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大鼠鞘内阿米洛利及混合可乐定对神经病理性疼痛的作用

Effects of Intrathecal Amiloride and Its Interaction with Clonidine on Treatment of Neuropathic Pain in Rats

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【作者】 陈祥楠; 邢蔚; 曾维安; 欧阳汉栋; 李强; 王培宗; 刘先国;

【Author】 CHEN Xiang-nan1,2, XING Wei1, ZENG Wei-an1, OUYANG Han-dong1, LI Qiang1, WANG Pei-zong1, LIU Xian-guo3(1. State Key Laboratory of Oncology in Southern China∥Cancer Center, SUN Yat-sen University, Guangzhou 510060; 2.Guangdong Women and Children’s Hospital and Health Institute, Guangzhou 510010; 3. Pain Research Center, Zhongshan School of Medicine, SUN Yat-sen University, Guangzhou 510089, China)

【机构】 华南肿瘤重点实验室∥中山大学肿瘤防治中心; 中山大学中山医学院疼痛研究中心 广东广州510060广东省妇幼保健院; 广东广州510010; 广东广州510060; 广东广州510089;

【摘要】 【目的】探讨大鼠鞘内阿米洛利及混合可乐定对神经病理性疼痛的治疗效能。【方法】102只SD大鼠,体质量(250~300g),随机分成17组(n=6):对照组、阿米洛利组、可乐定组、混合药物组、拮抗组等。鞘内置管后7d制作大鼠神经病理性疼痛模型(SNL模型)。建立疼痛模型前(基础值)、建立疼痛模型后1,3,5,7d及鞘内给药后测定大鼠机械性缩足反应阈值。计算各药物的半数有效剂量(ED50)及95%的可信区间。使用Isobolographic评价药物的相互作用。【结果】鞘内单独注射阿米洛利(12.5~100μg)或可乐定(0.5~10μg)可产生时间、剂量依赖性的抗神经病理性疼痛的作用(P<0.05);鞘内阿米洛利和可乐定混合,可以产生明显的协同效应;鞘内育亨宾(20μg)预处理可以拮抗鞘内阿米洛利、可乐定及阿米洛利混合可乐定的抗神经病理性疼痛的作用(P<0.05)。【结论】鞘内单独注射阿米洛利、可乐定可以产生明显的时间、剂量依赖性的抗神经病理性疼痛的作用;鞘内注射阿米洛利可以增强可乐定的抗神经病理性疼痛的作用。

【Abstract】 [Objective] To investigate the effects of intrathecal amiloride and its interaction with clonidine on the treatment of neuropathic pain in a rat model. [Methods] One hundred and two male SD rats weighing 250~300 g were randomly divided into seventeen groups (n=6): control group; amiloride group; clonidine group; amiloride + clonidine group, and yohimbine group (amiloride + clonidine + yohimbine). Seven days after intrathecal catheter placement, neuropathic pain model (spinal nerve ligation, SNL model) rats were developed. Paw withdrawal threshold were measured before SNL (baseline), 1, 3, 5, and 7 days after SNL and after intrathecal drug treatment. Median effective dose (ED50) values and 95% confidence intervals were calculated. Isobolographic analysis of the amiloride and clonidine interaction was conducted. [Result] Intrathecal amiloride (12.5~100 μg) or clonidine (0.5~10 μg) alone produced a time- and dose-dependent treatment effect of neuropathic pain(P < 0.05). The enhancing effects were found between intrathecal amiloride and clonidine. Intrathecal pretreatment with yohimbine (20 μg) antagonized the treatment effects of amiloride, clonidine and the combination of amiloride and clonidine(P < 0.05). [Conclusion] Intathecal amiloride and clonidine alone produced a time- and dose-dependent treatment effects on neuropathic pain.The enhancing effects were found between intrathecal amiloride and clonidine.

【基金】 国家自然科学基金(30571794);国家自然科学基金(C03030301)
  • 【文献出处】 中山大学学报(医学科学版) ,Journal of Sun Yat-Sen University(Medical Sciences) , 编辑部邮箱 ,2008年03期
  • 【分类号】R96
  • 【被引频次】5
  • 【下载频次】237
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