SYNERGISM BETWEEN MORPHINE WITH FENTANYL IN EXPERIMENTAL MURINE ASSAYS

Opioids are among the most effective pain relievers available; however induced
antinociception has not been extensively studied in different animal pain models. The studies have been conducted with isolated opioids only, but have not been used in combination, as multimodal analgesia. In the present study, the pharmacological interaction of morphine with fentanyl was evaluated in different murine pain models by means of isobolographic analysis. In control animals, morphine and fentanyl produced a dose-related antinociceptive action in the murine assays and comparing the rank of potency was formalin hind paw phase I > formalin phase II > tail flick. The coadministration of morphine with fentanyl, in a fixed relation 1:1 of their ED , produces a synergistic interaction of different magnitude. The study shows that fentanyl is more effective than morphine. This disparity could be explained according to the suggestions that opioids could be acting through other targets either by different binding capacity, by the regulation or activation of non-opioid receptors. Furthermore, coadministration of morphine with fentanyl induces synergism in the murine trials, confirming the antinociceptive and anti-inflammatory capacity of the opioids.