Rotigotine-loaded microspheres exerts the antinociceptive effect via central dopaminergic system

Rotigotine-loaded microspheres (RoMS), a sustained-release formulation with a continuous release of rotigotine for more than 7 days in vivo, have been conducted a clinical trial for the treatment of Parkinson's disease (PD). Previous work from our laboratory showed that RoMS exerted an antinociceptive effect in rat models of inflammatory pain. The purpose of this study was to investigate the mechanisms of action underlying the antinociceptive effect of RoMS. A rat model of inflammatory pain was prepared by an intraplantar injection of carrageenan. The hot plate test and the Randall-Selitto test were used to evaluate the effect of domperidone (selective D₂ receptor antagonist), D₂D₃ shRNA, and naloxone (nonselective opioid receptor antagonist) on RoMS-mediated antinociceptive efficacy. The expressions of D₂ and D₃ receptors in the striatum and periaqueductal gray were measured by Western blotting. Intracerebroventricular injection of domperidone abated the antinociceptive effect of RoMS. However, intraperitoneal injection of domperidone had no significant effect on the antinociceptive action of RoMS. Intracerebroventricular injection with D₂D₃ shRNA significantly attenuated the expressions of D₂ and D₃ receptors in the striatum and the periaqueductal gray. D₂ and D₃ receptors silence significantly weakened RoMS-mediated antinociceptive effect. Intracerebroventricular injection of naloxone also alleviated the antinociceptive effect of RoMS. The results suggest that RoMS-mediated antinociceptive efficacy is associated with activating central dopamine D₂ and D₃ receptors. Opioid receptors play a role in the antinociceptive effect of RoMS.