Involvement of the dopaminergic system in the central orexin-induced antinociceptive action against colonic distension in conscious rats

We have recently demonstrated that orexin acts centrally in the brain to induce antinociceptive action against colonic distension through orexin 1 receptors in conscious rats. Although the dopaminergic system can induce antinociceptive action for somatic pain, the association between changes in the dopaminergic system and visceral pain perception has not been investigated. In the present study, we hypothesized that the dopaminergic system may be involved in visceral nociception, and if so, the dopaminergic system may mediate the orexin-induced visceral antinociception. Visceral sensation was evaluated using the colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats. Intracisternal injection of D1 (SKF38398) or D2 (quinpirole) dopamine receptor agonist increased the threshold volume of colonic distension-induced AWR in a dose-dependent manner. Pretreatment with either the D1 or D2 dopamine receptor antagonist (SCH23390 or sulpiride, respectively) potently blocked the centrally injected orexin-A-induced antinociceptive action against colonic distension. These results suggest for the first time that dopaminergic signaling via D1 and D2 dopamine receptors in the brain may induce visceral antinociception and that the dopaminergic signaling may be involved in the central orexin-induced antinociceptive action against colonic distension.