It has been suggested that administration of a
cannabinoid CB(1) (SR141716A ¿N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide) and CB(2) (
SR144528 ¿N-[(1S)-endo-1, 3, 3-trimethyl bicyclo ¿2.2.1 heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyr azo le- 3-carboxamide¿) receptor antagonists to mice potentiates inflammatory
hyperalgesia by removing an endogenous
cannabinoid tone. We examined whether the behavioural 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 using the composite weighted
pain score technique (CPS-WST(0,1,2)). An overall CPS-WST(0,1,2) was calculated for each phase and groups were compared (analysis of variance). The results obtained in the control group confirmed the characteristic biphasic behavioural response to
formalin injection. None of antagonist groups had a significant increase in overall CPS-WST(0,1,2) compared to the control. Indeed, a significant decrease in CPS-WST(0,1,2) scores for both phases was detected in most of all of the groups, except
SR141716A at 5 mg/kg. Levels of endogenous
cannabinoids (
anandamide,
palmitoylethanolamide, 2-arachidonylglycerol) were measured from rats hind-paw skin 1 h after s.c. injection of
0.9% saline (100 microl), 1% (50 microl), 2. 5% (50 microl) and 5% (100 microl)
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 treatment with
formalin. In conclusion,
cannabinoid antagonists do not enhance
formalin-evoked
pain behaviour. These results suggest that, in this model, endogenous
cannabinoids do not tonically attenuate inflammatory
hyperalgesia.