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

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Racz, Ildikoca
  • dc.contributor.author Nadal i Roura, Xavier, 1980-ca
  • dc.contributor.author Alferink, Judithca
  • dc.contributor.author Baños i Díez, Josep Eladica
  • dc.contributor.author Rehnelt, Jenniferca
  • dc.contributor.author Martín Sánchez, Miquel, 1971-ca
  • dc.contributor.author Pintado, Belénca
  • dc.contributor.author Gutierrez-Adan, Alfonsoca
  • dc.contributor.author Sanguino, Elenaca
  • dc.contributor.author Manzanares, Jorgeca
  • dc.contributor.author Zimmer, Andreasca
  • dc.contributor.author Maldonado, Rafael, 1961-ca
  • dc.date.accessioned 2012-07-05T06:53:41Z
  • dc.date.available 2012-07-05T06:53:41Z
  • dc.date.issued 2008ca
  • dc.description.abstract 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.
  • dc.description.sponsorship 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.).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Racz I, Nadal X, Alferink J, Baños JE, Rehnelt J, Martín M et al. Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain. J. Neurosci. 2008;28(46):12125-35. DOI: 10.1523/​JNEUROSCI.3400-08.2008ca
  • dc.identifier.doi http://dx.doi.org/10.1523/JNEUROSCI.3400-08.2008
  • dc.identifier.issn 0270-6474ca
  • dc.identifier.uri http://hdl.handle.net/10230/16658
  • dc.language.iso engca
  • dc.publisher Society for Neuroscienceca
  • dc.relation.ispartof Journal of Neuroscience. 2008;28(46):12125-35
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/BFU2004-00920
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
  • dc.rights © 2008, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/28/46/12125ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.other Cannabinoides -- Efectes fisiològics
  • dc.subject.other Cannabinoides -- Receptors
  • dc.subject.other Dolor -- Tractament
  • dc.subject.other CB2 cannabinoid receptor
  • dc.subject.other Microglia
  • dc.subject.other Astrocytes
  • dc.subject.other Neuropathic pain
  • dc.subject.other Bone marrow chimera
  • dc.subject.other Neuroinflammation
  • dc.title Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic painca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersion