脊髓多巴胺D2受体在度洛西汀抑制大鼠神经病理性疼痛中的作用  

Role of spinal dopamine Dz receptors in analgesic effect of duloxetine in rats with neuropathic pain

作　　者：陈觅 杨扬 邹小华 吴宇明 吴金丽 胡廷菊 曾祥刚 Chen Mi;Yang Yang;Zou Xiaohua;Wu Yuming;Wu Jinli;Hu Tingju;Zeng Xianggang(Department of Anesthesiology,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China（Chen M,Yong Y,Zou XH,Wu JL,Hu TJ,Zeng XG;School of Anesthesiology,Guizhou Medical University,Guiyang 550004,China（Wu YM)

机构地区：[1]贵州医科大学附属医院麻醉科,贵阳550004 [2]贵州医科大学麻醉学院,贵阳550004

出　　处：《国际麻醉学与复苏杂志》2018年第9期814-818,共5页International Journal of Anesthesiology and Resuscitation

基　　金：中国心胸血管麻醉学会疼痛学分会新晨杯西部优秀青年麻醉医师培育项目基金（CSCVA-PM-2017003）

摘　　要：目的评价度洛西汀抑制大鼠神经病理性疼痛的作用以及脊髓多巴胺D2受体在其中的作用。方法实验Ⅰ，健康雄性SD大鼠24只，体重200～250g，采用随机数字表法分为4组（每组6只）：二甲基亚砜（dimethyl sulfoxide，DMSO）组（DS组）、度洛西汀3mg／kg组（D1组）、度洛西汀10mg／kg组（D2组）、度洛西汀30mg／kg组（D3组）。L5脊神经结扎（spinal nerve ligation，SNL）14d后腹腔注药，于SNL术前（T0）、注药前（T1）、注药后15min（T2）、注药后30min（T3）、注药后60min（T4）、注药后120min（T5）、注药后180min（T6）时测定大鼠术侧后足机械刺激缩足反射阈值（mechanical withdrawal threshold，MWT）。实验Ⅱ，健康雄性SD大鼠，体重200～250g，取SNL7d后行鞘内置管成功的大鼠24只，采用随机数字表法分为4组（每组6只）：DMSO＋DMSO组（DS＋DS组）、舒必利＋DMSO组（Sul＋DS组）、DMSO＋度洛西汀组（DS＋Dul组）、舒必利＋度洛西汀组（Sul＋Dul组）。鞘内置管7d后腹腔注药，于T0、T1、T2、L3、T4、T5、T6时测定大鼠术侧后足MWT。实验Ⅲ，健康雄性SD大鼠12只，体重200—250g，采用随机数字法分为2组（每组6只）：DMSO组（N组）和度洛西汀组（D组）。L3～L6脊髓行微透析，于腹腔注药前（T7）、注药后30min（T8）、注药后60min（T9）、注药后90min（T10）、注药后120min（T11）、注药后150min（T12）、注药后180min（T13）时用高效液相色谱法测定透析液的多巴胺浓度，记录多巴胺浓度和平衡透析液浓度的百分比。结果与DS组比较，D3组T2-T6时MWT升高（P〈0．05）；与DS＋Dul组比较，Sul＋Dul组T2～T6时MWT降低（P〈0．05）；与N组比较，D组T8-T13时多巴胺浓度与平衡透析液浓度比值明显升高（P〈0．05）。结论度洛西汀可抑制大鼠神经病理性疼痛，其机制可能与脊髓多巴胺D2受体有关。Objective To evaluate the involvement of spinal dopamine D2 receptors in the analgesic effect of duloxetine in neuropathic pain rat models. Methods Experiment Ⅰ, twenty-four male SD rats, weighting 200-250 g, were randomly divided into 4 groups （n=6）, respectively receiving intraperitoneal injection of dimethyl sulfoxide （DMSO） （group DS）, 3 mg/kg duloxetine （group DI）, 10 mg/kg duloxetine （group D2）, and 30 mg/kg duloxetine （group D3）. These treatments started 7 days after spinal L5 nerve ligation, and the mechanical withdraw threshold （MWT） was determined at 7 time points： before spinal nerve ligation （SNL） surgery （T0）, before duloxetine injection （T0, and 15 min （T2）, 30 min （T3）, 60 min （T4）, 120 min （T5）, 180 min （T6） after duloxetine injection. Experiment Ⅱ, twenty-four male SD rats, weighting 200-250 g, were subjected to intrathecal catheters insertion, and were randomly divided into 4 groups （n=6）. In group DS, DMSO （group DS＋DS） or 30 Ixg sulpride （group Sul＋DS） was administered intrathecally 15 min before DMSO intraperitoneal injection. In group Dul, DMSO （group DS ＋Dul） or 30 μg sulpride （group Sul ＋Dul） was administered intrathecally 15 min before 30 mg/kg duloxetine intraperitoneal injection. Mechanical paw withdraw threshold was determined before and after duloxetine or DMSO injection. Experiment Ⅲ, twelve male SD rats, weighting 200-250 g, were randomly divided into 2 groups （n=6）, respectively receiving intraperitoneal injection of DMSO （group N） and 10 mg/kg duloxetine （group D）. Then, the concentrations of dopamine in the spinal cord were measured with microdialysis before and after injection of duloxetine or DMSO injection. Results Compared with group DS, the MWT was significantly increased in group D3 at T2-T6 （P〈0.05）. Compared with group DS＋Dul, the MWT was dramatically decreased in group Sul＋Dul at T2-T6 （P〈0.05）. Compared with group N, the concentrations of dopamine i

关 键 词：神经病理性疼痛 度洛西汀 脊髓背角 多巴胺D2受体 

分 类 号：R741[医药卫生—神经病学与精神病学]