title: Analysis of the antinociceptive effect of the flavonoid myricitrin: evidence for a role of the L-arginine-nitric oxide and protein kinase C pathways.
abstract: The present study investigated the antinociceptive effects of the flavonoid myricitrin in chemical behavioral models of pain in mice and rats. Myricitrin given by i.p. or p.o. routes produced dose-related antinociception when assessed on acetic acid-induced visceral pain in mice. In addition, the i.p. administration of myricitrin exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin. Like-wise, myricitrin given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). Western blot analysis revealed that myricitrin treatment fully prevented the protein kinase C (PKC) alpha and PKCepsilon activation by PMA in mice hind paws. Myricitrin given i.p. also inhibited the mechanical hyperalgesia induced by bradykinin, without affecting similar responses caused by epinephrine and prostaglandin E(2). The antinociception caused by myricitrin in the acetic acid test was significantly attenuated by i.p. treatment of mice with the nitric oxide precursor, L-arginine. In contrast, myricitrin antinociception was not affected by naloxone (opioid receptor antagonist) or neonatal pretreatment of mice with capsaicin and myricitrin antinociceptive effects is not related to muscle relaxant or sedative action. Together, these results indicate that myricitrin produces pronounced antinociception against chemical and mechanical models of pain in rodents. The mechanisms involved in their actions are not completely understood but seem to involve an interaction with nitric oxide-L-arginine and protein kinase C pathways.
authors.affiliation: Departamento de Química, Universidade Federal de Santa Maria, Brazil.
authors.forename: Flavia Carla
authors.initials: FC
authors.lastname: Meotti
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Luiz
authors.forename: Moacir Geraldo
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: Cândida A L
authors.initials: CA
authors.lastname: Kassuya
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018712:Analgesics, Non-Narcotic; D005419:Flavonoids; D009569:Nitric Oxide; C008577:myricitrin; D001120:Arginine; D011493:Protein Kinase C