Dynamic regulation of the endocannabinoid system: implications for analgesia.
The analgesic effects of cannabinoids are well documented, but these are often limited by psychoactive side-effects. Recent studies indicate that the endocannabinoid system is dynamic and altered under different pathological conditions, including pain states. Changes in this receptor system include altered expression of receptors, differential synthetic pathways for endocannabinoids are expressed by various cell types, multiple pathways of catabolism and the generation of biologically active metabolites, which may be engaged under different conditions. This review discusses the evidence that pain states alter the endocannabinoid receptor system at key sites involved in pain processing and how these changes may inform the development of cannabinoid-based analgesics.
Sagar
Devi Rani
DR
School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK. devi.sagar@nottingham.ac.uk
Gaw
A Gemma
AG
Okine
Bright N
BN
Woodhams
Stephen G
SG
Wong
Amy
A
Kendall
David A
DA
Chapman
Victoria
V
D000581:Amidohydrolases / Q000378:metabolism; D000698:Analgesia; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis / Q000378:metabolism*; D002186:Cannabinoids / Q000378:metabolism; D063388:Endocannabinoids; D006801:Humans; D010146:Pain / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D047492:Peroxisome Proliferator-Activated Receptors; D000099252:Fatty Acid Amide Hydrolases