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Background: There is some evidence of antinociceptive effect of hydroalcoholic extract of Apium graveolens fruits in some recent studies. In present study, the possible mechanism of this effect of extract has been evaluated. Materials and Methods: In this experimental study, 48 male mice were examined. To evaluate the antinociceptive effect of extract, formalin test was used. The possible mechanism of extract was investigated with interaction of 3 drugs [Naloxone (2mg/kg), Dextromethorphan (20 mg/kg), L-NAME (20 mg/kg)] and Hydroalcoholic extract of apium graveolens fruits.(400 mg/kg) Results: Administration of Naloxone had no effect on antinociception of Hydroalcoholic extract of apium graveolens fruits. There was no significant difference between Dextromethorphan Plus extract and extract group in first phase. Pretreatment with L-NAME, decreased antinociceptive effect of extract in second phase of formalin test(p<0.05) Conclusion: Dextromethorphan has analgesic effect in acute phase and its interaction with hydroalcoholic extract of apium graveolens fruits shows at least, part of antinoceceptive effect of extract is via NMDA receptors in acute phase. On the other hand, it seems part of antinoceceptive effect of extract is via inhibition of NO syntheses in chronic phase. Extract of Apium graveolens may be effect via other neural pathways such as dopamine, noradrenalin or serotonin that need more research.

Keywords: Apium graveolens, Dextromethorphan, L-NAME, extract, Mice

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