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Canadian Journal of Anesthesia, Vol 43, 975-981, Copyright © 1996 by Canadian Anesthesiologists' Society
ARTICLES |
H Yamaguchi and H Naito
Department of Anesthesiology, University of Tsukuba, Ibaraki, Japan. hyanchi@igaku.md.tsukuba.ac.jp
PURPOSE: This study was conducted to demonstrate if subeffective dose of N omega Nitro L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, interacts with morphine when given intrathecally (IT), epidurally (EP), and intravenously (IV) to produce a synergistic antinociceptive effect in normal rats. 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 degrees 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 micrograms (Mean +/- SEM) and 76.0 +/- 14.5 micrograms), EP (ED50 = 32.6 +/- 2.4 micrograms and 560 +/- 97 micrograms), and IV (ED50 = 563 +/- 71.8 micrograms 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 microgram in IT, 1.18 +/- 0.32 micrograms in EP, and 50.5 +/- 11.4 micrograms in IV groups) (P < 0.01), suggesting a multiplicative interaction of L-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.
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