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

• Published in: eLife 2020-07, Vol.9
• Main Authors: Cabañero, David, Ramírez-López, Angela, Drews, Eva, Schmöle, Anne, Otte, David M, Wawrzczak-Bargiela, Agnieszka, Huerga Encabo, Hector, Kummer, Sami, Ferrer-Montiel, Antonio, Przewlocki, Ryszard, Zimmer, Andreas, Maldonado, Rafael
• Format: Article
• Language: English
• Subjects: Lymphocytes; Neurons
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.55582

Cannabinoid CB.sub.2 receptor (CB.sub.2) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB.sub.2; however, the involvement of CB.sub.2 from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB.sub.2 agonist JWH133 in wild-type and knockout mice lacking CB.sub.2 in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB.sub.2 disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB.sub.2 knockouts and was increased in mice defective in neuronal CB.sub.2 knockouts suggestive of increased spontaneous pain. Interestingly, CB.sub.2-positive lymphocytes infiltrated the injured nerve and possible CB.sub.2transfer from immune cells to neurons was found. Lymphocyte CB.sub.2depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB.sub.2that protects against spontaneous and evoked neuropathic pain.