Key result
In a rat model of neuropathic pain, ivabradine significantly reduced mechanical allodynia with only a 15% pharmacological reduction in heart rate.
Why the study?
Does ivabradine reduce mechanical allodynia in a rat model of neuropathic pain?
Does ivabradine reduce mechanical allodynia in a rat model of neuropathic pain?
Ivabradine effectively reduces mechanical allodynia in a rat model of neuropathic pain at doses that cause only moderate heart rate reduction, suggesting potential utility in neuropathic pain management.
Ivabradine attenuates CCI-induced allodynia at tolerable doses; leaves open clinical translation for neuropathic pain.
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. 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.
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Noh et al. (2014) studied Neuropathic pain (rat chronic constriction injury model). Ivabradine was evaluated on Mechanical allodynia. In a rat model of neuropathic pain, ivabradine significantly reduced mechanical allodynia with only a 15% pharmacological reduction in heart rate.
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