胍丁胺抑制炎性疼痛诱导脊髓磷酸化细胞外信号调节激酶表达上调

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (9): 1018-1022.

胍丁胺抑制炎性疼痛诱导脊髓磷酸化细胞外信号调节激酶表达上调

秦晓辉¹, 吴宁², 苏瑞斌², 张宏¹, 李锦²

¹中国人民解放军总医院麻醉科, 北京100853;
²军事医学科学院毒物药物研究所, 北京100850

收稿日期:2006-08-11 修回日期:2006-09-21 出版日期:2007-09-26 发布日期:2020-10-30
通讯作者: 李锦, 男, 教授, 博士生导师, 研究方向:神经精神药理和新药评价。Tel:010-66931603 E-mail:jinli9802@yahoo.com
作者简介:秦晓辉, 女, 博士, 主治医师, 主要从事麻醉与疼痛机理方面的研究。Tel:010-66937342 E-mail:qxh301@126.com
基金资助:
国家重点基础研究发展计划(973 计划) 资助项目(2003CB515400);中国高技术研究发展计划(863 计划)资助项目(2002AA2Z3028)

Agmatine inhibits inflammatory pain induced phosphorylated extracellular signal-regulated protein kinase up-regulation in spinal dorsal horn

QIN Xiao-hui¹, WU Ning², SU Rui-bin², ZHANG Hong¹, LI Jin²

¹Department of Anesthesiology, Chinese PLAGeneral Hospital, Beijing 100853, China;
²Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

Received:2006-08-11 Revised:2006-09-21 Online:2007-09-26 Published:2020-10-30

摘要/Abstract

摘要： 目的:观察胍丁胺对福尔马林致炎性疼痛的镇痛作用, 并研究其镇痛作用是否与影响脊髓磷酸化细胞外信号调节激酶(phosphorylated extracellularsignal-regulated protein kinase, pERK) 表达有关。方法:雄性SD 大鼠, 180～220 g, 随机分为生理盐水对照组、福尔马林组和胍丁胺160 mg/kg 组, 每组20只。每组12 只右侧足底皮下注射5%的福尔马林50 μL 致痛, 每5 min 为一个时间段, 测定60 min 内大鼠的痛级均数。另外每组8 只足底注射福尔马林后8 min 取L_4,5脊髓, 用免疫组化法检测各组脊髓切片中pERK 的表达情况。结果:大鼠单侧足底注射5%福尔马林50 μL 后出现明显的两期伤害性行为反应。胍丁胺对福尔马林引起的疼痛反应有明显的镇痛作用, 且能抑制福尔马林引起的痛觉过敏。福尔马林对大鼠单侧足底注射8 min 后, 引起注射侧L_4,5脊髓背角pERK 表达量升高, 160 mg/kg 胍丁胺(i.p.) 明显抑制福尔马林引起的pERK 表达量的升高。结论:胍丁胺对福尔马林引起的疼痛及痛觉过敏行为有明确的抑制作用, 炎性疼痛引起脊髓pERK蛋白表达升高可能参与疼痛及痛觉过敏的形成,pERK 可能参与了胍丁胺镇痛机制。

关键词: 胍丁胺, 疼痛, 痛觉过敏, 磷酸化细胞外信号调节激酶

Abstract: AIM: To evaluate the analgesic effect of agmatine on the model of formalin-evoked nociception;To investigate the changes in the expression of phosphorylated extracellular signal-regulated protein kinase (pERK) in the spinal dorsal horn of the formalin-induced inflammatory pain and the effect of agmatine on the pERK expression.METHODS: Male SD rats weighing 180-220 g were randomly classified into saline control group, formalin group, and agmatine group n=20.Rats were injected subcutaneously with 50 μL of 5% formalin solution into the plantar surface of the right hind paw.During the next 60 min, the weighted pain score was recorded in 5-min intervals for 12 rats group.Another 8 rats group were decapitated at 8 min after intraplantar injection and L_4,5 spinal cords were dissected and coronal sections were cut. Immunohistochemistry was used to observe the changes of pERK expression in the dorsal horn of spinal cord.RESULTS: Intraplantar injection of formalin produced a typical biphasic nociceptive response.Intraperitoneally pretreatment with agmatine inhibited the nociceptive and hyperalgesic response.Injection of 5% formalin subcutaneously in the hindpaw of rats induced an increase in pERK expression in neurons in the superficial dorsal horn on the ipsilateral side of the L_4,5 spinal cord.Pretreatment with 160 mg/kg agmatine significantly inhibited formalin-induced spinal pERK expression.CONCLUSION :Agmatine induces analgesia in the formalin-induced nociception.pERK activation may underlie spinal nociceptive processing and secondary hyperalgesia after formalin inflammation and may contribute to the analgesic effects of agmatine.

Key words: agmatine, analgesia, hyperalgesia, phosphorylated extracellular signal-regulated protein kinase

中图分类号:

R965.2

秦晓辉, 吴宁, 苏瑞斌, 张宏, 李锦. 胍丁胺抑制炎性疼痛诱导脊髓磷酸化细胞外信号调节激酶表达上调[J]. 中国临床药理学与治疗学, 2007, 12(9): 1018-1022.

QIN Xiao-hui, WU Ning, SU Rui-bin, ZHANG Hong, LI Jin. Agmatine inhibits inflammatory pain induced phosphorylated extracellular signal-regulated protein kinase up-regulation in spinal dorsal horn[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(9): 1018-1022.

参考文献

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