Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Coexpression of Vanilloid Receptor Subtype-1 and Acid-sensing Ion Channel Genes in the Human Trigeminal Ganglion Neurons
1 Department of Molecular Morphology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan and 2 Department of Forensic Medical Science, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
Correspondence to be sent to: Shinya Ugawa, e-mail: ugawa{at}med.nagoya-cu.ac.jp
Key words: acidosis, ASIC, colocalization, pain, proton, trigeminal ganglion, TRPV1
Previous psychophysical experiments have shown that repeated applications of high
concentrations of acids on one side of the dorsal surface of the human tongue evoke
irritation or pain (Dessirier et al.,
2000
). Under acidification, protons dissociated from the acids probably
activate excitatory cation channels expressed in local nociceptors that originate from
trigeminal ganglia, leading to the generation of such sensations. Recent molecular
investigations into sensory neurons have revealed that a transient receptor
potential/vanilloid receptor subtype-1 (TRPV1) and an acid-sensing ion channel (ASIC)
mediate the greater part of proton-induced irritation or nociception in mammals
(Julius and Basbaum, 2001;
Ugawa et al., 2003). Here we
provide evidence for involvement of both channels in acid-evoked pain in humans and show
their relative contributions to acid-evoked nociception. In our human pain model
(approved by the Ethics Committee of Nagoya City University and conducted in accordance
with the Declaration of Helsinki), direct infusion of acidic solutions (pH 
6.0) into
human skin caused localized pain, which was blocked by amiloride, an inhibitor of ASICs,
but not by capsazepine, an inhibitor of TRPV1. Although the efficacy of amiloride was
only partially attenuated under more severe acidification (pH 5.0), capsazepine produced
some blocking effect on pH 5-evoked pain. Amiloride itself neither blocked
capsaicin-evoked localized pain in human skin nor inhibited proton-induced currents in
TRPV1-expressing Xenopus oocytes (Ugawa
et al., 2003). In situ hybridization histochemistry
demonstrated that more than half of TRPV1-expressing dorsal root ganglion neurons were
ASIC1a- or ASIC3-positive in the rat, and that approximately half of TRPV1-expressing
human trigeminal neurons were ASIC-positive (S. Ugawa, T. Ueda and S. Shimada, submitted
for publication). These results suggest that ASICs are the leading acid sensors in human
nociceptors and that both TRPV1 and ASIC channels are involved in acid-evoked oral
irritation or pain.
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References |
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 Top References |
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Dessirier, J.M., O’Mahony, M., Iodi-Carstens, M. and Carstens, E. (2000) Sensory properties of citric acid: psychophysical evidence for sensitization, self-desensitization, cross-desensitization and cross-stimulus-induced recovery following capsaicin. Chem. Senses, 25, 769–780.
Julius, D. and Basbaum, A.I. (2001) Molecular mechanisms of nociception. Nature, 413, 203–210.[CrossRef][Medline]
Ugawa, S., Ueda, T. and Shimada, S. (2003) Acid-sensing ion channels and pain: therapeutic potential? Expert Rev. Neurotherap., 3, 609–619.[CrossRef]
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