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) α and PKCϵ 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.
Footnotes
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This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, the Programa de Apoio aos Núcleos de Excelência, and the Fundação de Apoio a Pesquisa Científica e Tecnológica do Estado de Santa Catarina, Brazil.
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doi:10.1124/jpet.105.092825.
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ABBREVIATIONS: NO, nitric oxide; i.pl., intraplantar(ly); PMA, phorbol 12-myristate 13-acetate; l-NOARG, Nω-nitro-l-arginine; PKC, protein kinase C; PBS, phosphate-buffered saline; ANOVA, analysis of variance; PGE2, prostaglandin E2; PKA, protein kinase A; TRPV1, transient receptor potential vanilloid type 1.
- Received July 25, 2005.
- Accepted October 31, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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