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

• 基础研究 • 上一篇    下一篇

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. 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   

  1. 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: 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L4,5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L4,5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 L4,5 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 L4,5 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

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