鞘内注射不同剂量2-PMPA对切口痛大鼠的镇痛作用研究  

THE ANALGESIC EFFECTS OF DIFFERENT DOSES OF INTRATHECAL 2-PMPA ON INCISION PAIN IN RATS

作　　者：张苏明[1] 李莉[1] 王存金[1] 庞君[1] 张励才[1] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,江苏省麻醉与镇痛应用技术重点实验室

出　　处：《中国疼痛医学杂志》2014年第3期135-138,共4页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金(81371243);江苏省自然科学基金(BK2012580)

摘　　要：目的：研究蛛网膜下腔注射不同剂量NAAG肽酶抑制剂2-磷酸甲基戊二酸[2-（Phosphonomethyl）-pentanedioic acid,2-PMPA]对切口痛大鼠的镇痛作用.方法：雄性SD大鼠30只,随机分为切口痛模型组（A组）、2-PMPA治疗组（B组）和第Ⅱ组代谢型谷氨酸受体拮抗剂（LY-341495）组（C组）,B组又根据2-PMPA剂量的不同分为B1组（10 μg）、B2组（50 μg）和B3组（100 μg）.所有大鼠于左后爪作一纵形切口制备切口痛模型,术后A组鞘内注射5％ DMSO溶剂10 μl;B组鞘内注射不同剂量的2-PMPA;C组鞘内注射100 μg 2-PMPA,于注射前30min腹腔注射LY-341495 1mg/kg.术后2h以累积疼痛评分（calculative pain score,CPS）和机械缩足阈值（paw withdrawal threshold,PWT）评估疼痛强度.结果：A组、B1组、B2组、B3组和C组大鼠术前的CPS和PWT值均无显著性差异,与术前相比,术后各组的CPS（14.17±2.18）、（13.50±1.87）、（9.17±1.67）、（4.83±1.47）、（12.68±1.98）均升高（P＜0.05）,PWT值（3.13±1.36）、（4.07±1.44）、（9.40±2.61）、（15.83±6.74）、（4.26±2.06）均降低（P＜0.05）.术后A组与B1组的CPS和PWT值相比均无显著性差异（P＞0.05）;B2组和B3组与A组和B1组相比术后CPS均降低,PWT值均升高,差异有统计学意义（P＜0.05）;B3组与B2组相比术后CPS降低,PWT值升高,差异有统计学意义（P＜0.05）;C组与B3组相比术后CPS升高,PWT值降低,差异有统计学意义（P＜0.01）.结论：NAAG肽酶抑制剂2-PMPA对切口痛大鼠有明显镇痛作用,且随剂量增大而增强,其镇痛作用与提高细胞外NAAG水平进而激活第Ⅱ组代谢型谷氨酸受体有关.Objective：To investigate the analgesic effects of different doses of intrathecal 2-（Phosphonomethyl）-pentanedioic acid （2-PMPA） on a rat model of incision pain.Methods：Thirty adult male Sprague-Dawley rats were randomly divided into incision pain model group （group A）,2-PMPA treatment group （group B） and group Ⅱ metabotropic glutamate receptors antagonist （LY-341495） group （group C）.Based on the different doses,group B was divided into three subgroups：group B1 （10 μg）,group B2 （50 μg） and group B3 （100 μg）.Longitudinal incision was performed in the left hindpaw to establish pain model.After the surgery rats in group A were given 5％ DMSO solvent at the dose of 10 μl.Group B were given different doses of 2-PMPA intrathecally.Group C were given intraperitoneal injection of 1 mg/kg LY-341495 followed 30min later by intrathecal injection of 100 μg 2-PMPA.The cumulative pain score （CPS） and paw withdrawal threshold （PWT） were measured in each group to evaluate the pain magnitude at 2 h after incision.Results：There were no significant differences in CPS and PWT between group A,B1,B2,B3 and C before operation.Compared with baseline,the CPS in each group （14.17± 2.18）,（13.50± 1.87）,（9.17 ± 1.67）,（4.83 ± 1.47）,（12.68± 1.98） was significantly increased and PWT （3.13 ± 1.36）,（4.07±1.44）,（9.40±2.61）,（15.83±6.74）,（4.26±2.06） was significantly decreased after operation （P ＜ 0.05）.There were no significant differences in CPS and PWT between group A and B 1 after operation （P ＞ 0.05）.The CPS and PWT in group B2 and B3 were significantly lower and the PWT were significantly higher than group Aand B1 after operation （P ＜ 0.05）.The CPS in group B3 were significantly lower and PWT were significantly higher than group B2 after operation （P ＜0.05）.The CPS in group C were significantly higher and PWT were significantly lower than group B3 after operation （P ＜ 0.01）.Conclusion：NAAG peptidase inhib

关 键 词：2-PMPA 切口痛 NAAG肽酶抑制剂 第Ⅱ组代谢型谷氨酸受体 

分 类 号：R96[医药卫生—药理学]