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Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation Costa B; Giagnoni G; Franke C; Trovato AE; Colleoni MBr J Pharmacol 2004[Sep]; 143 (2): 247-50Cannabidiol (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.|*Disease Models, Animal[MESH]|Administration, Oral[MESH]|Animals[MESH]|Camphanes/administration & dosage[MESH]|Cannabidiol/antagonists & inhibitors/pharmacology/*therapeutic use[MESH]|Capsaicin/*analogs & derivatives/pharmacology/therapeutic use[MESH]|Carrageenan/adverse effects[MESH]|Dose-Response Relationship, Drug[MESH]|Drug Evaluation, Preclinical/methods[MESH]|Drug Therapy, Combination[MESH]|Hyperalgesia/chemically induced/*drug therapy/physiopathology[MESH]|Inflammation/*chemically induced/drug therapy[MESH]|Italy[MESH]|Male[MESH]|Piperidines/administration & dosage[MESH]|Pyrazoles/administration & dosage[MESH]|Rats[MESH]|Rats, Wistar[MESH]|Receptor, Cannabinoid, CB1/administration & dosage/antagonists & inhibitors[MESH]|Receptor, Cannabinoid, CB2/administration & dosage/antagonists & inhibitors[MESH]|Receptors, Drug/drug effects/*physiology/therapeutic use[MESH]|Rimonabant[MESH]|Time Factors[MESH] |
