Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain
- Universitat Pompeu Fabra, Spain
- University of Bonn, Germany
- Polish Academy of Sciences, Poland
- Universidad Miguel Hernández, Spain
Abstract
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.
Data availability
All experimental data and statistical analyses of this study are included in the manuscript and its supplementary files. Raw data and results of statistical analyses are provided in the Source Data File and its containing data sheets.
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Author details
Funding
European Commission (FP7-602891-2)
- Rafael Maldonado
Instituto de Salud Carlos III (RD12/0028/0023/FEDER)
- Rafael Maldonado
Ministerio de Economía y Competitividad (SAF2014-59648-P)
- Rafael Maldonado
Generalitat de Catalunya (2014-SGR-1547)
- Rafael Maldonado
Generalitat de Catalunya (2018 FI_B 00207)
- Angela Ramírez-López
Polish Ministry of Science and Education (3070/7.PR/2014/2)
- Ryszard Przewlocki
Universidad Miguel Hernandez (UMH-PAR2019)
- Antonio Ferrer-Montiel
Spanish Ministry of Science, Innovation and Universities (RTI2018-097189-B-C21)
- Antonio Ferrer-Montiel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal handling and experiments were in accordance with protocols approved by the respective Animal Care and Use Committees of the PRBB, Departament de Territori i Habitatge of Generalitat de Catalunya and the Institute of Molecular Psychiatry and were performed in accordance with the European Communities Council Directive (2010/63/EU).
Copyright
© 2020, Cabañero et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain
eLife 9:e55582.
https://doi.org/10.7554/eLife.55582
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