Isobolographic Analysis of the Cutaneous Antinociceptive Interaction Between Bupivacaine Co-Injected with Serotonin in Rats.

BackgroundThe aim of this experiment was to investigate a long-lasting local anesthetic bupivacaine combined with serotonin at inducing cutaneous antinociception.MethodsThe skin antinociception, characterized by an inhibition of the cutaneous trunci muscle reflex (CTMR) following the pinprick on the dorsal skin of rats, was evaluated. The cutaneous antinociceptive effects of bupivacaine alone, serotonin alone, or bupivacaine co-injected with serotonin in a dose-dependent fashion were constructed, while the drug–drug interactions were evaluated by isobologram.ResultsSubcutaneous serotonin, as well as the local anesthetic bupivacaine provoked dose-related cutaneous antinociception. On an equipotent basis (50% effective dose [ED50]), the relative potency was bupivacaine (0.43 [0.37–0.50] μmol)>serotonin (1.27 [1.15–1.40] μmol) (p<0.01). At the equi-anesthetic doses (ED75, ED50 and ED25), the duration of bupivacaine was similar to that of serotonin at producing cutaneous antinociceptive effects. Co-administration of bupivacaine and serotonin displayed a synergistic antinociception.ConclusionsThe preclinical data demonstrated that serotonin is less potent in eliciting cutaneous antinociceptive effects but has the similar duration of action, compared with bupivacaine. We also found a more significant depth of the sensory block with bupivacaine+serotonin than bupivacaine alone.