ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable bowel syndrome-like rats.

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.

• Authors: Yu Chen, Chun Lin, Ying Tang, Ai-Qin Chen, Cui-Ying Liu, Da-Li Lu
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 8 Pg. 2091-7 (Feb 28 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 24587682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Cardiotonic Agents
• Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
• Pyrimidines
• ICI D2788

Topics

• Analgesics (pharmacology)
• Animals
• Cardiotonic Agents (therapeutic use)
• Chronic Pain
• Colon (pathology)
• Disease Models, Animal
• Electromyography
• Hyperalgesia
• Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (antagonists & inhibitors)
• Irritable Bowel Syndrome (drug therapy)
• Male
• Muscle, Skeletal (pathology)
• Pain (drug therapy)
• Pain Threshold (drug effects)
• Pyrimidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Visceral Pain (drug therapy)