Intrathecal clonidine and bupivacaine have synergistic analgesia for acute thermally or inflammatory-induced pain in rats

We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain. Rats implanted with lumbar intrathecal catheters were injected intrathecally with saline (control), bupivacaine (1 to 100 mug), or clonidine (0.1 to 3 mug) and tested for their responses to thermal stimulation to the tail (tail flick test) and subcutaneous formalin injection into the hindpaw (formalin test). The effects of the combination of bupivacaine and clonidine on both stimuli were tested by isobolographic analysis. General behavior and motor function were examined as side effects. The 50% effective doses of bupivacaine and clonidine were significantly smaller when combined compared with each single drug in both the tail flick test (2.82 and 0.11 mug versus 7.1 and 0.29 mug, respectively) and phase 1 (0.24 and 0.009 mug versus 5.7 and 0.15 mug) and phase 2 (0.31 and 0.012 mug versus 3.2 and 0.16 mug) of the formalin test. Side effects were decreased by the combination. These results suggest a favorable combination of intrathecal bupivacaine and clonidine in the management of acute and inflammatory pain.