Introduction Hyperpolarization-activated cyclic nucleotide gated (HCN) ion channels mediate repetitive action potential firing in the heart and nervous system [1]. The HCN2 isoform is expressed in nociceptors and preclinical studies suggest a critical role in neuropathic pain [2,3]. Ivabradine is a non-selective HCN blocker that is available for prescription but licenced only for cardiac indications. Mouse data suggest that ivabradine is equianalgesic with gabapentin for neuropathic pain [3]. Aims We sought to translate these findings to patients with chronic peripheral neuropathic pain. Method The study was conducted in accordance with the spirit and the letter of the Declaration of Helsinki, the conditions and principles of International Conference on Harmonisation’s Good Clinical Practice, the protocol and applicable local regulatory requirements and laws. The study was registered prospectively (ISRCTN68734605), and ethical approval obtained from the London-Bromley Research Ethics Committee (16/LO/1901). Written informed consent was obtained from every participant before any study-related activity was performed. We adopted an open label design; administering incrementally increasing doses of ivabradine, titrating according to heart rate up to 7.5 mg twice daily. All participants gave daily pain ratings on an 11-point numerical rating scale (NRS). Results Seven participants completed the study. There was no significant treatment effect on the primary endpoint, change-from-baseline in mean NRS score (reduction = 0.878, 95% CI = -2.07 to 0.31, p=0.1). Exploratory analysis using linear mixed models revealed a highly significant but modest relationship between ivabradine dose and daily NRS pain score (c2(1)=74.6, p<0.001), with a reduction of 0.12 ± 0.01 (SEM) NRS points per mg. The two participants with painful diabetic neuropathy responded particularly well. Conclusions These preliminary data suggest there may be an analgesic effect of ivabradine at higher doses, possibly in patients with diabetic neuropathic pain. Importantly, there were no adverse effects. This suggests that ivabradine, a peripherally-restricted drug (devoid of central nervous system side effects) is well tolerated in patients with chronic neuropathic pain. Ivabradine is now off-patent and its analgesic potential merits further investigation in clinical trials.