TRPV1 in brain is involved in acetaminophen-induced antinociception.

<h4>Background</h4>Acetaminophen, the major active metabolite of acetanilide in man, has become one of the most popular over-the-counter analgesic and antipyretic agents, consumed by millions of people daily. However, its mechanism of action is still a matter of debate. We have previousl...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Christophe Mallet, David A Barrière, Anna Ermund, Bo A G Jönsson, Alain Eschalier, Peter M Zygmunt, Edward D Högestätt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0d3a139e7083454482747a8944cb98df
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0d3a139e7083454482747a8944cb98df
record_format	dspace
spelling	oai:doaj.org-article:0d3a139e7083454482747a8944cb98df2021-11-18T06:35:03ZTRPV1 in brain is involved in acetaminophen-induced antinociception.1932-620310.1371/journal.pone.0012748https://doaj.org/article/0d3a139e7083454482747a8944cb98df2010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20862299/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Acetaminophen, the major active metabolite of acetanilide in man, has become one of the most popular over-the-counter analgesic and antipyretic agents, consumed by millions of people daily. However, its mechanism of action is still a matter of debate. We have previously shown that acetaminophen is further metabolized to N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z -eicosatetraenamide (AM404) by fatty acid amide hydrolase (FAAH) in the rat and mouse brain and that this metabolite is a potent activator of transient receptor potential vanilloid 1 (TRPV(1)) in vitro. Pharmacological activation of TRPV(1) in the midbrain periaqueductal gray elicits antinociception in rats. It is therefore possible that activation of TRPV(1) in the brain contributes to the analgesic effect of acetaminophen.<h4>Methodology/principal findings</h4>Here we show that the antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity is absent in FAAH and TRPV(1) knockout mice in the formalin, tail immersion and von Frey tests. This dose of acetaminophen did not affect the global brain contents of prostaglandin E(2) (PGE(2)) and endocannabinoids. Intracerebroventricular injection of AM404 produced a TRPV(1)-mediated antinociceptive effect in the mouse formalin test. Pharmacological inhibition of TRPV(1) in the brain by intracerebroventricular capsazepine injection abolished the antinociceptive effect of oral acetaminophen in the same test.<h4>Conclusions</h4>This study shows that TRPV(1) in brain is involved in the antinociceptive action of acetaminophen and provides a strategy for developing central nervous system active oral analgesics based on the coexpression of FAAH and TRPV(1) in the brain.Christophe MalletDavid A BarrièreAnna ErmundBo A G JönssonAlain EschalierPeter M ZygmuntEdward D HögestättPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christophe Mallet David A Barrière Anna Ermund Bo A G Jönsson Alain Eschalier Peter M Zygmunt Edward D Högestätt TRPV1 in brain is involved in acetaminophen-induced antinociception.
description	<h4>Background</h4>Acetaminophen, the major active metabolite of acetanilide in man, has become one of the most popular over-the-counter analgesic and antipyretic agents, consumed by millions of people daily. However, its mechanism of action is still a matter of debate. We have previously shown that acetaminophen is further metabolized to N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z -eicosatetraenamide (AM404) by fatty acid amide hydrolase (FAAH) in the rat and mouse brain and that this metabolite is a potent activator of transient receptor potential vanilloid 1 (TRPV(1)) in vitro. Pharmacological activation of TRPV(1) in the midbrain periaqueductal gray elicits antinociception in rats. It is therefore possible that activation of TRPV(1) in the brain contributes to the analgesic effect of acetaminophen.<h4>Methodology/principal findings</h4>Here we show that the antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity is absent in FAAH and TRPV(1) knockout mice in the formalin, tail immersion and von Frey tests. This dose of acetaminophen did not affect the global brain contents of prostaglandin E(2) (PGE(2)) and endocannabinoids. Intracerebroventricular injection of AM404 produced a TRPV(1)-mediated antinociceptive effect in the mouse formalin test. Pharmacological inhibition of TRPV(1) in the brain by intracerebroventricular capsazepine injection abolished the antinociceptive effect of oral acetaminophen in the same test.<h4>Conclusions</h4>This study shows that TRPV(1) in brain is involved in the antinociceptive action of acetaminophen and provides a strategy for developing central nervous system active oral analgesics based on the coexpression of FAAH and TRPV(1) in the brain.
format	article
author	Christophe Mallet David A Barrière Anna Ermund Bo A G Jönsson Alain Eschalier Peter M Zygmunt Edward D Högestätt
author_facet	Christophe Mallet David A Barrière Anna Ermund Bo A G Jönsson Alain Eschalier Peter M Zygmunt Edward D Högestätt
author_sort	Christophe Mallet
title	TRPV1 in brain is involved in acetaminophen-induced antinociception.
title_short	TRPV1 in brain is involved in acetaminophen-induced antinociception.
title_full	TRPV1 in brain is involved in acetaminophen-induced antinociception.
title_fullStr	TRPV1 in brain is involved in acetaminophen-induced antinociception.
title_full_unstemmed	TRPV1 in brain is involved in acetaminophen-induced antinociception.
title_sort	trpv1 in brain is involved in acetaminophen-induced antinociception.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/0d3a139e7083454482747a8944cb98df
work_keys_str_mv	AT christophemallet trpv1inbrainisinvolvedinacetaminopheninducedantinociception AT davidabarriere trpv1inbrainisinvolvedinacetaminopheninducedantinociception AT annaermund trpv1inbrainisinvolvedinacetaminopheninducedantinociception AT boagjonsson trpv1inbrainisinvolvedinacetaminopheninducedantinociception AT alaineschalier trpv1inbrainisinvolvedinacetaminopheninducedantinociception AT petermzygmunt trpv1inbrainisinvolvedinacetaminopheninducedantinociception AT edwarddhogestatt trpv1inbrainisinvolvedinacetaminopheninducedantinociception
_version_	1718424459327569920

TRPV1 in brain is involved in acetaminophen-induced antinociception.

Ejemplares similares