title: Peripheral antinociceptive action of mangiferin in mouse models of experimental pain: role of endogenous opioids, K(ATP)-channels and adenosine.
abstract: This study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the underlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail-flick) nociception in mice. Mangiferin at oral doses of 10 to 100 mg/kg evidenced significant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-inflammatory 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 modified 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 significantly 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-flick test models, suggesting that its analgesic effect is only peripheral but not central. The orally administered mangiferin (10-100 mg/kg) was well tolerated and did not impair the ambulation or the motor coordination of mice in respective open-field and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The findings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endogenous opioids, K(ATP)-channels and adenosine receptors.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, 60430-270 Fortaleza, Ceará, Brazil; National Institute of Science and Technology, Institute of Biomedicine of Brazilian Semi-arid, Faculty of Medicine, Federal University of Ceará, 60430-270 Fortaleza, Ceará, Brazil.
authors.forename: Synara C
authors.initials: SC
authors.lastname: Lopes
authors.forename: Ana Virginia L
authors.initials: AV
authors.lastname: da Silva
authors.forename: Bruno Rodrigues
authors.initials: BR
authors.lastname: Arruda
authors.forename: Talita C
authors.initials: TC
authors.lastname: Morais
authors.forename: Jeison Barros
authors.initials: JB
authors.lastname: Rios
authors.forename: Maria Teresa S
authors.initials: MT
authors.lastname: Trevisan
authors.forename: Vietla S
authors.initials: VS
authors.lastname: Rao
authors.forename: Flávia A
authors.initials: FA
authors.lastname: Santos
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D018847:Opioid Peptides / Q000502:physiology*; D010146:Pain / Q000188:drug therapy*; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D018847:Opioid Peptides; D015221:Potassium Channels; D044004:Xanthones; C013592:mangiferin; D000255:Adenosine Triphosphate; D000241:Adenosine
keywords: Mangiferin; Neuro-inflammatory pain; Opioid mechanism; Peripheral antinociception