Comparative somatic and visceral antinociception and neurotoxicity of intrathecal bupivacaine, levobupivacaine, and dextrobupivacaine in rats

Abstract

BACKGROUND: The current study investigated whether racemic bupivacaine and its S(-)- and R(+)-enantiomers, levobupivacaine and dextrobupivacaine, differ in somatic and visceral antinociception and neurotoxicity when administered intrathecally in rats. METHODS: In experiment 1, rats intrathecally received 15 μl saline or 0.125, 0.25, 0.5, or 1% bupivacaine, levobupivacaine, or dextrobupivacaine. The tail-flick and colorectal distension tests were performed to assess somatic and visceral antinociceptive effects, respectively, for 180 min after injection. In experiment 2, rats given 0.25% anesthetic solutions were evaluated with colorectal distension-induced response in blood pressure and heart rate. In experiment 3, four groups of rats received a 1-h infusion of saline or 2.5% bupivacaine, levobupivacaine, or dextrobupivacaine. Additional rats received either 1.25% bupivacaine or levobupivacaine for 1 h. Four days after infusion, animals were assessed for persistent sensory impairment using the tail-flick test. Spinal cords and nerve roots were obtained for histologic analysis. RESULTS: In experiment 1, the three drugs produced similar time course effects and dose-effect relations in tail-flick latency. Colorectal distension thresholds and motor paralysis were slightly lower and less apparent, respectively, at some concentrations in rats given levobupivacaine than in those given the other agents. In experiment 2, colorectal distension-induced response in heart rate was less depressed in rats given levobupivacaine than in those given the other anesthetics. In experiment 3, three groups of rats given 2.5% anesthetic solutions developed similar significant increases in tail-flick latency and incurred similar morphologic damage. Two groups of rats receiving 1.25% anesthetic solutions were similar in functional impairment and nerve injury scores. CONCLUSIONS: The results suggest that, when administered intrathecally in rats, bupivacaine and its R(+)- and S(-)-enantiomers are similar for somatic antinociception and neurotoxicity but slightly different in visceral antinociception and motor paralysis, in which levobupivacaine is less potent than the others. © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.