Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat.
1. The antiinflammatory activity of synthetic cannabinoid nabilone in the rat model of carrageenan-induced acute hindpaw inflammation was compared with that of the endocannabinoid palmitoylethanolamide and the nonsteroidal antiinflammatory drug indomethacin. 2. Preliminary experiments in rats used a tetrad of behavioural tests, specific for tetrahydrocannabinol-type activity in the CNS. These showed that the oral dose of nabilone 2.5 mg kg(-1) had no cannabinoid psychoactivity. 3. Intraplantar injection of carrageenan (1% w v(-1)) elicited a time-dependent increase in paw volume and thermal hyperalgesia. 4. Nabilone (0.75, 1.5, 2.5 mg kg(-1), p.o.), given 1 h before carrageenan, reduced the development of oedema and the associated hyperalgesia in a dose-related manner. Nabilone 2.5 mg kg(-1), palmitoylethanolamide 10 mg kg(-1) and indomethacin 5 mg kg(-1), given p.o. 1 h before carrageenan, also reduced the inflammatory parameters in a time-dependent manner. 5. The selective CB(2) cannabinoid receptor antagonist [N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3 carboxamide] (SR 144528), 3 mg kg(-1) p.o. 1 h before nabilone and palmitoylethanolamide, prevented the anti-oedema and antihyperalgesic effects of the two cannabinoid agonists 3 h after carrageenan. 6. Our findings show the antiinflammatory effect of nabilone and confirm that of palmitoylethanolamide indicating that these actions are mediated by an uncharacterized CB(2)-like cannabinoid receptor.
Conti
Silvia
S
Department of Biotechnology and Bioscience, Faculty of Sciences, University of Milan-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.
Costa
Barbara
B
Colleoni
Mariapia
M
Parolaro
Daniela
D
Giagnoni
Gabriella
G
D000208:Acute Disease; D000577:Amides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001892:Camphanes / Q000494:pharmacology / Q000627:therapeutic use; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan / Q000008:administration & dosage; D004195:Disease Models, Animal; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D063388:Endocannabinoids; D004983:Ethanolamines; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010169:Palmitic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors
C113759:1',1'-dimethylheptyl-delta(8)-tetrahydrocannabinol-11-oic acid; D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001892:Camphanes; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C110630:SR 144528; C011941:nabilone; C005958:palmidrol; D013759:Dronabinol; D002351:Carrageenan; D007213:Indomethacin