Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation.
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.
Bang
Sangsu
S
Korea University Graduate School of Medicine, Seoul 136-705, Korea.
Kim
Kyung Yoon
KY
Yoo
Sungjae
S
Kim
Yoon Gyoon
YG
Hwang
Sun Wook
SW
D000079:Acetaldehyde / Q000378:metabolism / Q000494:pharmacology*; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002164:Camphor / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D012430:Ruthenium Red / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D012430:Ruthenium Red; D000431:Ethanol; D002164:Camphor; D005682:Gadolinium; D000079:Acetaldehyde; D015232:Dinoprostone