Weyer-Menkhoff I, et al. - As among TRP ion channels, TRPM8 and TRPA1 have received particular interest with respect to their role in human cold nociception and as analgesic drug targets, researchers here examined the local expression of 2 types of ion channels (TRPM8 vs TRPA1 ion channels) in epidermal nerve fibers. They observed the correlation of the density at epidermal nerve fibers of TRPM8, but not of TRPA1 expression, with the cold pain threshold in 28 individuals exhibiting either high or medium sensitivity to local cooling of the skin. Moreover, based on high or medium sensitivity to cooling, a reproducible grouping of the individuals was exhibited in an analogous grouping based on high or low TRPM8 expression at epidermal nerve fibers. This study reproduced the previously observed (bi)modal distribution of human cold pain thresholds; a possible explanation for this is provided by the distribution of TRPM8 expression in epidermal nerve fibers. Considering the current controversies on the role of human TRPA1 ion channels in cold pain perception, the present work displaying a lack of association of TRPA1 channel expression with cold sensitivity–related measures strengthen doubts about the involvement of this channel in cold pain in humans. As clinical phases of drug development are currently involving TRP inhibitors targeting TRPM8 and TRPA1, the existence of known species differences, in particular in the function of TRPA1, underlines the rising importance of new methods to directly approach the roles of TRPs in humans.