Midazolam can potentiate the analgesic effects of intrathecal bupivacaine on thermal- or inflammatory-induced pain.

Epidurally administered midazolam can potentiate analgesia by epidural bupivacaine. However, whether this effect is synergistic or additive is not known. In this study, we investigated the spinally-mediated analgesic interaction between midazolam and bupivacaine by using the tail-flick and formalin tests in rats with chronically implanted catheters. Behavioral effects were also observed. The dose dependency of analgesia and the 50% effective doses of intrathecal midazolam and bupivacaine were determined, and then the interaction of these two drugs was examined with an isobolographic analysis. Both drugs had dose-dependent analgesic effects in both the tail-flick test and the formalin test. The 50% effective dose values of the combination were significantly lower than the calculated additive values in both tests (P = 0.023 in the tail-flick test; P = 0.0025 in Phase 1 and 0.047 in Phase 2 of the formalin test). Behavioral side effects decreased in the combination group compared with each drug alone. In conclusion, intrathecally administered midazolam and bupivacaine had synergistic analgesic effects on acute thermal- or inflammatory-induced pain, with decreased behavioral side effects. In both acute thermal- and inflammatory-induced pain, intrathecally administered midazolam and bupivacaine produced synergistic analgesia with decreased side effects in intrathecally catheterized rats.