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...
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Format: | Article |
Language: | English |
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SAGE Publishing
2006-06-01
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Series: | Molecular Pain |
Online Access: | http://www.molecularpain.com/content/2/1/19 |
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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> |
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format | Article |
id | doaj.art-ee97098688044a75b3047adac29533f3 |
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issn | 1744-8069 |
language | English |
last_indexed | 2024-12-11T12:23:55Z |
publishDate | 2006-06-01 |
publisher | SAGE Publishing |
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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 |
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