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

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 se...

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Detalles Bibliográficos
Autores: Cabañero Ferri, David, Ramírez-López, Angela, Drews, Eva, Schmöle, Anne, Otte, David M., Wawrzczak-Bargiela, Agnieszka, Huerga Encabo, Hector, 1989-, Kummer, Sami, 1985-, Ferrer-Montiel, Antonio, Przewlocki, Ryszard, Zimmer, Andreas, Maldonado, Rafael, 1961-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución: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:10230/47932
Acceso en línea:http://hdl.handle.net/10230/47932
http://dx.doi.org/10.7554/eLife.55582
Access Level:acceso abierto
Palabra clave:Cannabinoid cb2 receptor
Human biology
Medicine
mouse
Neuroimmune interactions
Neuronal and lymphocyte cannabinoid receptors
Neuropathic pain
Neuroscience
Operant drug self-administration
Spontaneous pain
Descripción
Sumario: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.