Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for animal nociception

All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea and that the conserved ion channel TRPA1 is required for these responses. TRPA1-mutant Drosophila flies are also defective in noxious-heat responses. We find that either planarian or human TRPA1 can restore noxious-heat avoidance to TRPA1-mutant Drosophila , although neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H 2 O 2 and reactive oxygen species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago. Animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is poorly understood. The authors reveal a core function for TRPA1 in noxious heat transduction based on sensing H 2 O 2 and ROS and demonstrate its conservation from planarians to humans.