title: ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable bowel syndrome-like rats.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Spinal HCN channels may play an important role in chronic visceral hypersensitivity.
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Chun
authors.initials: C
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Ai-Qin
authors.initials: AQ
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Cui-Ying
authors.initials: CY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Da-Li
authors.initials: DL
authors.lastname: Lu
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D059350:Chronic Pain; D003106:Colon / Q000473:pathology; D004195:Disease Models, Animal; D004576:Electromyography; D006930:Hyperalgesia; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D010146:Pain / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059265:Visceral Pain / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D002316:Cardiotonic Agents; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D011743:Pyrimidines; C082246:ICI D2788
keywords: Abdominal withdrawal reflex; Electromyography; Hyperpolarization-activated cyclic nucleotide-gated channel; Irritable bowel syndrome; Visceral hypersensitivity; ZD 7288