Isobolographic analysis of the interaction between epidural sufentanil and bupivacaine in rats

The present study was performed to evaluate the nature of the interaction between epidurally administered sufentanil and bupivacaine in producing antinociception in rats. Rats in which epidural catheters had been inserted received epidural injections with bupivacaine and sufentanil. Nociception was tested by use of the tail-withdrawal reaction (TWR) test and the hot-plate test. Isobolographic analyses were performed with fixed and variable dose ratio treatment schedules based on the ED50s and the highest inactive concentrations of the compounds in both tests. In the TWR test, a synergistic interaction was obtained between the two compounds independent of whether a variable dose ratio regimen (with either 0.08 microgram/rat sufentanil or 80 micrograms/rat bupivacaine as the preset component) or a fixed dose ratio of 1/1,000 sufentanil/bupivacaine (based on the individual ED50s) was used. In the hot-plate test, a synergistic interaction was observed only in the variable dose ratio regimen with 0.08 microgram/rat sufentanil as the preset component and in the fixed dose ratio regimen of 1/1,000 sufentanil/bupivacaine (a ratio based on the ED50 values of the TWR test) but not with a ratio of 1/200, as demonstrated by the ED50s of both drugs in the hot-plate test. The interaction between epidurally administered bupivacaine and sufentanil seems to be synergistic for both tests when variable and fixed dose ratios are used. The synergism could be more easily demonstrated in the TWR test. For drugs with a segmental action, the hot-plate test seems to be less optimal. The necessity of a minimal critical amount of bupivacaine to obtain synergism may have clinical implications.