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The Journal of Neuroscience, 0000, 20:RC90:1-5
RAPID COMMUNICATION
Mechanical Allodynia Caused by Intraplantar Injection of P2X
Receptor Agonist in Rats: Involvement of Heteromeric P2X2/3
Receptor Signaling in Capsaicin-Insensitive Primary Afferent
Neurons
Makoto
Tsuda1,
Schuichi
Koizumi1,
Aya
Kita1,
Yukari
Shigemoto1,
Shinya
Ueno2, and
Kazuhide
Inoue1, 3
1 Section of Neuropharmacology, Division of
Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga,
Setagaya-ku, Tokyo 158-8501, Japan, 2 Department of
Pharmacology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jyonan-ku, Fukuoka 814-0180, Japan, and
3 Graduate School of Pharmaceutical Sciences, Kyushu
University, 3-1-1 Maidashi Higashi, Fukuoka 812-8582, Japan
Extracellular ATP has been known to activate sensory neurons via
the ATP-gated ion channels P2X receptors, indicating that the P2X
receptors may play a role in signal transduction of pain from the
periphery to the spinal cord in vivo.
Here, we found a novel nociceptive response induced by ATP, mechanical
allodynia (hypersensitivity to innocuous mechanical stimulus).
Injection of , -methylene ATP ( meATP), an agonist to P2X
receptor, into plantar surface in rats produced the mechanical
allodynia along with previously described nocifensive behavior and
thermal hyperalgesia. This allodynic response was blocked by
pretreatment with the P2 receptor antagonist
pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate. Interestingly, only
the mechanical allodynia evoked by  meATP selectively remained in
neonatal capsaicin-treated adult rats that had selectively lost the
capsaicin-sensitive neurons. ATP has been shown to produce two
distinguishable electrophysiological responses (inward currents with
rapid and slow desensitization) in dorsal root ganglion (DRG) neurons.
In the present electrophysiological experiment, the percentage of DRG
neurons that responded to  meATP with slow desensitizing inward
current remained constant in capsaicin-treated rats, whereas the
percentage that responded with rapid desensitizing current dramatically
decreased. Taken together with our previous finding that the
 meATP-activated slow desensitizing current in DRG neurons is
mediated by heteromeric P2X2/3 (P2X2 and
P2X3) receptors, it is hypothesized that activation
of heteromeric P2X2/3 receptors in peripheral terminals of
capsaicin-insensitive primary afferent fibers leads to the induction of
mechanical allodynia.
Key words:
, -methylene ATP; P2X receptors; mechanical
allodynia; dorsal root ganglia; primary afferent fibers; capsaicin
sensitivity
Copyright © 0000 Society for Neuroscience 0270-6474/00/$05.00/0
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