Leukotrienes reduce nociceptive responses to bradykinin.

The biotransformation of arachidonic acid leads to two important groups of inflammatory mediators, the leukotrienes and the prostaglandins. Hyperalgesic effects have been demonstrated for prostaglandins in a variety of animal models but the effects of leukotrienes on inflammatory pain are less well documented. Using the isolated rabbit ear model of algesia we have shown that perfusion of the ear with the leukotrienes B4, C4 and D4 (10(-8)-10(-7) M) causes a reversible, dose- and time-dependent reduction of the reflex fall in systemic blood pressure and the "head flick" response induced by injection of bradykinin (400 ng), without affecting similar responses induced by the neurotransmitter acetylcholine. The antagonistic effect of leukotrienes on the algesic action of bradykinin could be reversed by the leukotriene antagonist FPL55712 (2 micrograms/ml). This result implies that the leukotrienes may have a desensitizing effect on the nociceptor during an inflammatory response in contrast to the pain threshold-lowering action of the E- and I-type prostaglandins.