Effects of SR140333, a selective non-peptide NK1 receptor antagonist, on trigemino-thalamic nociceptive pathways in the rat
1998
Trigeminal stimulation of C-fibers increased c-fos expression within the trigeminal nucleus caudalis (NtV) and thalamic neuronal activity which both reflect the transmission of a nociceptive message. We examined the effects on both these phenomena of the selective NK 1 and NK 2 receptor antagonists, SR140333 and SR48968. SR140333 (0.3, 1 and 3 μg/kg intravenously [iv]) dose-dependently, reversibly and stereoselectively antagonized the increase of contralateral thalamic activity. This compound, when given iv (30 μg/kg) or orally (10 mg/kg), also reduced the number of Fos-like immunoreactive cells particularly at the medial and caudal level of the NtV. In contrast, SR48968 did not exert any antagonistic effect either on thalamic activity or on Fos-like immunoreactivity. The data strongly suggest a preferential involvement of NK 1 vs NK 2 receptors in nociceptive transmission following trigeminal ganglion stimulation. Taken together, our results indicate that 5R140333 could provide a potent drug for the relief of pain occurring under excessive activity of sensory trigeminal fibers.
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