Synergistic antinociception of propofol-alfentanil combination in mice

Drug combination is frequently used in pain treatment, which can produce similar analgesia with reduced dosage and side effects. In the present study, we examined the effects of co-administration of propofol, a general anesthetic, and alfentanil, an opioid analgesic drug, and the types of interactions between them in heat induced acute phasic and acetic-acid induced acute tonic pain models using the up-and-down method. In both pain models, alfentanil was administered in fixed-dose fractions of the 50% effective dose (ED50), and the types of interactions were determined by isobolographic analysis. In hot plate test, alfentanil (35.6-50.0 μg/kg, i.v.), propofol (6.5-15.5mg/kg, i.v.), and their combinations (80%, 50%, 30% and 10% of a single drug ED50) produce a significant, dose-dependent antinociception. In the tail-flick test, alfentanil (35.6-50.0 μg/kg, i.v.), propofol (5.0-14.3mg/kg, i.v.), and their combination significantly and dose dependently extend the tail-flick latency. In the acetic-acid induced writhing test, alfentanil (12.5-23.2 μg/kg, i.p.), propofol (15.0-28.5mg/kg, i.p.), and their combination significantly and dose dependently reduce the frequency of writhing. In all the above pain models, isobolographic analysis revealed a significant synergistic interaction between alfentanil and propofol, with about 4-fold reduction of doses of both drugs, in comparison with each single drug's ED50. These data suggest that the combination of alfentanil and propofol synergistically suppresses acute phasic and tonic pain in mice, indicating a potential application in pain treatment.