α 白细胞介素-6 白细胞介素-10 Gabapentin Neuralgia Nuclear factor-kappa B Tumor hecrosing factor α Interleukin-6 Interleukin-10
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