The antinociceptive effect of the combination of spinal morphine with systemic morphine or buprenorphine

We sought to analyze the mode of interaction of spinal morphine with system ic morphine or buprenorphine, administered in a wide range of antinocicepti ve doses. The study was performed on Sprague-Dawley rats by using a plantar stimulation test and isobolographic and fractional analyses of drug intera ction. The isobolographic and fractional analyses demonstrated that intrath ecal morphine interacted with subcutaneous morphine in a synergistic manner while producing a 50% or 75% antinociceptive effect. The sum of D-75 fract ions was more than that for 50% antinociception, suggesting a less dramatic interaction. The combination with a maximal relative dose of systemic morp hine (0.66:1) showed a maximal degree of supraadditivity. The interaction b etween spinal morphine and systemic buprenorphine was similar to that of mo rphine/morphine, although the supra-additivity was not as pronounced. For t he doses that produced a 50% antinociceptive effect, a synergistic interact ion was observed only for the combination with a morphine/buprenorphine rat io of 1.33:1. When the relative amount of intrathecal morphine was decrease d or increased, the effect became additive. At the doses that produced 75% antinociception, both combinations of morphine and buprenorphine demonstrat ed supraadditive interaction.