Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain

Neuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB2 cannabinoid receptors in the regulation of the central immune responses leading to the de...

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Autores: Racz, Ildiko, Nadal i Roura, Xavier, 1980-, Alferink, Judith, Baños i Díez, Josep Eladi, Rehnelt, Jennifer, Martín Sánchez, Miquel, 1971-, Pintado, Belén, Gutierrez-Adan, Alfonso, Sanguino, Elena, Manzanares, Jorge, Zimmer, Andreas, Maldonado, Rafael, 1961-
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2008
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/16658
Acesso em linha:http://hdl.handle.net/10230/16658
http://dx.doi.org/10.1523/JNEUROSCI.3400-08.2008
Access Level:Acceso aberto
Palavra-chave:Cannabinoides -- Efectes fisiològics
Cannabinoides -- Receptors
Dolor -- Tractament
CB2 cannabinoid receptor
Microglia
Astrocytes
Neuropathic pain
Bone marrow chimera
Neuroinflammation
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repository_id_str
spelling Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic painRacz, IldikoNadal i Roura, Xavier, 1980-Alferink, JudithBaños i Díez, Josep EladiRehnelt, JenniferMartín Sánchez, Miquel, 1971-Pintado, BelénGutierrez-Adan, AlfonsoSanguino, ElenaManzanares, JorgeZimmer, AndreasMaldonado, Rafael, 1961-Cannabinoides -- Efectes fisiològicsCannabinoides -- ReceptorsDolor -- TractamentCB2 cannabinoid receptorMicrogliaAstrocytesNeuropathic painBone marrow chimeraNeuroinflammationNeuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB2 cannabinoid receptors in the regulation of the central immune responses leading to the development of neuropathic pain. CB2 knock-out mice and wild-type littermates were exposed to sciatic nerve injury, and both genotypes developed a similar hyperalgesia and allodynia in the ipsilateral paw. Most strikingly, knock-outs also developed a contralateral mirror image pain, associated with an enhanced microglial and astrocytic expression in the contralateral spinal horn. In agreement, hyperalgesia, allodynia, and microglial and astrocytic activation induced by sciatic nerve injury were attenuated in transgenic mice overexpressing CB2 receptors. These results demonstrate the crucial role of CB2 cannabinoid receptor in modulating glial activation in response to nerve injury. The enhanced manifestations of neuropathic pain were replicated in irradiated wild-type mice reconstituted with bone marrow cells from CB2 knock-outs, thus demonstrating the implication of the CB2 receptor expressed in hematopoietic cells in the development of neuropathic pain at the spinal cord.This work was supported by grants from the National Institute on Drug Abuse (1R01-DA016768-0111) (R.M.,A.Z.), European Commission [Framework VI, GENADDICT OJ 2004/C164, 005166 (R.M., A.Z.); PHECOM, LSHM-CT-2007-037669 (R.M.)], Ministerio de Educación y Ciencia (BFU2004-00920/BFI; SAF2007-64062) (R.M.), Generalitat de Catalunya (R.M.), Deutsche Forschungsgemeinschaft (SFB645; FOR926) (A.Z.), and Bundesministerium für Bildung und Forschung (NGFN2) (A.Z.).Society for Neuroscience201220122008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/16658http://dx.doi.org/10.1523/JNEUROSCI.3400-08.2008reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésJournal of Neuroscience. 2008;28(46):12125-35info:eu-repo/grantAgreement/ES/2PN/BFU2004-00920info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062© 2008, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/28/46/12125info:eu-repo/semantics/openAccessoai:recercat.cat:10230/166582026-05-29T05:05:01Z
dc.title.none.fl_str_mv Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain
title Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain
spellingShingle Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain
Racz, Ildiko
Cannabinoides -- Efectes fisiològics
Cannabinoides -- Receptors
Dolor -- Tractament
CB2 cannabinoid receptor
Microglia
Astrocytes
Neuropathic pain
Bone marrow chimera
Neuroinflammation
title_short Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain
title_full Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain
title_fullStr Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain
title_full_unstemmed Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain
title_sort Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain
dc.creator.none.fl_str_mv Racz, Ildiko
Nadal i Roura, Xavier, 1980-
Alferink, Judith
Baños i Díez, Josep Eladi
Rehnelt, Jennifer
Martín Sánchez, Miquel, 1971-
Pintado, Belén
Gutierrez-Adan, Alfonso
Sanguino, Elena
Manzanares, Jorge
Zimmer, Andreas
Maldonado, Rafael, 1961-
author Racz, Ildiko
author_facet Racz, Ildiko
Nadal i Roura, Xavier, 1980-
Alferink, Judith
Baños i Díez, Josep Eladi
Rehnelt, Jennifer
Martín Sánchez, Miquel, 1971-
Pintado, Belén
Gutierrez-Adan, Alfonso
Sanguino, Elena
Manzanares, Jorge
Zimmer, Andreas
Maldonado, Rafael, 1961-
author_role author
author2 Nadal i Roura, Xavier, 1980-
Alferink, Judith
Baños i Díez, Josep Eladi
Rehnelt, Jennifer
Martín Sánchez, Miquel, 1971-
Pintado, Belén
Gutierrez-Adan, Alfonso
Sanguino, Elena
Manzanares, Jorge
Zimmer, Andreas
Maldonado, Rafael, 1961-
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cannabinoides -- Efectes fisiològics
Cannabinoides -- Receptors
Dolor -- Tractament
CB2 cannabinoid receptor
Microglia
Astrocytes
Neuropathic pain
Bone marrow chimera
Neuroinflammation
topic Cannabinoides -- Efectes fisiològics
Cannabinoides -- Receptors
Dolor -- Tractament
CB2 cannabinoid receptor
Microglia
Astrocytes
Neuropathic pain
Bone marrow chimera
Neuroinflammation
description Neuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB2 cannabinoid receptors in the regulation of the central immune responses leading to the development of neuropathic pain. CB2 knock-out mice and wild-type littermates were exposed to sciatic nerve injury, and both genotypes developed a similar hyperalgesia and allodynia in the ipsilateral paw. Most strikingly, knock-outs also developed a contralateral mirror image pain, associated with an enhanced microglial and astrocytic expression in the contralateral spinal horn. In agreement, hyperalgesia, allodynia, and microglial and astrocytic activation induced by sciatic nerve injury were attenuated in transgenic mice overexpressing CB2 receptors. These results demonstrate the crucial role of CB2 cannabinoid receptor in modulating glial activation in response to nerve injury. The enhanced manifestations of neuropathic pain were replicated in irradiated wild-type mice reconstituted with bone marrow cells from CB2 knock-outs, thus demonstrating the implication of the CB2 receptor expressed in hematopoietic cells in the development of neuropathic pain at the spinal cord.
publishDate 2008
dc.date.none.fl_str_mv 2008
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/16658
http://dx.doi.org/10.1523/JNEUROSCI.3400-08.2008
url http://hdl.handle.net/10230/16658
http://dx.doi.org/10.1523/JNEUROSCI.3400-08.2008
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Neuroscience. 2008;28(46):12125-35
info:eu-repo/grantAgreement/ES/2PN/BFU2004-00920
info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv 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
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score 15,812429

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