King's College London

The molecular mechanisms that underlie the distinct sensations of warmth and heat have remained unclear until recently. In 2016 we showed that the transient receptor potential (TRP) ion channel TRPM2 mediates the sensation of warmth in vivo in mice1, whereas in 2018 Vandewauw et al.2 found that three channels—TRPV1, TRPM3 and TRPA1—jointly mediate the sensation of painful heat. However, there was a discrepancy between the studies: we found that TRPM2 contributed to the thermal response of isolated somatosensory neurons1,3, whereas Vandewauw et al.2 proposed that TRPA1—and not TRPM2—was the only thermally activated ion channel in somatosensory neurons apart from TRPV1 and TRPM32. Here we show that both TRPM2 and TRPA1, in addition to the established thermosensory ion channels TRPV1 and TRPM3, drive responses of sensory neurons to increases of temperature.