阿米替林和氯诺昔康对神经病理性疼痛大鼠学习记忆的影响

Effects of amitriptyline and lornoxicam on learning and memory in rats with neuropathic pain

目的观察阿米替林和氯诺昔康对L5脊神经横切所致神经病理性疼痛大鼠学习记忆和海马脑源性神经营养因子(BDNF)表达的影响。方法雄性SD大鼠60只随机均分为六组:生理盐水对照组(A组)、生理盐水组(B组)、阿米替林对照组(C组)、阿米替林组(D组)、氯诺昔康对照组(E组)、氯诺昔康组(F组)。术前和术后第2、7、10、14、17、21、28天测机械痛和热痛阈值;第29天行强迫游泳实验观察抑郁行为改变;第30天行Morris水迷宫实验观察学习记忆改变。用Real-time-PCR技术和免疫组化法测定海马BDNF表达。结果与A组比较,B组大鼠术后出现显著机械痛和热痛阈值下降,静止漂浮时间延长,学习记忆能力减退,海马BDNF表达减少(P<0.01)。与B组比较,D组应用阿米替林后机械痛和热痛阈值增加,静止漂浮时间缩短,学习记忆能力提高,海马BDNF mRNA、蛋白表达增加(P<0.05或P<0.01)。与B组比较,F组应用氯诺昔康后机械痛和热痛阈值增加(P<0.05或P<0.01),但静止漂浮时间、学习记忆能力和海马BDNF表达差异无统计学意义。结论阿米替林可有效镇痛、减轻疼痛大鼠抑郁症状、改善学习记忆能力,可能与阿米替林增加海马BDNF表达有关,非疼痛减轻所致。氯诺昔康仅有镇痛效应。

Objective To investigate the effects of amitriptyline and lornoxicam on learning,memory and the expression of brain-derived neurotrophic factor（BDNF） in the hippocampus in rats with L5 spinal nerve transection-induced neuropathic pain（NP）.Methods Sixty adult male SD rats were randomly divided into 6 groups with 10 rats each of saline control group（A）,saline group（B）,amitriptyline control group（C）,amitriptyline group（D）,lornoxicam control group（E）and lornoxicam group（F）.All rats were given drugs from post-operative day 7-28.Mechanical and thermal thresholds were determined by an Electro Von Frey anesthesiometer and a paw stimulator analgesia meter.The forced swimming test assessed the depression-related behaviors on the 29th postoperative day and Morris water maze test determined the abilities of spatial learning and memory on the 30th to 35th day.Expressions of BDNF and BDNF mRNA in the hippocampus were detected by immunohistochemical methods and Real-time PCR.Results The post-operatively mechanical and thermal thresholds decreased in group B compared with those in group A（P〈0.01）.The rats in group B also experienced a longer immobility time,decreased abilities of spatial learning and memory and lower expression of hippocampal BDNF mRNA and protein than those in group A（P〈0.01）.However,the rats showed higher mechanical and thermal thresholds,a shorter immobility time,increased abilities of spatial learning and memory,higher expression of BDNF mRNA（P〈0.01） and protein（P〈0.05） in group D.The rats also displayed higher mechanical（P〈0.05） and thermal thresholds（P〈0.01）,but no significant difference was found in immobility time,abilities of spatial learning and memory and expression of BDNF in group F.Conclusion Amitriptyline could provide analgesic effects and restore the impaired abilities of spatial learning and memory via up-regulating BDNF expression in the hippocampus.Lornoxicam could only provide analgesic effects.