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Media type:
E-Article
Title:
Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain
Contributor:
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
imprint:
eLife Sciences Publications, Ltd, 2020
Published in:eLife
Language:
English
DOI:
10.7554/elife.55582
ISSN:
2050-084X
Origination:
Footnote:
Description:
<jats:p>Cannabinoid CB<jats:sub>2</jats:sub> receptor (CB<jats:sub>2</jats:sub>) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB<jats:sub>2</jats:sub>; however, the involvement of CB<jats:sub>2</jats:sub> from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB<jats:sub>2</jats:sub> agonist JWH133 in wild-type and knockout mice lacking CB<jats:sub>2</jats:sub> in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB<jats:sub>2</jats:sub> disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB<jats:sub>2</jats:sub> knockouts and was increased in mice defective in neuronal CB<jats:sub>2</jats:sub> knockouts suggestive of increased spontaneous pain. Interestingly, CB<jats:sub>2</jats:sub>-positive lymphocytes infiltrated the injured nerve and possible CB<jats:sub>2</jats:sub>transfer from immune cells to neurons was found. Lymphocyte CB<jats:sub>2</jats:sub>depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB<jats:sub>2</jats:sub>that protects against spontaneous and evoked neuropathic pain.</jats:p>