Peripheral antinociceptive action of mangiferin in mouse models of experimental pain : role of endogenous opioids, K ATP -channels and adenosine

Abstract

his study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the un- derlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail- fl ick) nociception in mice. Mangiferin at oral doses of 10 to 100 mg/kg evidenced signif- icant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-in fl ammatory pain, in a naloxone-sensitive manner, suggesting the participation of endogenous opiates in its mechanism. In capsaicin test, the antinociceptive effect of mangiferin (30 mg/kg) was not modi fi ed by respective competitive and non-competitive transient receptor potential vanilloid 1 (TRPV1) antagonists, capsazepine and ruthenium red, or by pretreatment with L -NAME, a non-selective nitric oxide synthase inhibitor, or by ODQ, an inhibitor of soluble guanylyl cyclase. However, mangiferin effect was signi fi cantly reversed by glibenclamide, a blocker of K ATP channels and in animals pretreated with 8-phenyltheophylline, an adenosine receptor antagonist. Mangiferin failed to modify the thermal nociception in hot-plate and tail- fl ick test models, suggesting that its analgesic effect is only periph- eral but not central. The orally administered mangiferin (10 – 100 mg/kg) was well tolerated and did not im- pair the ambulation or the motor coordination of mice in respective open- fi eld and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The fi ndings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endoge- nous opioids, K ATP -channels and adenosine receptors