Additivity of bupivacaine and morphine for peripheral analgesia in rats

Infiltration of the surgical wound is a classical technique for post-operative analgesia. Recent studies have suggested that local anaesthetic may be combined with other drugs such as opioids. This study has evaluated, in rat, the infiltration with morphine, bupivacaine and their combination. In all groups, the two hind paws were injected with carrageenin. The left hind paw was used as control. The vocalisation threshold to paw pressure (VTPP) of both hind paws was evaluated 2 h after induction of carrageenin inflammation (baseline value), then every 10 min until the return to baseline value after injection of analgesic drugs. The development of oedema was evaluated in both hind paws by measurement of paw circumference (PC) before, then after, carrageenin injection. All analgesic drugs were injected in the right inflamed paw diluted in 0.2 mL of normal saline. The analgesic effect of bupivacaine (0.1, 0.25 and 0.5%), morphine (25, 50 and 100 microg) and their combination (bupivacaine 0.1%/morphine 20 microg, bupivacaine 0.2%/morphine 40 microg and bupivacaine 0.4%/morphine 80 microg) was tested. The effect of naloxone on morphine induced analgesia was tested. The interaction between bupivacaine and morphine was evaluated with an isobolographic analysis. Bupivacaine produced a dose-dependent antinociceptive effect. Morphine infiltration produced a peripheral, dose-dependent analgesic effect antagonised by naloxone. This analgesic effect of morphine was associated with an anti-inflammatory effect. The isobolographic analysis revealed only additivity between bupivacaine and morphine. The infiltration with morphine offers a peripheral analgesic effect which is additive with the effect of bupivacaine. An anti-inflammatory effect of morphine participates in this peripheral analgesic effect.