Premium
The heart‐rate‐reducing agent, ivabradine, reduces mechanical allodynia in a rodent model of neuropathic pain
Author(s) -
Noh S.,
Kumar N.,
Bukhanova N.,
Chen Y.,
Stemkowsi P.L.,
Smith P.A.
Publication year - 2014
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2014.00460.x
Subject(s) - ivabradine , neuropathic pain , allodynia , medicine , anesthesia , heart rate , bradycardia , dorsal root ganglion , pharmacology , hyperalgesia , nociception , blood pressure , receptor , dorsum , anatomy
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 F rey 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 I n 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. Conclusion 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.