神经病理性痛大鼠背根神经节神经元γ氨基丁酸激活电流的改变  

Change in GABA receptor-activated current in dorsal root ganglion neurons freshly isolated from rats with neuropathic pain

作　　者：冉然[1] 姚尚龙[1] 余开峰[2] 王群[2] 王清秀[3] 顾俊峰[2] 田刚[2] 

机构地区：[1]华中科技大学同济医学院附属协和医院麻醉科,武汉市430022 [2]湖北医药学院附属人民医院麻醉科 [3]同济大学附属东方医院麻醉科

出　　处：《中华麻醉学杂志》2011年第1期55-58,共4页Chinese Journal of Anesthesiology

基　　金：十堰市科学研究与开发计划项目（2009s06）;上海市浦东新区优秀学科带头人培养计划（PWRd2007-04）

摘　　要：目的 探讨神经病理性痛大鼠背根神经节（DRG）神经元γ氨基丁酸（GABA）激活电流的改变.方法 健康成年SD大鼠20只,雌雄不拘,体重100～150g,采用随机数字表法,将大鼠随机分为2组,假手术组（S组,n=5）,神经病理性痛组（NP组,n=15）行l3脊神经结扎诱发神经病理性痛.于术后5 d处死大鼠,S组急性分离L3-5DRG神经元,NP组急性分离L5DRG神经元,建立膜片钳全细胞记录模式.通过细胞外加药排管给予GABA 100μmol/L,记录各类型DRG神经元中GABA激活电流的发生率及电流幅度,记录给GABA前、后静息电位、动作电位（基强度、阈电位和超射值）.结果 细胞外给予100μmol/L的GABA后可诱发部分神经元出现快速失活的内向电流.与给GABA前比较,S组给GABA后DRG大、中神经元出现明显去极化,静息电位升高,超射值和基强度降低（P＜0.05）,阈电位差异无统计学意义（P＞0.05）,NP组给GABA后DRG大、中神经元静息电位升高（P＜0.05）,超射值、基强度和阈电位差异无统计学意义（P＞0.05）.与S组比较,NP组DRG大、中神经元GABA激活电流的发生率和电流幅度均降低,静息电位、超射值、基强度的变化幅度降低（P＜0.05）,阈电位的变化幅度差异无统计学意义（P＞0.05）.S组和NP组部分DRG小神经元出现自发放电,具有自发放电的神经元上没有GABA激活电流出现.结论 神经病理性痛大鼠DRG大、中神经元上GABA介导的抑制信号的减弱,引起神经元兴奋性升高,可能是神经病理性痛的发病机制之一.Objective To investigate the change in GABA receptor-activated current in dorsal root ganglion （DRG） neurons in rats with neuropathic pain. Methods Twenty adult SD rats of both sexes weighing 100-150 g were randomly divided into 2 gorups： sham operation group （group S, n = 5） and neuropathic pain group （group NP, n= 15）. Neuropathic pain was induced by ligation of right L5 spinal nerve. The animals were sacrificed at 5 days after operation. The L5 DRG（ neurons in group NP and L3-5 DRG neurons in group S were immediately isolated. Whole-cellpatch- clamp technique was used. The extracellular solution contained GABA 100μmol/L.The frequency and amplitude of the GABA-activated current in DRG neurons and the changes in action potential （threshold potential, rheobase and overshoot） and resting potential before and after GABA administration were recorded. Results GABA 100μmol/L induced rapid inactivation of inward current in most neurons. Compared with the baseline before application of GABA, in group S GABA induced depolarization,increased resting potential and decreased amplitude and rheobase of action potential in large and medium DRG neurons, while in group NP GABA increased resting potential but induced no significant change in threshold potential and rheobase and overshoot of action potential. The frequency and amplitude of GABA-activated current and the degree of change in resting potential and rheobase and overshoot of action potential were significantly lower in group NP than in group S.Spontaneous discharge occurred in small DRG neurons in both groups. No GABA-activated current was observed in all DRG neurons with spontaneous discharge. Conclusions Neuropathic pain is induced by decreasing GABA-mediated inhibition signals in large and medium DRG neurons leading to increased excitability of neurons.

关 键 词：Γ氨基丁酸 神经节 脊 神经痛 

分 类 号：R741[医药卫生—神经病学与精神病学]