کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2494871 | 1115583 | 2008 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain](/preview/png/2494871.png)
The antinociceptive effects of the endocannabinoids (ECs) are enhanced by inhibiting catabolic enzymes such as fatty acid amide hydrolase (FAAH). The physiological relevance of the metabolism of ECs by other pathways, such as cyclooxygenase-2 (COX2) is less clear. To address this question we compared the effects of local inhibition of FAAH versus COX2 (URB597 and nimesulide, respectively) on inflammatory hyperalgesia and levels of endocannabinoids and related molecules in the hindpaw.Inflammatory hyperalgesia was measured following intraplantar injection of carrageenan. Effects of intraplantar injection of URB597 (25 μg and 100 μg) or nimesulide (50 μg) on hyperalgesia and hindpaw levels of anandamide (AEA), 2-arachidonoylglycerol (2AG) and N-palmitoylethanolamine (PEA) were determined.Although both doses of URB597 increased levels of AEA and 2AG in the carrageenan inflamed hindpaw, only the lower dose of URB597 attenuated hyperalgesia (P < 0.05). Nimesulide attenuated both hyperalgesia and hindpaw oedema (P < 0.001, P < 0.01, respectively) and increased levels of PEA (P < 0.05) in the hindpaw. Since both AEA and PEA are ligands for peroxisome proliferator-activated receptor-alpha (PPARα), the effects of the PPARα antagonist GW6471 on nimesulide- and URB597-mediated effects were studied. GW6471, but not a PPARγ antagonist, blocked the inhibitory effects of nimesulide and URB597 on hyperalgesia.Our data suggest that both COX2 and FAAH play a role in the metabolism of endocannabinoids and related molecules. The finding that PPARα antagonism blocked the inhibitory effects of nimesulide and URB597 suggests that PPARα contributes to their antinociceptive effects in the carrageenan model of inflammatory hyperalgesia.
Journal: Neuropharmacology - Volume 55, Issue 1, July 2008, Pages 85–93