Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice

Sigma-1 receptor (σ1R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice a...

ver descrição completa

Detalhes bibliográficos
Autores: Castany, Sílvia, Gris, Georgia, Vela, José Miguel, Verdú Navarro, Enrique, Boadas i Vaello, Pere
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/18494
Acesso em linha:http://hdl.handle.net/10256/18494
Access Level:acceso abierto
Palavra-chave:Dolor neuropàtic
Neuropathic pain
Medul·la espinal -- Ferides i lesions
Spinal cord -- Wounds and injuries
id ES_c6da4d5bd2ce30bd75e00c7fe2749c5c
oai_identifier_str oai:recercat.cat:10256/18494
network_acronym_str ES
network_name_str España
repository_id_str
spelling Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in miceCastany, SílviaGris, GeorgiaVela, José MiguelVerdú Navarro, EnriqueBoadas i Vaello, PereDolor neuropàticNeuropathic painMedul·la espinal -- Ferides i lesionsSpinal cord -- Wounds and injuriesSigma-1 receptor (σ1R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) – a model of central neuropathic pain. The modulatory effect of σ1R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed. Compared with WT mice, both mechanical and thermal hypersensitivity were attenuated in σ1R KO mice following SCI. Accordingly, treatment of WT mice with the σ1R antagonist MR309 (previously developed as E-52862; S1RA) after SCI exerted antinociceptive effects (i.e. reduced mechanical allodynia and thermal hyperalgesia). Attenuated nociceptive responses in σ1R KO were accompanied by reduced expression of TNF- α and IL-1β as well as decreased activation/phosphorylation of NR2B-NMDA receptors and ERK1/2. These findings suggest that σ1R may modulate central neuropathic pain and point to regulation of sensitization-related phenomena as a possible mechanismNature Research2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/18494http://hdl.handle.net/10256/18494Scientific reports, 2018, vol. 8, art. núm. 3873Articles publicats (D-CM)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-22217-9info:eu-repo/semantics/altIdentifier/issn/2045-2322Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/184942026-05-29T05:05:01Z
dc.title.none.fl_str_mv Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
title Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
spellingShingle Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
Castany, Sílvia
Dolor neuropàtic
Neuropathic pain
Medul·la espinal -- Ferides i lesions
Spinal cord -- Wounds and injuries
title_short Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
title_full Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
title_fullStr Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
title_full_unstemmed Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
title_sort Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice
dc.creator.none.fl_str_mv Castany, Sílvia
Gris, Georgia
Vela, José Miguel
Verdú Navarro, Enrique
Boadas i Vaello, Pere
author Castany, Sílvia
author_facet Castany, Sílvia
Gris, Georgia
Vela, José Miguel
Verdú Navarro, Enrique
Boadas i Vaello, Pere
author_role author
author2 Gris, Georgia
Vela, José Miguel
Verdú Navarro, Enrique
Boadas i Vaello, Pere
author2_role author
author
author
author
dc.subject.none.fl_str_mv Dolor neuropàtic
Neuropathic pain
Medul·la espinal -- Ferides i lesions
Spinal cord -- Wounds and injuries
topic Dolor neuropàtic
Neuropathic pain
Medul·la espinal -- Ferides i lesions
Spinal cord -- Wounds and injuries
description Sigma-1 receptor (σ1R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) – a model of central neuropathic pain. The modulatory effect of σ1R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed. Compared with WT mice, both mechanical and thermal hypersensitivity were attenuated in σ1R KO mice following SCI. Accordingly, treatment of WT mice with the σ1R antagonist MR309 (previously developed as E-52862; S1RA) after SCI exerted antinociceptive effects (i.e. reduced mechanical allodynia and thermal hyperalgesia). Attenuated nociceptive responses in σ1R KO were accompanied by reduced expression of TNF- α and IL-1β as well as decreased activation/phosphorylation of NR2B-NMDA receptors and ERK1/2. These findings suggest that σ1R may modulate central neuropathic pain and point to regulation of sensitization-related phenomena as a possible mechanism
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/18494
http://hdl.handle.net/10256/18494
url http://hdl.handle.net/10256/18494
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-22217-9
info:eu-repo/semantics/altIdentifier/issn/2045-2322
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv Scientific reports, 2018, vol. 8, art. núm. 3873
Articles publicats (D-CM)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419107676323840
score 15,811543

Registos relacionados