Received for publication July 26, 2005.
Revised October 28, 2005.
Accepted for publication October 31, 2005.

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 intraperitoneal (i.p.) or oral (p.o.) route 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. Likewise, 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 PCK and PCK activation by PMA in mice hindpaw. Myricitrin given i.p. also inhibited the mechanical hyperalgesia induced by bradykinin, without affecting similar responses caused by epinephrine and prostaglandin E₂ (PGE₂). 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 pre-treatment of mice with capsaicin and myricitrin antinociceptive effects are not related with 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.

Key words: Antinociception, Flavonoids, Myricitrin, Nitric oxide, Pain, Protein Kinase C