Inhibitory role of supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>subtypes on nociception in rats

<p>Abstract</p> <p>Extracellular ATP is known to mediate synaptic transmission as a neurotransmitter or a neuromodulator via ionotropic P2X and metabotropic P2Y receptors. Several lines of evidence have suggested that ATP facilitates pain transmission at peripheral and spinal sites...

Full description

Bibliographic Details
Main Authors: Satoh Masamichi, Minami Masabumi, Nakagawa Takayuki, Fukui Masato, Kaneko Shuji
Format: Article
Language:English
Published: SAGE Publishing 2006-06-01
Series:Molecular Pain
Online Access:http://www.molecularpain.com/content/2/1/19
_version_ 1828496096344670208
author Satoh Masamichi
Minami Masabumi
Nakagawa Takayuki
Fukui Masato
Kaneko Shuji
author_facet Satoh Masamichi
Minami Masabumi
Nakagawa Takayuki
Fukui Masato
Kaneko Shuji
author_sort Satoh Masamichi
collection DOAJ
description <p>Abstract</p> <p>Extracellular ATP is known to mediate synaptic transmission as a neurotransmitter or a neuromodulator via ionotropic P2X and metabotropic P2Y receptors. Several lines of evidence have suggested that ATP facilitates pain transmission at peripheral and spinal sites via the P2X receptors, in which the P2X<sub>3 </sub>subtype is considered as an important candidate for the effect. Conversely, we previously found that the activation of supraspinal P2X receptors evoked antinociception. However, the subtypes responsible for the antinociception via supraspinal P2X receptors remain unclear. In the present study, we showed that intracerebroventricular (i.c.v.) pretreatment with A-317491 (1 nmol), the novel non-nucleotide antagonist selective for P2X<sub>3 </sub>and P2X<sub>2/3 </sub>receptors, attenuated the antinociceptive effect produced by i.c.v. administered α,β-methylene-ATP (10 nmol), the P2X receptor agonist, in rats. Similarly, the abolishment of the P2X<sub>3 </sub>receptor mRNA in the brainstem by repeated i.c.v. pretreatments with antisense oligodeoxynucleotide for P2X<sub>3 </sub>gene once a day for 5 consecutive days diminished the antinociceptive effect of α,β-methylene-ATP. Furthermore, i.c.v. administration of A-317491 (1 and 10 nmol) significantly enhanced the inflammatory nociceptive behaviors induced by the intraplantar injection of formalin and intraperitoneal injection of acetic acid. Taken together, these results suggest that supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>receptors play an inhibitory role in pain transmission.</p>
first_indexed 2024-12-11T12:23:55Z
format Article
id doaj.art-ee97098688044a75b3047adac29533f3
institution Directory Open Access Journal
issn 1744-8069
language English
last_indexed 2024-12-11T12:23:55Z
publishDate 2006-06-01
publisher SAGE Publishing
record_format Article
series Molecular Pain
spelling doaj.art-ee97098688044a75b3047adac29533f32022-12-22T01:07:28ZengSAGE PublishingMolecular Pain1744-80692006-06-01211910.1186/1744-8069-2-19Inhibitory role of supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>subtypes on nociception in ratsSatoh MasamichiMinami MasabumiNakagawa TakayukiFukui MasatoKaneko Shuji<p>Abstract</p> <p>Extracellular ATP is known to mediate synaptic transmission as a neurotransmitter or a neuromodulator via ionotropic P2X and metabotropic P2Y receptors. Several lines of evidence have suggested that ATP facilitates pain transmission at peripheral and spinal sites via the P2X receptors, in which the P2X<sub>3 </sub>subtype is considered as an important candidate for the effect. Conversely, we previously found that the activation of supraspinal P2X receptors evoked antinociception. However, the subtypes responsible for the antinociception via supraspinal P2X receptors remain unclear. In the present study, we showed that intracerebroventricular (i.c.v.) pretreatment with A-317491 (1 nmol), the novel non-nucleotide antagonist selective for P2X<sub>3 </sub>and P2X<sub>2/3 </sub>receptors, attenuated the antinociceptive effect produced by i.c.v. administered α,β-methylene-ATP (10 nmol), the P2X receptor agonist, in rats. Similarly, the abolishment of the P2X<sub>3 </sub>receptor mRNA in the brainstem by repeated i.c.v. pretreatments with antisense oligodeoxynucleotide for P2X<sub>3 </sub>gene once a day for 5 consecutive days diminished the antinociceptive effect of α,β-methylene-ATP. Furthermore, i.c.v. administration of A-317491 (1 and 10 nmol) significantly enhanced the inflammatory nociceptive behaviors induced by the intraplantar injection of formalin and intraperitoneal injection of acetic acid. Taken together, these results suggest that supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>receptors play an inhibitory role in pain transmission.</p>http://www.molecularpain.com/content/2/1/19
spellingShingle Satoh Masamichi
Minami Masabumi
Nakagawa Takayuki
Fukui Masato
Kaneko Shuji
Inhibitory role of supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>subtypes on nociception in rats
Molecular Pain
title Inhibitory role of supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>subtypes on nociception in rats
title_full Inhibitory role of supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>subtypes on nociception in rats
title_fullStr Inhibitory role of supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>subtypes on nociception in rats
title_full_unstemmed Inhibitory role of supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>subtypes on nociception in rats
title_short Inhibitory role of supraspinal P2X<sub>3</sub>/P2X<sub>2/3 </sub>subtypes on nociception in rats
title_sort inhibitory role of supraspinal p2x sub 3 sub p2x sub 2 3 sub subtypes on nociception in rats
url http://www.molecularpain.com/content/2/1/19
work_keys_str_mv AT satohmasamichi inhibitoryroleofsupraspinalp2xsub3subp2xsub23subsubtypesonnociceptioninrats
AT minamimasabumi inhibitoryroleofsupraspinalp2xsub3subp2xsub23subsubtypesonnociceptioninrats
AT nakagawatakayuki inhibitoryroleofsupraspinalp2xsub3subp2xsub23subsubtypesonnociceptioninrats
AT fukuimasato inhibitoryroleofsupraspinalp2xsub3subp2xsub23subsubtypesonnociceptioninrats
AT kanekoshuji inhibitoryroleofsupraspinalp2xsub3subp2xsub23subsubtypesonnociceptioninrats