Protective role of neuronal and lymphoid cannabinoid CB 2 receptors in neuropathic pain

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• dc.contributor.author Cabañero Ferri, David
• dc.contributor.author Ramírez-López, Angela
• dc.contributor.author Drews, Eva
• dc.contributor.author Schmöle, Anne
• dc.contributor.author Otte, David M.
• dc.contributor.author Wawrzczak-Bargiela, Agnieszka
• dc.contributor.author Huerga Encabo, Hector, 1989-
• dc.contributor.author Kummer, Sami, 1985-
• dc.contributor.author Ferrer-Montiel, Antonio
• dc.contributor.author Przewlocki, Ryszard
• dc.contributor.author Zimmer, Andreas
• dc.contributor.author Maldonado, Rafael, 1961-
• dc.date.accessioned 2021-06-18T06:52:29Z
• dc.date.available 2021-06-18T06:52:29Z
• dc.date.issued 2020
• dc.description.abstract Cannabinoid CB2 receptor (CB2) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB2; however, the involvement of CB2 from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB2 agonist JWH133 in wild-type and knockout mice lacking CB2 in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB2 disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB2 knockouts and was increased in mice defective in neuronal CB2 knockouts suggestive of increased spontaneous pain. Interestingly, CB2-positive lymphocytes infiltrated the injured nerve and possible CB2transfer from immune cells to neurons was found. Lymphocyte CB2depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB2that protects against spontaneous and evoked neuropathic pain.
• dc.description.sponsorship This paper was supported by the following grants: European Commission NeuroPain, FP7-602891-2 to Rafael Maldonado. Instituto de Salud Carlos III RTA, RD16/0017/0020/FEDER to Rafael Maldonado. Ministerio de Ciencia, Innovación y Universidades SAF2017-84060-R FEDER to Rafael Maldonado. Generalitat de Catalunya SGR2017-669, ICREA Academia Award 2015 to Rafael Maldonado. Generalitat de Catalunya 2018 FI_B 00207 to Angela Ramírez-López. Polish Ministry of Science and Education 3070/7.PR/2014/2 to Ryszard Przewlocki. Spanish Ministry of Science, Innovation and Universities 2018-097189-B-C21 to Antonio Ferrer-Montiel. Universidad Miguel Hernandez UMH-PAR2019 to Antonio Ferrer-Montiel.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cabañero D, Ramírez-López A, Drews E, Schmöle A, Otte DM, Wawrzczak-Bargiela A, Huerga Encabo H, Kummer S, Ferrer-Montiel A, Przewlocki R, Zimmer A, Maldonado R. Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain. Elife. 2020 Jul 20; 9: e55582. DOI: 10.7554/eLife.55582
• dc.identifier.doi http://dx.doi.org/10.7554/eLife.55582
• dc.identifier.issn 2050-084X
• dc.identifier.uri http://hdl.handle.net/10230/47932
• dc.language.iso eng
• dc.publisher eLife
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-84060-R
• dc.rights Copyright © 2020, Cabañero et al. This article is distributed under the terms of the Creative Commons Attribution License, http://creativecommons.org/licenses/by/4.0/ which permits unrestricted use and redistribution provided that the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Cannabinoid cb2 receptor
• dc.subject.keyword Human biology
• dc.subject.keyword Medicine
• dc.subject.keyword mouse
• dc.subject.keyword Neuroimmune interactions
• dc.subject.keyword Neuronal and lymphocyte cannabinoid receptors
• dc.subject.keyword Neuropathic pain
• dc.subject.keyword Neuroscience
• dc.subject.keyword Operant drug self-administration
• dc.subject.keyword Spontaneous pain
• dc.title Protective role of neuronal and lymphoid cannabinoid CB 2 receptors in neuropathic pain
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion