ZD7288抑制急性内脏痛大鼠痛觉敏化

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (7): 721-726.

• 基础研究 • 下一篇

ZD7288抑制急性内脏痛大鼠痛觉敏化

黄扬, 唐影, 刘宾, 鲍成佳, 林春

福建医科大学基础医学院,疼痛研究室,福州 350108,福建

收稿日期:2014-04-09 修回日期:2014-06-19 发布日期:2014-07-21
通讯作者: 林春,女,博士,教授,硕导,研究方向:慢性内脏痛机制。Tel: 0591?22862439 　E?mail: chunlin77550@126.com
作者简介:黄扬,女,硕士,副教授,研究方向:慢性内脏痛机制、肿瘤病理。
基金资助:
福建省教育厅科学基金(JA10136); 福建省自然科学基金(2014J01124)

Inhibitory effect of ZD7288 on visceral hypersensitivity in rats with acute visceral pain

HUANG Yang, TANG Ying, LIU Bin, BAO Cheng-jia, LIN Chun

School of Basic Medical Science, Lab of Pain Research, Fujian Medical University, Fuzhou 350004, Fujian, China

Received:2014-04-09 Revised:2014-06-19 Published:2014-07-21

摘要/Abstract

摘要： 目的观察超极化激活环核苷酸门控阳离子通道(HCN通道)的特异性阻断剂ZD7288对急性内脏痛大鼠痛觉敏化的影响。方法选用成年雄性SD大鼠,通过结肠内注射1% 醋酸 1 mL,建立急性内脏痛模型;免疫组织化学法检测HCN2在模型大鼠腰骶段背根神经节及胸腰段与腰骶段脊髓背角的表达;通过腹壁撤退反射评分和腹外斜肌放电测量,观察模型大鼠鞘内分别给予50与 100 nmol/L ZD7288后内脏痛觉敏化是否发生改变。结果 HCN2在模型大鼠腰骶段背根神经节及胸腰段与腰骶段脊髓背角的表达均较对照大鼠增强(P<0.05)。鞘内注射50~100 nmol/L ZD7288可以剂量依赖性降低急性内脏痛模型大鼠的腹壁撤退反射评分和腹外斜肌放电幅值(P<0.05)。结论 ZD7288可抑制急性内脏痛大鼠的痛觉敏化,而背根神经节和脊髓的HCN2通道可能在其发病中起作用。

关键词: 内脏痛, 背根神经节, 脊髓, ZD7288, 超极化激活环核苷酸门控阳离子通道

Abstract: AIM: Effects of ZD7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on visceral hypersensitivity were investigated in rats with acute visceral pain. METHODS: SD male rats with acute visceral pain were established by injection of 1% acetic acid 1 mL into the colons. The expression and distribution of HCN2 channel protein at dorsal root ganglion, thoracolumbar and lumbosacral spinal cord were detected using immuno-histochemical techniques in control and model rats. Meanwhile, effects of 50 and 100 nmol/L ZD7288 (i.p.) on visceral hypersensitivity were tested by means of abdominal withdrawal reflex (AWR) and electromyographic (EMG) responses of abdominal external oblique muscles to 20-80 mmHg colorectal distention. RESULTS:Expressions of HCN2 channel protein at dorsal root ganglion, thoracolumbar and lumbosacral spinal cord were significantly increased in rats with acute visceral pain than those in control rats(P<0.05). And intrathecal administration of ZD7288 significantly reduced visceral hypersensitivity in a dose-dependent manner in rats with acute visceral pain(P<0.05). CONCLUSION: ZD7288 could inhibit visceral hypersensitivity in rats with acute visceral pain, and HCN2 channels at dorsal root ganglion and spinal cord may play an important role in acute visceral pain.

Key words: visceral pain, dorsal root ganglion, spinal cord, ZD7288, hyperpolarization-activated cyclic nucleotide-gated channel

中图分类号:

R965.2

黄扬, 唐影, 刘宾, 鲍成佳, 林春. ZD7288抑制急性内脏痛大鼠痛觉敏化[J]. 中国临床药理学与治疗学, 2014, 19(7): 721-726.

HUANG Yang, TANG Ying, LIU Bin, BAO Cheng-jia, LIN Chun. Inhibitory effect of ZD7288 on visceral hypersensitivity in rats with acute visceral pain[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(7): 721-726.

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ZD7288抑制急性内脏痛大鼠痛觉敏化

Inhibitory effect of ZD7288 on visceral hypersensitivity in rats with acute visceral pain

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