THE NONPEPTIDE NK1 RECEPTOR ANTAGONIST SR140333 PRODUCES LONG-LASTING INHIBITION OF NEUROGENIC INFLAMMATION, BUT DOES NOT INFLUENCE ACUTE CHEMONOCICEPTION OR THERMONOCICEPTION IN RATS

In anaesthetized rats, the neurokinin (NK), receptor antagonist SR140333 (10-1000 mu g/kg) stereoselectively inhibited mustard oil-induced plasma protein extravasation in the dorsal skin of the hind paw. After s.c. administration of SR140333, inhibition of plasma protein extravasation was maximal 3 h after injection. A dose of 0.1 mg/kg i.v. or 1.0 mg/kg s.c. produced long-lasting inhibition which was still significant 24 h after treatment. Since systemic administration of SR140333 has been shown to inhibit nociceptive responses in anaesthetized rats, we wanted to evaluate a possible effect of SR140333 on chemo- and thermonociception in conscious rats. SR140333 (100 mu g/kg s.c) did not reduce the behavioral response of rats to the irritant effect of capsaicin in the wiping test, nor did it affect the thermal nociceptive threshold in the plantar test. Furthermore, the decrease in thermal nociceptive threshold which was produced by intraplanter injection of PGE,, and which has been shown to be entirely dependent on capsaicin-sensitive afferents, was not affected by treatment with this NK, receptor antagonist. These results show that systemic administration of SR140333, at doses which cause inhibition of neurogenic inflammation, has no detectable effect on acute chemo- or thermonociception in conscious rats.