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

In anaesthetized rats, the neurokinin (NK), receptor antagonist SR1403 33 (10-1000 mu g/kg) stereoselectively inhibited mustard oil-induced p lasma protein extravasation in the dorsal skin of the hind paw. After s.c. administration of SR140333, inhibition of plasma protein extravas ation 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 significa nt 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 thermo nociception in conscious rats. SR140333 (100 mu g/kg s.c) did not redu ce the behavioral response of rats to the irritant effect of capsaicin in the wiping test, nor did it affect the thermal nociceptive thresho ld in the plantar test. Furthermore, the decrease in thermal nocicepti ve 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 antago nist. These results show that systemic administration of SR140333, at doses which cause inhibition of neurogenic inflammation, has no detect able effect on acute chemo- or thermonociception in conscious rats.