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Antinociceptive synergistic interaction between morphine and nω-nitro 1-arginine methyl ester on thermal nociceptive tests in the rats

1996; Springer Science+Business Media; Volume: 43; Issue: 9 Linguagem: Inglês

10.1007/bf03011815

1496-8975

Hiroshi Yamaguchi, Hiroshi Naito,

Pharmacological Receptor Mechanisms and Effects

This study was conducted to demonstrate if subeffective dose of Nω Nitro L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, interacts with morphine when given intrathecaly (IT), epidurally (EP), and intravenously (IV) to produce a synergistic antinociceptive effect in normal rats. 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. 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 ± 71.8μ 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 TV groups) (P < 0.01), suggesting a multiplicative interaction of L-NAME with morphine. L-NAME has a synergistic antinociceptive interaction with morphine in response to thermal stimulation when given intrathecally, epidurally or intravenously in rats.