The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity

Abstract Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there is no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patien...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stephan W. Hohmann, Carlo Angioni, Sorin Tunaru, Seungkyu Lee, Clifford J. Woolf, Stefan Offermanns, Gerd Geisslinger, Klaus Scholich, Marco Sisignano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e74672e0a2c4692add969dc360ea3e5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1e74672e0a2c4692add969dc360ea3e5
record_format	dspace
spelling	oai:doaj.org-article:1e74672e0a2c4692add969dc360ea3e52021-12-02T16:07:48ZThe G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity10.1038/s41598-017-00591-02045-2322https://doaj.org/article/1e74672e0a2c4692add969dc360ea3e52017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00591-0https://doaj.org/toc/2045-2322Abstract Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there is no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patients. Here, we report the involvement of the G-protein coupled receptor G2A (GPR132) in oxaliplatin-induced neuropathic pain in mice. We found that mice deficient in the G2A-receptor show decreased mechanical hypersensitivity after oxaliplatin treatment. Lipid ligands of G2A were found in increased concentrations in the sciatic nerve and dorsal root ganglia of oxaliplatin treated mice. Calcium imaging and patch-clamp experiments show that G2A activation sensitizes the ligand-gated ion channel TRPV1 in sensory neurons via activation of PKC. Based on these findings, we conclude that targeting G2A may be a promising approach to reduce oxaliplatin-induced TRPV1-sensitization and the hyperexcitability of sensory neurons and thereby to reduce pain in patients treated with this chemotherapeutic agent.Stephan W. HohmannCarlo AngioniSorin TunaruSeungkyu LeeClifford J. WoolfStefan OffermannsGerd GeisslingerKlaus ScholichMarco SisignanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephan W. Hohmann Carlo Angioni Sorin Tunaru Seungkyu Lee Clifford J. Woolf Stefan Offermanns Gerd Geisslinger Klaus Scholich Marco Sisignano The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity
description	Abstract Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there is no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patients. Here, we report the involvement of the G-protein coupled receptor G2A (GPR132) in oxaliplatin-induced neuropathic pain in mice. We found that mice deficient in the G2A-receptor show decreased mechanical hypersensitivity after oxaliplatin treatment. Lipid ligands of G2A were found in increased concentrations in the sciatic nerve and dorsal root ganglia of oxaliplatin treated mice. Calcium imaging and patch-clamp experiments show that G2A activation sensitizes the ligand-gated ion channel TRPV1 in sensory neurons via activation of PKC. Based on these findings, we conclude that targeting G2A may be a promising approach to reduce oxaliplatin-induced TRPV1-sensitization and the hyperexcitability of sensory neurons and thereby to reduce pain in patients treated with this chemotherapeutic agent.
format	article
author	Stephan W. Hohmann Carlo Angioni Sorin Tunaru Seungkyu Lee Clifford J. Woolf Stefan Offermanns Gerd Geisslinger Klaus Scholich Marco Sisignano
author_facet	Stephan W. Hohmann Carlo Angioni Sorin Tunaru Seungkyu Lee Clifford J. Woolf Stefan Offermanns Gerd Geisslinger Klaus Scholich Marco Sisignano
author_sort	Stephan W. Hohmann
title	The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity
title_short	The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity
title_full	The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity
title_fullStr	The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity
title_full_unstemmed	The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity
title_sort	g2a receptor (gpr132) contributes to oxaliplatin-induced mechanical pain hypersensitivity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1e74672e0a2c4692add969dc360ea3e5
work_keys_str_mv	AT stephanwhohmann theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT carloangioni theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT sorintunaru theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT seungkyulee theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT cliffordjwoolf theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT stefanoffermanns theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT gerdgeisslinger theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT klausscholich theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT marcosisignano theg2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT stephanwhohmann g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT carloangioni g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT sorintunaru g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT seungkyulee g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT cliffordjwoolf g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT stefanoffermanns g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT gerdgeisslinger g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT klausscholich g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity AT marcosisignano g2areceptorgpr132contributestooxaliplatininducedmechanicalpainhypersensitivity
_version_	1718384702922948608

The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity

Ejemplares similares