Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin

Michael Bandell, Gina M. Story, Sun Wook Hwang, Veena Viswanath, Samer R. Eid, Matt J. Petrus, Taryn J. Earley, Ardem Patapoutian

Research output: Contribution to journalArticlepeer-review

1525 Citations (Scopus)


Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.

Original languageEnglish
Pages (from-to)849-857
Number of pages9
Issue number6
Publication statusPublished - 2004 Mar 25
Externally publishedYes

Bibliographical note

Funding Information:
We thank Van Lee and Amber Murray for technical assistance; and Nancy Hong, Tim Jegla, Andrea Peier, and Lisa Stowers for valuable input. Sponsored in part by grants from NINDS (NS42822 and NS046303). S.R.E. was partially supported by a Swiss National Science Foundation fellowship. A.P. is a Damon Runyon Scholar.

ASJC Scopus subject areas

  • General Neuroscience


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