Brief Article
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World J Gastroenterol. Feb 28, 2014; 20(8): 2091-2097
Published online Feb 28, 2014. doi: 10.3748/wjg.v20.i8.2091
ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable bowel syndrome-like rats
Yu Chen, Chun Lin, Ying Tang, Ai-Qin Chen, Cui-Ying Liu, Da-Li Lu
Yu Chen, Chun Lin, Ying Tang, Ai-Qin Chen, Cui-Ying Liu, Da-Li Lu, Laboratory for Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Center for Neuroscience Research, Department of Physiology and Pathophysiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
Author contributions: Lin C designed the research; Chen Y, Tang Y, Liu CY and Lu DL performed the experiments; Chen AQ and Lu DL analyzed the data; Chen Y and Lin C wrote the manuscript.
Supported by The Natural Science Fund of Fujian Province, No. C0910595 and No. 2012J05053; Science Fund and Doctor Initial Fund of FMU, No. 09ZD009 and No. 2010BS008
Correspondence to: Chun Lin, MD, Professor, Chief, Laboratory for Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Center for Neuroscience Research, Department of Physiology and Pathophysiology, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou 350108, Fujian Province, China. chunlin77550@126.com
Telephone: +86-591-22862439 Fax: +86-591-22862439
Received: August 19, 2013
Revised: December 7, 2013
Accepted: January 8, 2014
Published online: February 28, 2014
Processing time: 190 Days and 18.6 Hours
Abstract

AIM: To investigate the effects of ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on rats with chronic visceral pain.

METHODS: Rats with visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously. Visceral hypersensitivity was evaluated using electromyographic (EMG) responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions (CRD). Abdominal withdrawal reflex (AWR) scores and pain thresholds were also detected in adult rats. Different doses of ZD 7288 (25, 50, and 100 nmol/L) were intrathecally administered in rats to study the role of spinal HCN channel in chronic visceral hypersensitivity.

RESULTS: EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral hypersensitivity compared to control rats (P < 0.05). The pain threshold in rats with visceral hypersensitivity significantly decreased compared to control rats (P < 0.05). Treatment with 50-100 nmol/L ZD 7288 significantly inhibited EMG responses (16%-62%, 80-20 mmHg CRD, P < 0.05) and AWR scores (24%-37%, 40-20 mmHg CRD, P < 0.05; 12%-61%, 80-20 mmHg CRD, P < 0.05, respectively), and significantly increased pain thresholds (32%-77%, P < 0.05).

CONCLUSION: Spinal HCN channels may play an important role in chronic visceral hypersensitivity.

Keywords: Abdominal withdrawal reflex; Electromyography; Hyperpolarization-activated cyclic nucleotide-gated channel; Visceral hypersensitivity; ZD 7288; Irritable bowel syndrome

Core tip: Intrathecal administration of ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated channel blocker, significantly inhibited electromyographic responses and abdominal withdrawal reflex scores and significantly increased pain thresholds in rats with chronic visceral hypersensitivity. These results are important for clinicians and the fundamental scientific community and provide scientific evidence for ZD 7288 as a novel treatment for visceral pain in irritable bowel syndrome.