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马文俊,梁 英.A型肉毒毒素对膝骨性关节炎大鼠模型镇痛效果及机制的实验研究[J].中国康复医学杂志,2017,(6):649~653
A型肉毒毒素对膝骨性关节炎大鼠模型镇痛效果及机制的实验研究    点此下载全文
马文俊  梁 英
山西医科大学附属第一临床医学院,山西太原,030001
基金项目:山西省课题基金(201301055)
DOI:
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摘要:
      摘要 目的:评估A型肉毒毒素(BTX-A)在骨性关节炎模型中的镇痛效果及疼痛相关物质在脊神经节的变化,为其临床治疗骨性关节炎疼痛提供科学的理论依据。 方法:SD大鼠右膝关节腔内注射4%木瓜蛋白酶溶液0.3ml建立膝骨性关节炎(KOA)的动物模型。造模成功的大鼠于第2天随机分为2组:BTX-A组(n=10):关节腔内注射5μl BTX-A 0.1IU;WFI组(n=10):关节腔内注射5μl 注射用水;Sham组(n=10):非关节炎模型组。注射后第1、3、5天后检测疼痛行为学、热痛阈,免疫组织化学检测脊神经节钠离子通道1.8(Nav1.8)蛋白的表达。 结果:自发疼痛行为分析显示大鼠骨性关节炎引起步态异常,与WFI组相比,BTX-A组的大鼠异常步态改善明显,注射后5天与1、3天相比较,自发疼痛行为改善的愈明显;BTX-A组大鼠右足热痛阈升高(P<0.05),脊神经节Nav1.8蛋白表达下调(P<0.05)。 结论:关节腔内注射BTX-A可能通过下调脊神经节Nav1.8蛋白的表达,减少中枢致敏,减轻关节疼痛,提高痛阈,从而起到镇痛作用。
关键词:A型肉毒毒素  膝骨性关节炎  钠离子通道1.8  热痛阈  镇痛
An experimental research on the analgesic effect and underlying mechanism of BTX-A for rat knee osteoarthritis    Download Fulltext
Department of Rehabilitation Medicine,The First Clinical Hospital of Shanxi Medical University,Taiyuan,030001
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Abstract:
      Abstract Objective: To evaluate the analgesic effect of botulinum toxin type A (BTX-A) in osteoarthritis model and the changes of Nav1.8 protein expression in spinal ganglia changes. Method: Animal model of knee osteoarthritis (KOA) was established by intra-articular injection of 4% papain solution 0.3ml into SD rat right knee. After the formation of arthritis,they were randomly divided into two groups at the 2nd day: BTX-A group (n=10): intra-articular injection of 5μl BTX-A 0.1IU; WFI group (n=10): intra-articular injection of 5μl water. No papain or BXT-A was given to the sham group (n=10). At the 1st,3rd,5th day after injection,we tested the pain behavior, thermal pain threshold, and sodium channel 1.8 (Nav1.8) protein expression in spinal ganglion by using immunohistochemistry. Result: Analysis of spontaneous pain behavior showed abnormal gait caused by rat osteoarthritis. Comparing with the WFI group, abnormal gait caused by osteoarthritis improved significantly in BTX-A group. At day 5 it improved more significantly than day 1 and day 3. Thermal pain threshold of BTX-A group increased more than that of WFI group (P<0.05) at any time point. Abnormal high Nav1.8 protein in model rats decreased in spinal ganglia for BTX-A group. Conclusion:The intra-articular injection of BTX-A may play the analgesic effect in the model of KOA by down-regulating of the expression of Nav1.8 protein in spinal ganglia and reduction in the central sensitization to pain stimulation.
Keywords:botulinum toxin type A  knee osteoarthritis  Nav1.8 sodium channel  paw withdrawal latency  analgesia
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