大鼠脊髓鞘内注射阿米洛利及混合替扎尼定治疗炎症性疼痛的研究  

Effects of Intrathecal Amiloride and Its Interaction with Tizanidine on Treatment of Inflammatory Pain in Rats

作　　者：黄婉[1] 谭红鹰[1] 欧阳汉栋[1] 畅易[1] 林丽玲[1] 张志权[1] 刘先国[2] 曾维安[1] 

机构地区：[1]华南肿瘤学国家重点实验室∥中山大学肿瘤防治中心,广东广州510060 [2]中山大学中山医学院疼痛研究中心,广东广州510089

出　　处：《中山大学学报（医学科学版）》2010年第3期376-380,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(303041102002);广东省科技计划项目(30972849)

摘　　要：【目的】评价脊髓鞘内注射阿米洛利及混合替扎尼定对炎症性疼痛的治疗效能。【方法】96只SD大鼠,质量250～300g,随机分成16组(n=6):对照组、阿米洛利组(12.5～100μg)、替扎尼定组(0.5～5μg)、混合药物组(1/2、1/4、1/8、1/16)、各拮抗组。鞘内置管后7d采用20g/L的多聚甲醛溶液50μL皮下注射方法制作炎症性疼痛模型。观察记录2时相大鼠缩足舔足次数。计算各药物的半数有效抑制剂量(ID50)及95%的可信区间。使用Isobolographic分析评价药物的相互作用。【结果】鞘内单独注射阿米洛利(12.5～100μg)和替扎尼定(0.5～5μg)可产生剂量依赖性的抗急性及慢性炎症性疼痛的作用。鞘内阿米洛利和替扎尼定混合,可以产生明显的协同效应。鞘内育亨宾预处理可以拮抗鞘内阿米洛利、替扎尼定及阿米洛利混合替扎尼定的抗炎症性疼痛的作用。【结论】鞘内单独注射阿米洛利、替扎尼定可以产生明显的剂量依赖性的抗急性及慢性炎症性疼痛的作用。鞘内注射阿米洛利可以增强替扎尼定的抗炎症性疼痛的作用。鞘内注射阿米洛利产生的抗炎症性疼痛的作用可能与中枢α-肾上腺素受体有关。【Objective】To investigate the effect of intrathecal amiloride and its interaction with tizanidine on the treatment of inflammatory pain in a rat model.【Methods】Ninety-six male SD rats（250～300 g）were randomly divided into sixteen groups（n =6）：control group;amiloride group;tizanidine group;amiloride＋tizanidine group;and yohimbine group.Seven days after IT catheter placement,50μL of 5%formalin was injected subcutaneously into the dorsal surface of the right hindpaw using 27-gauge needle.Pain-related behavior was quantified by counting the number of flinches.Inhibitory effect（ID50）values and 95% confidence intervals were calculated.Isobolographic analysis of the amiloride and tizanidine interaction was conducted.【Result】Intrathecal amiloride（12.5～100μg）or tizanidine（0.5～5μg）alone produced dose-dependent treatment effect of acute and chronical inflammatory pain.Intrathecal mixtures（tizanidine＋amiloride）produced dose-dependent treatment effect of acute and chronic inflammatory pain.Intrathecal pretreatment with yohimbine antagonized the treatment effect of amiloride,tizanidine and the combination of amiloride and tizanidine.【Conclusion】Intrathecal amiloride and tizanidine alone produced dose-dependent treatment effect of inflammatory pain.The enhancing effects were found between intrathecal amiloride and tizanidine.The treatment effect of inflammatory pain produced by intrathecal amiloride may due toα2-adrenoceptor in the spinal.

关 键 词：椎管内镇痛 炎症性疼痛 阿米洛利 替扎尼定 协同作用 

分 类 号：R614[医药卫生—麻醉学]