Michaud J C, Alonso R, Gueudet C, Fournier M, Calassi R, Brelière J C, Le Fur G, Soubrié P
Sanofi Recherche, Montpellier, France.
Fundam Clin Pharmacol. 1998;12(1):88-94. doi: 10.1111/j.1472-8206.1998.tb00929.x.
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 NK1 and NK2 receptor antagonists, SR140333 and SR48968. SR140333 (0.3, 1 and 3 micrograms/kg intravenously [i.v.]) dose-dependently, reversibly and stereoselectively antagonized the increase of contralateral thalamic activity. This compound, when given i.v. (30 micrograms/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 NK1 vs NK2 receptors in nociceptive transmission following trigeminal ganglion stimulation. Taken together, our results indicate that SR140333 could provide a potent drug for the relief of pain occurring under excessive activity of sensory trigeminal fibers.
对C纤维的三叉神经刺激增加了三叉神经尾侧核（NtV）内的c-fos表达和丘脑神经元活动，这两者都反映了伤害性信息的传递。我们研究了选择性NK1和NK2受体拮抗剂SR140333和SR48968对这两种现象的影响。SR140333（0.3、1和3微克/千克静脉注射[i.v.]）剂量依赖性、可逆性且立体选择性地拮抗对侧丘脑活动的增加。该化合物静脉注射（30微克/千克）或口服（10毫克/千克）时，也减少了Fos样免疫反应性细胞的数量，特别是在NtV的内侧和尾侧水平。相比之下，SR48968对丘脑活动或Fos样免疫反应性均未产生任何拮抗作用。数据强烈表明，在三叉神经节刺激后的伤害性传递中，NK1受体比NK2受体更优先参与。综上所述，我们的结果表明，SR140333可能是一种有效的药物，用于缓解感觉三叉神经纤维过度活动时出现的疼痛。
