Comparison of the visceral antinociceptive effects of Spinally administered MPV-2426 (fadolmidine) and clonidine in the rat

Background: The authors determined the visceral antinociceptive effect induced by MPV-2426 (fadolmidine), a selective α 2 -adrenoceptor agonist, in rats with and without inflammation of the colon. They also determined whether the sympathetic nervous system or intact descending pathways are critical for the α 2 -adrenoceptor-induced visceral antinociception. Methods: Spinal neuronal responses evoked by colorectal distension were recorded in pentobarbitone-anesthetized rats. MPV-2426 was administered onto the spinal cord. Clonidine was used as a reference α 2 -adrenoceptor agonist. Inflammation of the colon was induced by turpentine. Sympathectomy was induced by 6-hydroxydopamine. A midthoracic transection of the spinal cord was performed to study the role of descending pathways. Results: Spinal administration of MPV-2426 produced a dose-dependent attenuation of responses evoked by colorectal distension, and this effect was of the same percentual magnitude in inflamed as in noninflamed animals. Clonidine and MPV-2426 induced equipotent visceral antinociception. The effect by spinally administered MPV-2426 was enhanced by a chemical sympathectomy but not influenced by spinal transection. Conclusions: Spinally administered MPV-2426 produces a dose-dependent visceral antinociception as well in animals with an inflammation of the colon as in controls. The visceral antinociceptive effect induced by spinal MPV-2426 is equipotent to that of spinal clonidine. An intact sympathetic nervous system or intact brainstem-spinal pathway is not critical for the MPV-2426-induced visceral antinociception.