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

Abstract

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

CLC Number:

R965.2

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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