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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.
J Neurosci 2000; 20(15):RC90JN

Abstract

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 alpha,beta-methylene ATP (alpha(beta)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 alpha(beta)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 alpha(beta)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 alpha(beta)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.

Authors+Show Affiliations

Section of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10899177

Citation

Tsuda, M, et al. "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." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 20, no. 15, 2000, pp. RC90.
Tsuda M, Koizumi S, Kita A, et al. 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. J Neurosci. 2000;20(15):RC90.
Tsuda, M., Koizumi, S., Kita, A., Shigemoto, Y., Ueno, S., & Inoue, K. (2000). 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. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 20(15), pp. RC90.
Tsuda M, et al. 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. J Neurosci. 2000 Aug 1;20(15):RC90. PubMed PMID: 10899177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Tsuda,M, AU - Koizumi,S, AU - Kita,A, AU - Shigemoto,Y, AU - Ueno,S, AU - Inoue,K, PY - 2000/7/19/pubmed PY - 2002/4/9/medline PY - 2000/7/19/entrez SP - RC90 EP - RC90 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 20 IS - 15 N2 - 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 alpha,beta-methylene ATP (alpha(beta)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 alpha(beta)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 alpha(beta)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 alpha(beta)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. SN - 0270-6474 UR - https://www.unboundmedicine.com/medline/citation/10899177/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_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=10899177 DB - PRIME DP - Unbound Medicine ER -