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BEHAVIORAL PHARMACOLOGY

Analysis of the Antinociceptive Effect of the Flavonoid Myricitrin: Evidence for a Role of the L-Arginine-Nitric Oxide and Protein Kinase C Pathways

Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, Brazil (F.C.M.); and Departamento de Ciências Fisiológicas (A.P.L., A.R.S.S.), Departamento de Química (M.G.P.), and Departamento de Farmacologia (C.A.L.K., J.B.C.), Universidade Federal de Santa Catarina, Florianópolis, Brazil

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) and PKC 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 E₂. 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.

Address correspondence to: Dr. Adair R. S. Santos, Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900, Florianópolis, SC, Brazil. E-mail: arssantos{at}ccb.ufsc.br