Lee MC, Bond S, Wheeler D, et al. - Considering the preclinical studies demonstrating the necessity for type 2 hyperpolarization-activated cyclic nucleotide gated ion channels (HCN2) for neuropathic pain, researchers examined how ivabradine, a nonselective HCN channel blocker, influence capsaicin-induced hyperalgesia and pain in healthy human individuals. They included an enriched population comprising individuals who developed > 20 cm² of punctate hyperalgesia from topical capsaicin (0.5% cream applied onto 9 cm² area) and administered them ivabradine (15 mg) or placebo 1 hour before capsaicin application, in randomly allocated order in a crossover study. With each application of the cream, the forearm site for capsaicin alternated. Screening of 55 participants was done, of which 25 completed at least 1 treatment visit. Outcomes suggest no analgesic effects of ivabradine in the capsaicin pain model at a dose that caused appreciable slowing of heart rate and, hence, it seemed to have no value as a useful analgesic in humans. This suggests the necessity for more selective drugs to establish the role of HCN2 for pain in humans.