文章摘要
鞘内注射PDTC对神经病理性痛大鼠TRPM8受体表达的影响
Effects of transient receptor potential channel 8 with intrathecal injection of PDTC in rats with neuropathic pain
  
DOI:10.12089/jca.2018.11.015
中文关键词: 瞬时受体电位通道  TRPM8  神经痛  神经节, 脊  NF-κB
英文关键词: Transient receptor potential channels  TRPM8  Neuralgia  Ganglia, spinal  NF-kappa B
基金项目:国家自然科学基金(81450054);贵州省科技厅联合基金([2014]7583)
作者单位E-mail
李周睿 563000,贵州省遵义医学院附属医院疼痛科(现在常州市第二人民医院)  
曹欣娅 563000,贵州省遵义医学院附属医院疼痛科  
秦榜勇 563000,贵州省遵义医学院附属医院疼痛科 qbyzy@163.com 
李清梅 563000,贵州省遵义医学院附属医院麻醉科  
刘晓红 遵义医学院基础医学院生理学教研室  
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中文摘要:
      
目的 探讨NF-κB参与TRPM8受体在大鼠神经病理性痛觉调制中的作用。
方法 鞘内置管成功的SPF级健康雄性SD大鼠36只, 4~6周龄, 体重180~200 g, 采用随机数字表法分为三组: 假手术组(S组)、神经病理性痛组(NP组)和NF-κB阻滞剂PDTC组(PDTC组), 每组12只。鞘内置管成功后第3天, NP组和PDTC组采用坐骨神经缩窄性损伤(chronic constriction injury, CCI)法制备大鼠神经病理性痛模型; S组只游离坐骨神经不做损伤处理。三组大鼠术后1 d开始连续鞘内注射, 连续14 d(2次/天), PDTC组鞘内注射PDTC 20 μg/10 μl(20 μg PDTC溶于10 μl生理盐水), 注射完成后10 μl生理盐水冲管, S组和NP组分别鞘内注射等容量生理盐水, 三组大鼠分别于术前1 d、术后1、3、7、10和14 d鞘内给药后30 min测定冷痛阈、热痛阈和机械痛阈。分别在术后7、14 d处死大鼠, 采用Western blot法检测背根神经节(DRG)中TRPM8受体和NF-κB p65蛋白含量。
结果 与S组比较, 术后1~14 d NP组冷痛阈明显降低、热痛阈明显缩短、机械痛阈明显降低(P<0.05); 与NP组比较, 术后3~14 d PDTC组冷痛阈明显增多、热痛阈明显延长、机械痛阈明显升高(P<0.05)。与S组比较, 术后7、14 d NP组TRPM8受体和NF-κB p65蛋白含量明显升高(P<0.05); 与NP组比较, 术后7、14 d PDTC组TRPM8受体和NF-κB p65蛋白含量明显降低(P<0.05)。
结论 大鼠DRG中TRPM8和NF-κB p65表达上调参与神经病理性痛的发生发展, 抑制NF-κB活化可以减少TRPM8受体的表达上调并且改善大鼠痛觉过敏的症状。
英文摘要:
      
Objective To investigate the mechanism and the role of transient receptor potential channel 8 with the involvement of nuclear factor kappa B in modulation of neuropathic pain in rats.
Methods Thirty-six special pathogen-free healthy adult male Sprague-Dawley rats with successful intrathecal catheter implantation, weighing 180 - 200 g, aged 4 - 6 weeks, were divided into 3 groups (n=12 each) by using a random number table, respectively, sham operation group (group S), neuropathic pain group (group NP) and NF-κB bocker PDTC group (group PDTC). The third day after intrathecal catheter was successfully implanted, neuropathic pain model was made from group NP and group PDTC based on chronic constriction injury (CCI), Group S was only isolated the trunk of sciatic nerve without ligation. PDTC 20 μg/10 μl (20 μg PDTC was dissolved in physiological saline) was intrathecally injected twice a day on the 1st postoperative day and the injection lasted for the next 13 days in the three groups. After the injection, 10 μl physiological saline was used to rinse. Group S and group NP were intrathecally injected equal volume of physiological saline and 30 minutes after intrathecal administration, the cold pain, thermal, and mechanical thresholds were measured on preoperative day 1 and postoperative days 1, 3, 7, 10 and 14 in the three groups. The rats were dispatched and the dorsal root ganglions were removed 7 and 14 days after operation for determination of the expression of TRPM8 and NF-κB p65 by Western blot.
Results The cold pain, thermal, and mechanical thresholds were significantly decreased on the first postoperative day of constriction injury and the case continued for the next 13 days. The expression of TRPM8 and NF-κB p65 in dorsal root ganglions was significantly increased 7 and 14 days after operation in group NP. The hyperalgesia was remarkably reduced 3-14 days after operation in PDTC. The intrathecally-injected NF-κB blocker could effectively block the up-regulation of the expression of NF-κB p65 and TRPM8 in dorsal root ganglions.
Conclusion The up-regulation of expression of TRPM8 and NF-κB p65 in dorsal root ganglions is associated with neuropathic pain, and inhibiting the activation of NF-κB can relieve the up-regulation of the expression of TRPM8 as well as the hyperalgesia of rats.
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