Low Dose Morphine Enhances Morphine Antinociception Effects in the Animals Pretreated with Selective and Non-Selective Phosphodiestrase Inhibitors

In this study, we investigated the interactive effects of intraperitoneal (i.p.) injections of three different phosphodiesterase inhibitors (PDEIs) on morphineinduced analgesia in mice using tail-flick method. Subcutaneous administration of morphine (1, 3 and 6 mg/kg) caused significant antinociceptive effects in a dose dependent manner. Administration of pentoxifylline (12.5, 25, 50 and 100 mg/kg, i.p.), milrinone (3 and 4.5 mg/kg, i.p.) and theophylline (25, 50 and 100 mg/kg, i.p.) as selective and non-seletive phosphodiesterase inhibitors induced analgesia in mice. We also examined the antinociceptive effects of these three PDEIs in combination with non-effective dose of morphine (1 mg/kg). These combinations increased analgesia effects compared to the either morphine or respective phosphodiestrase inhibitor groups significantly. Our findings strongly suggest that PDEIs can induce analgesia and potentiate morphine antinociception effect via possible interactions on the same molecular or biochemical pathways.