神经病理性疼痛对大鼠学习记忆功能和海马脑源性神经营养因子表达的影响

Neuropathic pain impairs spatial learning and memory and reduces BDNF mRNA expression in the hippocampus of rats

目的：临床研究发现慢性疼痛患者常伴反焦虑、抑郁等疾病,而焦虑抑郁易导致认知功能障碍。然而神经病理性疼痛对认知功能的影响尚不清楚。观察L5脊神经结扎横切（L5-SNT）所致神经病理性疼痛（NP）对成年大鼠学习记忆功能和海马脑源性神经营养因子（BDNF）mRNA表达的影响,探讨NP对成年大鼠空间学习记忆能力的影响及可能的作用机制。方法：成年SD大鼠24只,随机分为疼痛组和对照组（n=12）。疼痛组施行左侧L5-SNT手术,对照组行假手术即仅暴露L5脊神经不结扎。分别于术前和术后第2、7、14、21、28 d测机械痛阈和热痛阈。术后第29 d进行Morris水迷宫实验测量大鼠空间学习记忆能力。水迷宫实验结束后,采用Real-time PCR技术检测海马BDNF mRNA表达的变化。结果：术前2组机械痛阈和热痛阈无显著差异,术后疼痛组2~28 d各时间点与对照组相比,机械痛阈和热痛阈均降低（P〈0.01）。Morris水迷宫实验中,疼痛组大鼠寻找隐藏平台潜伏期较对照组延长（P〈0.01）,并且在平台所在象限的游泳时间和路径与总游泳时间和路径的比例均小于对照组（P〈0.01）。疼痛组大鼠海马BDNF mRNA表达低于对照组（P〈0.01）。结论：L5-SNT引起的NP可导致成年大鼠空间学习记忆能力减退,其机制可能与海马BDNF表达改变有关。

Objective： Clinical studies have shown that patients with chronic pain are more likely to have anxiety and depression,which are often associated with cognitive dysfunction.However,whether neuropathic pain may induce cognitive dysfunction remains uncertain.The present study aimed to investigate the effects and possible mechanisms of L5 spinal nerve transection induced neuropathic pain on spatial learning and memory ability and the expression of hippocampal BDNF mRNA in adult rats.Methods： Twenty-four Sprague-Dawley rats were randomly divided into a pain group（n = 12） and a control group（n = 12）,the former given left L5 spinal nerve transection,and the latter sham operation.Mechanical allodynia and thermal hyperalgesia were evaluated on postoperative day 0,2,7,14,21 and 28 by Von Frey and Hargreaves tests.The performance of spatial learning and memory of all the rats was measured using the Morris water maze test on day 29,and the expression of BDNF mRNA in the hippocampus was detected by Real-time PCR.Results： There was no significant difference in mechanical and thermal thresholds between the two groups before operation（P 〉 0.05）.Compared with the controls,the rats in the pain group displayed marked mechanical allodynia and thermal hyperalgesia up to day 28 after operation（P 〈 0.01）,a longer mean escape latency in the hidden platform training of Morris water maze（P 〈 0.01）,smaller average percentages of swimming time and distance in the platform quadrant in the spatial probe test（P 〈 0.01）,and a lower level of BDNF mRNA in the hippocampus.Conclusion： L5 spinal nerve transection induced neuropathic pain could impair the spatial learning and memory function in adult rats by down-regulating the BDNF mRNA expression in the hippocampus.