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Peripheral immune cells, neurons and glia express CB\n                    <jats:sub>2<\/jats:sub>\n                    ; however, the involvement of CB\n                    <jats:sub>2<\/jats:sub>\n                    from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB\n                    <jats:sub>2<\/jats:sub>\n                    agonist JWH133 in wild-type and knockout mice lacking CB\n                    <jats:sub>2<\/jats:sub>\n                    in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB\n                    <jats:sub>2<\/jats:sub>\n                    disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB\n                    <jats:sub>2<\/jats:sub>\n                    knockouts and was increased in mice defective in neuronal CB\n                    <jats:sub>2<\/jats:sub>\n                    knockouts suggestive of increased spontaneous pain. Interestingly, CB\n                    <jats:sub>2<\/jats:sub>\n                    -positive lymphocytes infiltrated the injured nerve and possible CB\n                    <jats:sub>2<\/jats:sub>\n                    transfer from immune cells to neurons was found. Lymphocyte CB\n                    <jats:sub>2<\/jats:sub>\n                    depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB\n                    <jats:sub>2<\/jats:sub>\n                    that protects against spontaneous and evoked neuropathic pain.\n                  <\/jats:p>","DOI":"10.7554\/elife.55582","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T08:01:11Z","timestamp":1595232071000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.55582","source":"Crossref","is-referenced-by-count":44,"title":["Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-0908","authenticated-orcid":true,"given":"David","family":"Caba\u00f1ero","sequence":"first","affiliation":[{"name":"Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain"},{"name":"Institute of Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE), Universidad Miguel Hern\u00e1ndez de Elche, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Ram\u00edrez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Drews","sequence":"additional","affiliation":[{"name":"Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Schm\u00f6le","sequence":"additional","affiliation":[{"name":"Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Otte","sequence":"additional","affiliation":[{"name":"Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Wawrzczak-Bargiela","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Huerga Encabo","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain"},{"name":"Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Kummer","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ferrer-Montiel","sequence":"additional","affiliation":[{"name":"Institute of Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE), Universidad Miguel Hern\u00e1ndez de Elche, Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard","family":"Przewlocki","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Psychiatry, University of Bonn, Bonn, 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