Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat

It has been suggested that administration of a cannabinoid CB, (SR141716A [ N-(piperidin-1-yl)-5-(4-chlorophenyl)-1 phenyl)-4-methyl-1-H-pyrazole-3-car boxamide]) and CB2 (SR144528 {N-[(1S)-endo-1, 3, 3-trimethyl bicyclo [2.2.1 ] heptan-2-yl]-5-(4chloro-3-methylphenyl)- 1 -(4-methylbenzyl)-pyrazole-3-c arboxamide}) receptor antagonists to mice potentiates inflammatory hyperalg esia by removing an endogenous cannabinoid tone. We examined whether the be havioural response to s.c. formalin injection in rats is similarly enhanced . A total of 30 animals received SR141716A (0.5 or 5 mg/kg) or SR144528 (0. 3 or 3 mg/kg) 30 min before 1% formalin. Pain behaviour was quantified usin g the composite weighted pain score technique (CPS-WST0,1,2). An overall CP S-WST0,1,2 was calculated for each phase and groups were compared (analysis of variance). The results obtained in the control group confirmed the char acteristic biphasic behavioural response to formalin injection. None of ant agonist groups had a significant increase in overall CPS-WST0,1,2 compared to the control. Indeed, a significant decrease in CPS-WST0,1,2 scores for b oth phases was detected in most of all of the groups, except SR141716A at 5 mg/kg. Levels of endogenous cannabinoids (anandamide, palmitoylethanolamid e, 2-arachidonylglycerol) were measured from rats hind-paw skin 1 h after s .c. injection of 0.9% saline (100 mu l), 1% (50 mu l), 2.5% (50 mu l) and 5 % (100 mu l) formalin. The concentration of endocannabinoids did not differ between control and formalin-induced inflammation groups. The activity of anandamide amidohydrolase in hind-paw skin also did not change after treatm ent with formalin. In conclusion, cannabinoid antagonists do not enhance fo rmalin-evoked pain behaviour. These results suggest that, in this model, en dogenous cannabinoids do not tonically attenuate inflammatory hyperalgesia. (C) 2000 Elsevier Science B.V. All rights reserved.