A TRP channel trio mediates acute noxious heat sensing

A TRP channel trio mediates acute noxious heat sensing

Nature 555, 7698 (2018). doi:10.1038/nature26137

Authors: Ine Vandewauw, Katrien De Clercq, Marie Mulier, Katharina Held, Silvia Pinto, Nele Van Ranst, Andrei Segal, Thierry Voet, Rudi Vennekens, Katharina Zimmermann, Joris Vriens & Thomas Voets
Acute pain represents a crucial alarm signal to protect us from injury. Whereas the nociceptive neurons that convey pain signals were described more than a century ago, the molecular sensors that detect noxious thermal or mechanical insults have yet to be fully identified. Here we show that acute noxious heat sensing in mice depends on a triad of transient receptor potential (TRP) ion channels: TRPM3, TRPV1, and TRPA1. We found that robust somatosensory heat responsiveness at the cellular and behavioural levels is observed only if at least one of these TRP channels is functional. However, combined genetic or pharmacological elimination of all three channels largely and selectively prevents heat responses in both isolated sensory neurons and rapidly firing C and Aδ sensory nerve fibres that innervate the skin. Strikingly, Trpv1−/−Trpm3−/−Trpa1−/− triple knockout (TKO) mice lack the acute withdrawal response to noxious heat that is necessary to avoid burn injury, while showing normal nociceptive responses to cold or mechanical stimuli and a preserved preference for moderate temperatures. These findings indicate that the initiation of the a...

Source: Nature - March 14, 2018 Category: Research Authors: Ine Vandewauw Katrien De Clercq Marie Mulier Katharina Held Silvia Pinto Nele Van Ranst Andrei Segal Thierry Voet Rudi Vennekens Katharina Zimmermann Joris Vriens Thomas Voets Tags: Letter Source Type: research