Mechanisms underlying the antinociceptive effect of mangiferin in the formalin test.

Abstract The purpose of this study was to investigate the possible antinociceptive effect of mangiferin, a glucosylxanthone present in Mangifera indica L., in inflammatory pain. Furthermore, we sought to investigate the possible mechanisms action that contributes to these effects. The ipsilateral local peripheral (1–30 µg/paw), intrathecal (1–30 µg/rat) and oral (1–30 mg/kg) administration of mangiferin produced a dose-dependent reduction in formalin-induced nociception. The antinociceptive effect of this drug was similar to that induced by diclofenac after oral and local peripheral administration. Furthermore, mangiferin was also able to reduce 0.1% capsaicin- and serotonin-induced nociceptive behavior. The local peripheral antinociceptive effect of mangiferin in the formalin test was blocked by naloxone (50 μg/paw), naltrindole (1 μg/paw), 5-guanidinonaltrindole (5-GNTI, 1 μg/paw), N G - l -nitro-arginine methyl ester (L-NAME, 100 µg/paw), 1 H -(1,2,4)-oxadiazolo [4,2- a ]quinoxalin-1-one (ODQ, 50 µg/paw) and glibenclamide (50 μg/paw), but not by methiothepin (30 μg/paw). These results suggest that the antinociceptive effects induced by mangiferin are mediated by the peripheral opioidergic system involving the activation of δ , κ , and probably µ , receptors, but not serotonergic receptors. Data also suggests that mangiferin activates the NO–cyclic GMP-ATP-sensitive K + channels pathway in order to produce its local peripheral antinociceptive effect in the formalin test. Mangiferin may prove to be effective in treating inflammatory pain in humans.