Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain

Autor: Antonio Ferrer-Montiel, David M. Otte, Anne Schmöle, Sami Kummer, Ryszard Przewlocki, David Cabañero, Andreas Zimmer, Agnieszka Wawrzczak-Bargiela, Hector Huerga Encabo, Rafael Maldonado, Angela Ramírez-López, Eva Drews
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Lymphocyte
medicine.medical_treatment
Self Administration
Monocytes
Mice
Random Allocation
neuroimmune interactions
0302 clinical medicine
Cannabinoid receptor type 2
Medicine
Biology (General)
Receptors
Cannabinoid
Mice
Knockout
Neurons
General Neuroscience
Human biology
General Medicine
operant drug self-administration
medicine.anatomical_structure
Nociception
Neuropathic pain
Knockout mouse
lipids (amino acids
peptides
and proteins)
Research Article
QH301-705.5
Science
Protective Agents
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Immune system
Animals
Human Biology and Medicine
mouse
Gene knockout
Cannabinoid Receptor Agonists
neuropathic pain
cannabinoid cb2 receptor
General Immunology and Microbiology
Cannabinoids
business.industry
spontaneous pain
neuronal and lymphocyte cannabinoid receptors
Mice
Inbred C57BL
030104 developmental biology
Neuralgia
Cannabinoid
business
Neuroscience
030217 neurology & neurosurgery
Zdroj: eLife, Vol 9 (2020)
eLife
ISSN: 2050-084X
Popis: 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. This paper was supported by the following grants: European Commission NeuroPain, FP7-602891-2 to Rafael Maldonado. Instituto de Salud Carlos III RTA, RD16/0017/0020/FEDER to Rafael Maldonado. Ministerio de Ciencia, Innovación y Universidades SAF2017-84060-R FEDER to Rafael Maldonado. Generalitat de Catalunya SGR2017-669, ICREA Academia Award 2015 to Rafael Maldonado. Generalitat de Catalunya 2018 FI_B 00207 to Angela Ramírez-López. Polish Ministry of Science and Education 3070/7.PR/2014/2 to Ryszard Przewlocki. Spanish Ministry of Science, Innovation and Universities 2018-097189-B-C21 to Antonio Ferrer-Montiel. Universidad Miguel Hernandez UMH-PAR2019 to Antonio Ferrer-Montiel.
Databáze: OpenAIRE
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