慢性神经痛对中脑腹侧被盖区多巴胺神经元活动水平的影响  

THE IMPACT ON ELECTROPHYSIOLOGY ACTIVITY LEVEL OF DOPAMINERGIC NEURONS IN THE VENTRAL TEGMENTAL REGION OF THE MIDBRAIN BY CHRONIC NEUROPATHIC PAIN

作　　者：李永丰[1] 钱召强[2] LI Yong-Feng;QIAN Zhao-Qiang(MOE Key Laboratory of Modern Teaching Technology,Shanxi Normal University,Xi＇an 710062,China;College of life science,Shanxi Normal University,Xi＇an 710062,China)

机构地区：[1]陕西师范大学现代教学技术教育部重点实验室,西安710062 [2]陕西师范大学生命科学学院,西安710062

出　　处：《中国疼痛医学杂志》2018年第11期815-822,共8页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金项目(81771227)

摘　　要：目的:探讨小鼠慢性疼痛发生过程中,中脑腹侧被盖区(ventral tegmental area, VTA)多巴胺神经元自发放电活动的变化情况。方法:64只健康成年小鼠进行随机分为2组;假手术组(Sham)只暴露出坐骨神经不结扎,坐骨神经慢性压迫组(chronic constriction injury, CCI)分离肌肉暴露坐骨神经主干,用鼠尾胶原纤维(约5#羊肠线直径)从坐骨神经中枢端到外周端依次减轻结扎力度,打三个结进行损伤。在手术前1天和术后第4、7、14、21、30天进行机械和热刺激计算缩足反射阈值,并进行糖水偏爱、旷场、高架十字迷宫等行为学实验来评价小鼠的情绪变化;利用在体多通道电生理技术,对CCI组小鼠中脑腹侧被盖区多巴胺神经元进行记录分析。结果:与假手术组比较,CCI组小鼠的机械和热痛阈值明显降低(P <0.01);术后检测糖水偏爱测试(第33天)、旷场测试(第35天)、高架十字迷宫测试(第35天)较术前出现显著性差异(P <0.01);小鼠中脑腹侧被盖区多巴胺能神经元自发放电频率、簇状放电活动中动作电位的数量在第14天明显增加,第35天显著降低(P <0.01)。结论:慢性疼痛经历后可以导致小鼠焦虑、抑郁样情绪的发生,中脑腹侧被盖区多巴胺能神经元活动与疼痛经历导致的焦虑抑郁样情绪发生相关。Objective： To investigate the spontaneous discharge of ventral tegmental area（VTA） dopamine neurons in the process of neuropathic pain. Methods： Sixty-four C57 BL/6 J mice were randomly divided into Sham and CCI groups. In the sham operation group, the sciatic nerve of the mice was exposed without ligature. In the sciatic nerve chronic group（Chronic Constriction Injury, CCI）, the main trunk of the sciatic nerve was isolated, and the sciatic nerve was ligated from the sciatic nerve center to the peripheral end using the rat tail collagen fiber. The strength of the ligation is light, and three knots were made. The mechanical withdrawal threshold（MWT） and thermal withdrawal latency（TWL） were detected at 1 day before surgery and 4, 7, 11, 14, 21, 30 days after surgery. The depression and anxiety behaviors were tested by sucrose preference test, the open field test, and elevated plus maze test. The multichannel acquisition processor neurophysiology system was used to record and analyze the firing activity of VTA dopaminergic neurons. Results： Compared to Sham group, the pain threshold in CCI group was remarkably decreased（P 〈0.01）. The sucrose preference, the time spent in the center of open field, the time spent and the entries in the open arm of elevated plus maze were decreased. The VTA dopamine neurons fire frequency and the number of burst were significantly increased on Day 14, but reduced on Day 35 after surgery. Conclusion： The neuropathic pain can induce anxiety and depression in mice, and the changes of the spontaneous discharge of VTA dopamine neurons may have a correlation with the electrophysiological mechanism for anxiety and depression.

关 键 词：焦虑抑郁样情绪 多巴胺能神经元 慢性痛 自发放电 小鼠 

分 类 号：R402[医药卫生—临床医学]