title: The heart-rate-reducing agent, ivabradine, reduces mechanical allodynia in a rodent model of neuropathic pain.
abstract: BACKGROUND
  Peripheral nerve injury increases the excitability of primary sensory neurons. This triggers the onset of neuropathic pain and maintains its persistence. Because changes in hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels are implicated in this process, we examined the action of the heart-rate-reducing agent, ivabradine, a clinically approved HCN blocker, in the rat chronic constriction injury (CCI) model of neuropathic pain.
  
  
  METHODS
  The effects of ivabradine on mechanical allodynia were assessed using von Frey filaments, and the effects on cardiovascular parameters were monitored by telemetry. Ivabradine block of HCN channels in dorsal root ganglion neurons was confirmed by whole-cell recording.
  
  
  RESULTS
  In rats subject to CCI, ivabradine (6 mg/kg by gavage twice a day) significantly reduced mechanical allodynia. Cumulative effects were seen with twice daily oral administration over a 4-day period. Allodynia returned 4 days after the final drug dose. Mean arterial pressure was maintained and only a 15% pharmacological reduction in heart rate was observed. There was no cumulative effect of ivabradine on cardiovascular parameters.
  
  
  CONCLUSIONS
  Because ivabradine is effective at an oral dose that produces only moderate pharmacological heart rate reduction, and this is known to be well tolerated in a clinical context, these results underline its possible use in neuropathic pain management.
authors.affiliation: Department of Pharmacology and Centre for Neuroscience, University of Alberta, Edmonton, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Noh
authors.forename: N
authors.initials: N
authors.lastname: Kumar
authors.forename: N
authors.initials: N
authors.lastname: Bukhanova
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: P L
authors.initials: PL
authors.lastname: Stemkowsi
authors.forename: P A
authors.initials: PA
authors.lastname: Smith
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000077550:Ivabradine; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D001552:Benzazepines; D000077550:Ivabradine