EFFECTS OF SR140333, A SELECTIVE NONPEPTIDE NK1 RECEPTOR ANTAGONIST, ON TRIGEMINO-THALAMIC NOCICEPTIVE PATHWAYS IN THE RAT

Trigeminal stimulation of C-fibers increased c-fos expression within t he trigeminal nucleus caudalis (NtV) and thalamic neuronal activity wh ich both reflect the transmission of a nociceptive message. We examine d the effects on both these phenomena of the selective NK1 and NK2 rec eptor antagonists, SR140333 and SR48968. SR140333 (0.3, 1 and 3 mu g/k g intravenously [iv]) dose-dependently, reversibly and stereoselective ly antagonized the increase of contralateral thalamic activity. This c ompound, when given iv (30 mu g/kg) or orally (10 mg/kg), also reduced the number of Fos-like immunoreactive cells particularly at the media l and caudal level of the NtV. In contrast, SR48968 did not exert any antagonistic effect either on thalamic activity or on Fos-like immunor eactivity. Thr data strongly suggest a preferential involvement of NK1 vs NK2 receptors in nociceptive transmission following trigeminal gan glion stimulation. Taken together, our results indicate that SR140333 could provide a potent drug for the relief of pain occurring under exc essive activity of sensory trigeminal fibers. (C) 1998 Elsevier, Paris .