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

Abstract

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 flies (Drosophila) are also defective in noxious heat responses. Unexpectedly, we find that either planarian or human TRPA1 can restore noxious heat avoidance to TRPA1 mutant Drosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/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.

Pharmacological or genetic targeting of Transient Receptor Potential (TRP) channels can disrupt the planarian escape response

“…These fragments were cloned into the pPR244-TRP vector using ligase independent cloning (45). The Smed-TRPA1-pGEMt plasmid was a gift from Dr. Marco Gallio (10).…”

“…Recently, it has been shown using RNA interference (RNAi) that the Transient Receptor Potential (TRP) channel, TRP ankyrin 1 (TRPA1), is required for avoidance behaviors in Schmidtea mediterranea in response to noxious heat and the pungent ingredient in mustard oil, allyl isothiocyanate (AITC) (10). The authors also showed that the noxious heat response was mediated by H 2 O 2 and/or reactive oxygen species which directly activate TRPA1, causing the planarian to avoid hot regions.…”

“…The authors also showed that the noxious heat response was mediated by H 2 O 2 and/or reactive oxygen species which directly activate TRPA1, causing the planarian to avoid hot regions. Moreover, in response to physical injury (tail snips), Smed-TRPA1 -knockdown worms scrunched with a significantly reduced amplitude (10). Based on these results, the authors hypothesized that TRPA1 signaling, induced through H 2 O 2 upregulation at the site of wounding, may regulate amputation-induced-scrunching in S. mediterranea .…”

“…To test this hypothesis, we first assayed a variety of chemicals for their ability to induce scrunching in two freshwater planarian species, S. mediterranea and D. japonica. We focused on chemical compounds that have been shown to activate TRPA1 and/or TRPV, such as AITC, an agonist of planarian (10) and mammalian (31,32) TRPA1, and capsaicin, a specific agonist of mammalian TRPV1 (33,34).…”

Evolution of olfactory receptors tuned to mustard oils in herbivorous Drosophilidae

“…In animals, the only known and broadly conserved electrophile detecting sensors are the Transient Receptor Potential (TRP) nociceptive channel family (5)(6)(7), and the most studied among them is the Transient Receptor Potential Ankyrin-1 (TrpA1) (8)(9)(10). Reactive Brassicales plants typically produce ITCs upon tissue damage, which are highly toxic to non-adapted insects but not to mustard specialists, including S. flava (24).…”