Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation

Eur J Neurosci. 2007 Nov;26(9):2516-23. doi: 10.1111/j.1460-9568.2007.05882.x. Epub 2007 Oct 23.


Six transient receptor potential (TRP) ion channels expressed in the sensory afferents play an important role as body thermosensors and also as peripheral pain detectors. It is known that a number of natural compounds specifically activate those sensory neuronal TRP channels, and a well-known example is cinnamaldehyde for TRPA1. Here we show that human and mouse TRPA1 are activated by acetaldehyde, an intermediate substance of ethanol metabolism, in the HEK293T cell heterologous expression system and in cultured mouse trigeminal neurons. Acetaldehyde failed to activate other temperature-sensitive TRP channels expressed in sensory neurons. TRPA1 antagonists camphor and gadolinium, and a general TRP blocker ruthenium red inhibited TRPA1 activation by acetaldehyde. Camphor, gadolinium and ruthenium red also suppressed the acute nociceptive behaviors induced by the intradermal administration of acetaldehyde into the mouse footpads. Intradermal co-application of prostaglandin E2 and acetaldehyde greatly potentiated the acetaldehyde-induced nociceptive responses, and this effect was reversed by treatment with the TRPA1 antagonist camphor. These results suggest that acetaldehyde causes nociception via TRPA1 activation. Our data may also help elucidate the mechanisms underlying acetaldehyde-related pathological symptoms such as hangover pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / metabolism
  • Acetaldehyde / pharmacology*
  • Alcohol-Induced Disorders, Nervous System / metabolism
  • Alcohol-Induced Disorders, Nervous System / physiopathology
  • Animals
  • Camphor / pharmacology
  • Cell Line
  • Cells, Cultured
  • Dinoprostone / pharmacology
  • Ethanol / metabolism
  • Ethanol / pharmacology
  • Gadolinium / pharmacology
  • Humans
  • Mice
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism
  • Nociceptors / drug effects*
  • Nociceptors / metabolism*
  • Pain / chemically induced*
  • Pain / metabolism*
  • Pain / physiopathology
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Ruthenium Red / pharmacology
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / drug effects
  • Transient Receptor Potential Channels / physiology*
  • Trigeminal Ganglion / cytology
  • Trigeminal Ganglion / drug effects
  • Trigeminal Ganglion / metabolism


  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • Ruthenium Red
  • Ethanol
  • Camphor
  • Gadolinium
  • Acetaldehyde
  • Dinoprostone