Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation

Abstract

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.

Figures

Figure 1

Effect of SR141716 (0.5 mg kg−1, i.p.) administration on CBD-induced antihyperalgesia 3 h after carrageenan injection into the rat hindpaw. Each point represents the mean±s.e.m. of five rats. ***P<0.001 vs non inflamed; °°°P<0.001 vs inflamed.

Figure 2

Effect of SR144528 (3 and 10 mg kg−1, p.o.) administration on CBD-induced antihyperalgesia 3 h after carrageenan injection into the rat hindpaw. Each point represents the mean±s.e.m. of five rats. ***P<0.001 vs non inflamed; °°°P<0.001 vs inflamed.

Figure 3

Effect of CPZ (2 and 10 mg kg−1, i.p.) administration on CBD-induced antihyperalgesia 3 h after carrageenan injection into the rat hindpaw. Each point represents the mean±s.e.m. of five rats. ***P<0.001,**P<0.01 vs non inflamed; °°°P<0.001,°P<0.05 vs inflamed; ###P<0.001, #P<0.05 vs inflamed/CBD.