Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation.
Cannabidiol (CBD), a nonpsychoactive marijuana constituent, was recently shown as an oral antihyperalgesic compound in a rat model of acute inflammation. We examined whether the CBD antihyperalgesic effect could be mediated by cannabinoid receptor type 1 (CB1) or cannabinoid receptor type 2 (CB2) and/or by transient receptor potential vanilloid type 1 (TRPV1). Rats received CBD (10 mg kg(-1)) and the selective antagonists: SR141716 (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) for CB1, SR144528 (N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3 carboxamide) for CB2 and capsazepine (CPZ) for TRPV1 receptors. The intraplantar injection of carrageenan in rats induced a time-dependent thermal hyperalgesia, which peaked at 3 h and decreased at the following times. CBD, administered 2 h after carrageenan, abolished the hyperalgesia to the thermal stimulus evaluated by plantar test. Neither SR141716 (0.5 mg kg(-1)) nor SR144528 (3 and 10 mg kg(-1)) modified the CBD-induced antihyperalgesia; CPZ partially at the lowest dose (2 mg kg(-1)) and fully at the highest dose (10 mg kg(-1)) reversed this effect. These results demonstrate that TRPV1 receptor could be a molecular target of the CBD antihyperalgesic action.
Department of Biotechnology and Bioscience, University of Milan-Bicocca, Piazza della Scienza 2, Milan 20126, Italy. barbara.costa@unimib.it
Barbara
B
Costa
Gabriella
G
Giagnoni
Chiara
C
Franke
Anna Elisa
AE
Trovato
Mariapia
M
Colleoni
D000284:Administration, Oral; D000818:Animals; D001892:Camphanes / Q000008:administration & dosage; D002185:Cannabidiol / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002351:Carrageenan / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy; D007558:Italy; D008297:Male; D010880:Piperidines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology* / Q000627:therapeutic use; D000077285:Rimonabant; D013997:Time Factors
D001892:Camphanes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D011955:Receptors, Drug; C110630:SR 144528; D002185:Cannabidiol; D002351:Carrageenan; C071423:capsazepine; D000077285:Rimonabant; D002211:Capsaicin