Peer-Reviewed Journal Details
Mandatory Fields
Starowicz, K,Finn, DP,Kendall, D,Alexander, SPH
2017
January
Advances in pharmacology (San Diego, Calif.)
Cannabinoids and Pain: Sites and Mechanisms of Action
Published
Optional Fields
ACID AMIDE HYDROLASE ROSTRAL VENTROMEDIAL MEDULLA RECEPTOR KNOCKOUT MICE RAT SPINAL-CORD STRESS-INDUCED ANALGESIA CENTRAL-NERVOUS-SYSTEM MECHANICALLY-EVOKED-RESPONSES CHRONIC CONSTRICTION INJURY FEAR-CONDITIONED ANALGESIA DYNAMIC-RANGE NEURONS
80
437
475
The endocannabinoid system, consisting of the cannabinoid(1) receptor (CB1R) and cannabinoid(2) 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.
10.1016/bs.apha.2017.05.003
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