The in vivo effect of inhibitors of
fatty acid amide hydrolase (FAAH) upon oedema volume and FAAH activity was evaluated in the
carrageenan induced hind paw
inflammation model in the mouse. Oedema was measured at two time points, 2 and 4 h, after intraplantar injection of
carrageenan to anaesthetised mice. Intraperitoneal (i.p.)
injections of the FAAH inhibitor
URB597 (0.1, 0.3, 1 and 3 mg kg(-1)) 30 min prior to
carrageenan administration, dose-dependently reduced oedema formation. At the 4 h time point, the ED(50) for
URB597 was approximately 0.3 mg kg(-1).
Indomethacin (5 mg kg(-1) i.p.) completely prevented the oedema response to
carrageenan. The antioedema effects of
indomethacin and
URB597 were blocked by 3 mg kg(-1) i.p. of the CB(2) receptor antagonist
SR144528. The effect of
URB597 was not affected by pretreatment with the
peroxisome proliferator-activated receptor gamma antagonist
bisphenol A diglycidyl ether (30 mg kg(-1) i.p.) or the TRPV1 antagonist
capsazepine (10 mg kg(-1) i.p.), when oedema was assessed 4 h after
carrageenan administration. The CB(1) receptor antagonists
AM251 (3 mg kg(-1) i.p.) and
rimonabant (0.5 mg kg(-1) i.p.) gave inconsistent effects upon the antioedema effect of
URB597. FAAH measurements were conducted ex vivo in the paws, spinal cords and brains of the mice. The activities of FAAH in the paws and spinal cords of the inflamed vehicle-treated mice were significantly lower than the corresponding activities in the noninflamed mice. PMSF treatment almost completely inhibited the FAAH activity in all three tissues, as did the highest dose of
URB597 (3 mg kg(-1)) in spinal cord samples, whereas no obvious changes were seen ex vivo for the other treatments. In conclusion, the results show that in mice, treatment with
indomethacin and
URB597 produce SR144528-sensitive anti-inflammatory effects in the
carrageenan model of acute
inflammation.