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Adv Pharmacol. 2017;80:437-475. doi: 10.1016/bs.apha.2017.05.003. Epub 2017 Jun 20.

Cannabinoids and Pain: Sites and Mechanisms of Action.

Author information

1
Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pain Pathophysiology, Krakow, Poland.
2
Pharmacology and Therapeutics, School of Medicine, Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland, Galway, Ireland. Electronic address: david.finn@nuigalway.ie.

Abstract

The endocannabinoid system, consisting of the cannabinoid1 receptor (CB1R) and cannabinoid2 receptor (CB2R), endogenous cannabinoid ligands (endocannabinoids), and metabolizing enzymes, is present throughout the pain pathways. Endocannabinoids, phytocannabinoids, and synthetic cannabinoid receptor agonists have antinociceptive effects in animal models of acute, inflammatory, and neuropathic pain. CB1R and CB2R located at peripheral, spinal, or supraspinal sites are important targets mediating these antinociceptive effects. The mechanisms underlying the analgesic effects of cannabinoids likely include inhibition of presynaptic neurotransmitter and neuropeptide release, modulation of postsynaptic neuronal excitability, activation of the descending inhibitory pain pathway, and reductions in neuroinflammatory signaling. Strategies to dissociate the psychoactive effects of cannabinoids from their analgesic effects have focused on peripherally restricted CB1R agonists, CB2R agonists, inhibitors of endocannabinoid catabolism or uptake, and modulation of other non-CB1R/non-CB2R targets of cannabinoids including TRPV1, GPR55, and PPARs. The large body of preclinical evidence in support of cannabinoids as potential analgesic agents is supported by clinical studies demonstrating their efficacy across a variety of pain disorders.

KEYWORDS:

Brain; Cannabinoid receptor; Endocannabinoids; In vivo; Mouse; Pain; Periphery; Preclinical; Rat; Spinal cord

PMID:
28826543
DOI:
10.1016/bs.apha.2017.05.003
[Indexed for MEDLINE]

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