Heat sensing involves a TRiPlet of ion channels.

Detecting and avoiding noxious heat is crucial to prevent burn injury. While the nociceptor neurons involved in conveying heat-induced pain were identified more than a century ago, the molecular sensors responsible for detecting noxious heat had remained elusive. In a recent study, important progress was made in our understanding of the molecular basis of acute noxious heat sensing, with the identification of a set of three transient receptor potential (TRP) ion channels, TRPV1, TRPA1, and TRPM3, which have crucial but largely redundant roles in acute heat sensing. Most strikingly, combined elimination of all three TRP channels causes a complete loss of the acute avoidance reaction to noxious heat, without affecting pain responses to painful mechanical or cold stimuli. Here, we provide a brief account of the current model of acute, noxious heat sensing and discuss possible implications for analgesic drug development.