普瑞巴林对神经病理性疼痛模型小鼠镇痛催眠作用的影响

发布时间：2018-11-02 20:44

【摘要】：目的：神经病理性疼痛是指由躯体感觉神经系统的损伤或疾病而直接引起的疼痛综合征，通常呈慢性，患者常伴有由于痛觉引发不同程度的睡眠障碍和情绪异常。普瑞巴林（Pregabalin，PGB）为γ-氨基丁酸（Gamma-aminobutyric acid，GABA）类药物，作为一种癫痫病的治疗药物在英美等国已成功上市。本课题拟在成功建立动物神经病理性疼痛（坐骨神经部分结扎）模型的基础上，深入的考察普瑞巴林对神经病理性疼痛及其引起的睡眠障碍的治疗作用，并探讨其可能机制。方法：采用小鼠坐骨神经部分结扎术（Partial sciatic nerve ligation，PSL）建立神经病理性疼痛小鼠模型；在此基础结合高度自动化睡眠觉醒记录与解析系统，建立神经痛性睡眠障碍小鼠模型。通过测定小鼠机械痛阈和热痛潜伏期观察普瑞巴林对PSL模型小鼠热痛敏、机械痛敏的改善作用。并通过分析睡眠时间与觉醒时间、睡眠结构、睡眠波能谱（睡眠深度）、睡眠时相转换等指标探讨普瑞巴林对PSL模型小鼠日间入睡期（07:00-11:00）睡眠障碍的改善作用；以及普瑞巴林对PSL模型小鼠和正常小鼠夜间活动期（21:00-01:00）睡眠觉醒结构的影响。利用免疫组织化学方法观察普瑞巴林对入睡期PSL模型小鼠前扣带回皮层（Anteriorcingulate cortex，ACC）c-Fos阳性神经元数量的影响。结果：①PSL模型小鼠出现持续一个月的触发痛觉过敏、热痛觉过敏以及日间入睡期睡眠障碍症状。②于09:00灌胃给予普瑞巴林（25mg/kg）使PSL模型小鼠给药后第3h机械痛阈增加3.1倍，热痛潜伏期延长59%，且不影响PSL模型小鼠Rota-rod停留时间。③于06:30灌胃给予普瑞巴林（25mg/kg）使PSL模型小鼠在入睡期（07:00-11:00）非快速动眼（non rapid eye movement，NREM）睡眠量增加40%，觉醒量减少38%；长时程NREM睡眠、快速动眼（rapid eyemovement，REM）睡眠片段数量增加；觉醒片段总数减少；NREM睡眠向觉醒转换次数减少，，NREM睡眠向REM睡眠转换次数增加。④于20:30灌胃给予普瑞巴林（25mg/kg）不影响正常小鼠和PSL模型小鼠活动期（21:00-01:00）睡眠觉醒结构。⑤于06:30灌胃给予普瑞巴林（25mg/kg）能显著降低PSL模型小鼠ACC区域c-Fos阳性神经元数量。结论：普瑞巴林对神经病理性疼痛模型小鼠具有显著的镇痛作用。普瑞巴林产生镇痛作用的同时，能有效改善痛觉诱发的睡眠障碍症状。普瑞巴林的镇痛及促眠作用可能与抑制神经病理性疼痛模型动物前扣带回皮层神经元异常性兴奋有关。
[Abstract]:Objective: neuropathic pain is a kind of pain syndrome caused directly by the injury or disease of somatosensory nervous system. PreBahrain (Pregabalin,PGB) is a kind of 纬-aminobutyric acid (Gamma-aminobutyric acid,GABA). As an epileptic drug, it has been successfully listed in Britain and America. Based on the successful establishment of animal model of neuropathic pain (partial ligation of sciatic nerve), the therapeutic effect of PreBahrain on neuropathic pain and its sleep disorder was investigated and its possible mechanism was discussed. Methods: the mouse model of neuropathic pain was established by partial ligation of sciatic nerve (Partial sciatic nerve ligation,PSL), and the model of neuropathic sleep disorder was established based on the highly automated sleep arousal recording and analysis system. By measuring the mechanical pain threshold and the latent period of heat pain in mice, the effect of Preabine on the improvement of thermal pain sensitivity and mechanical pain sensitivity in PSL model mice was observed. By analyzing sleep time and wakefulness time, sleep structure, sleep wave energy spectrum (sleep depth), sleep phase transformation, etc., the effect of Pregabin on sleep disorder in PSL model mice during daytime sleep period (07: 00-11: 00) was studied. And the effects of PreBahrain on the structure of sleep arousal in PSL model mice and normal mice during nocturnal activity (21: 00-01: 00). The effect of Premarin on the number of c-Fos positive neurons in the anterior cingulate cortex (Anteriorcingulate cortex,ACC) of PSL model mice during sleep was observed by immunohistochemical method. Results: 1PSL model mice developed a one-month trigger of hyperalgesia. The symptoms of hyperthermia and sleep disturbance during daytime sleep. (2) at 09:00, 25mg/kg was administered intragastrically to PSL model mice. The mechanical pain threshold was increased by 3.1 times, and the latent period of heat pain was prolonged by 59 times at the 3rd hour after administration of the drug in PSL model mice. The Rota-rod residence time of PSL model mice was not affected. 3 25mg/kg was given intragastric at 06:30 to increase the sleep volume of PSL model mice during the sleep period (07: 00-11: 00) non-REM (non rapid eye movement,NREM. The arousal decreased by 38. In long-term NREM sleep, the number of rapid eye movement (rapid eyemovement,REM) sleep fragments increased, and the total number of wakefulness fragments decreased. The conversion of NREM sleep to arousal decreased, The conversion of NREM sleep to REM sleep increased. 4 25mg/kg was given orally at 20:30 without affecting the awake structure of normal mice and PSL model mice during the active period (21: 00-01: 00). Gastric administration of 25mg/kg could significantly reduce the number of c-Fos positive neurons in the ACC region of PSL model mice. Conclusion: Premarin has a significant analgesic effect on neuropathic pain model mice. The analgesic effect of PreBahrain can effectively improve the symptoms of sleep disorder induced by pain. The analgesic and hypnotic effects of Premarin may be related to the inhibition of abnormal sexual excitability of cortical neurons in the anterior cingulate cortex of neuropathic pain model animals.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

【相似文献】