Protective role of neuronal and lymphoid cannabinoid CB<sub>2</sub> receptors in neuropathic pain.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32687056.
- Also identified by DOI 10.7554/eLife.55582 and PMC identifier 7384863.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Cannabinoid CB<sub>2</sub> receptor (CB<sub>2</sub>) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB<sub>2</sub>; however, the involvement of CB<sub>2</sub> from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB<sub>2</sub> agonist JWH133 in wild-type and knockout mice lacking CB<sub>2</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<sub>2</sub> disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB<sub>2</sub> knockouts and was increased in mice defective in neuronal CB<sub>2</sub> knockouts suggestive of increased spontaneous pain. Interestingly, CB<sub>2</sub>-positive lymphocytes infiltrated the injured nerve and possible CB<sub>2</sub>transfer from immune cells to neurons was found. Lymphocyte CB<sub>2</sub>depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB<sub>2</sub>that protects against spontaneous and evoked neuropathic pain.
Medical subject headings
- Cannabinoid Receptor Agonists
- Cannabinoids
- Neuralgia
- Protective Agents
- Receptors, Cannabinoid