Antinociceptive synergistic interaction between morphine and n(ω)-nitro l-arginine methyl ester on thermal nociceptive tests in the rats

Abstract

Methods: Chronically catheterized 72 male Wistar rats were used in this study. We measured the tail flick latency in response to thermal stimulation of the tail on a hot plate (53°C), and determined dose-response functions of IT, EP and IV morphine, L-NAME, and morphine co-administered with subeffective doses of L-NAME. The antinociceptive effect was evaluated using the doses for 50% maximum probable effect (ED50). The interaction between morphine and L-NAME was evaluated using an isobolographic approach. ANOVA was used for the statistical analysis. Significance was taken at P < 0.05. Results: Morphine and L-NAME produced dose-related antinociceptive effects in the IT (ED50 = 1.23 ± 0.18 μg (Mean ± SEM) and 76.0 ± 14.5 μg), EP (ED50 = 32.6 ± 2.4 μg and 560 ± 97 μg), and IV (ED50 = 563 ± 71.8 μg and 16.0 ± 4.0 mg) groups, respectively. Co-administration of small doses of L-NAME and morphine produced reductions in the ED50 values for morphine (0.16 ± 0.03 μg in IT, 1.18 ± 0.32 μg in EP, and 50.5 ± 11.4 μg in IV groups) (P < 0.01), suggesting a multiplicative interaction oft-NAME with morphine. Conclusion: L-NAME has a synergistic antinociceptive interaction with morphine in response to thermal stimulation when given intrathecally, epidurally or intravenously in rats.