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

ELife
David CabañeroRafael Maldonado

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.

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Citations

Dec 30, 2020·International Journal of Molecular Sciences·Qing-Rong LiuEmmanuel S Onaivi
Dec 31, 2020·International Journal of Molecular Sciences·Joanna Agnieszka Komorowska-Müller, Anne-Caroline Schmöle
Apr 29, 2021·European Journal of Pain : EJP·David Cabañero, Rafael Maldonado
Jun 22, 2021·Neuropharmacology·Alejandra Escudero-LaraRafael Maldonado
Aug 24, 2021·Expert Opinion on Therapeutic Targets·David CabañeroRafael Maldonado

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Methods Mentioned

BETA
pharmacotherapy
flow cytometry
electrophoresis
PCR
Fluorescence

Software Mentioned

Otsu
Fiji
Leica Application Suite Advanced Fluorescence
CFX MANAGER
SPSS
STATISTICA
FACSDiva

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