Produção Nacional
Revisado por pares
Mechanisms Involved in the Antinociceptive Effects of 7-Hydroxycoumarin
2011; American Chemical Society; Volume: 74; Issue: 4 Linguagem: Inglês
10.1021/np100621c
ISSN1520-6025
AutoresFlávia Oliveira de Lima, Fabiana Regina Nonato, Ricardo David Couto, José Maria Barbosa‐Filho, Xirley Pereira Nunes, Ricardo Ribeiro dos Santos, Milena Botelho Pereira Soares, Cristiane Flora Villarreal,
Tópico(s)Bioactive Compounds and Antitumor Agents
Resumo7-Hydroxycoumarin (umbelliferone, 1), the main metabolite of coumarin, has been reported to produce potent antinociceptive effects in animal models of pain. However, the biochemical events involved in antinociception mediated by 1 are currently not well understood. In the present study, the mechanisms by which 1 exerts its pharmacological actions were investigated. Acute pretreatment of mice with 1 produced a long-lasting antinociceptive effect against complete Freund's adjuvant (CFA)-induced hyperalgesia. The subchronic administration of 1 inhibited CFA-induced hyperalgesia and paw edema, while it did not cause any apparent toxicity. Another set of experiments showed that 1 inhibited carrageenan-induced mechanical hyperalgesia, but not mechanical hyperalgesia induced by prostaglandin E2 (PGE2), suggesting that it acts upstream of PGE2. Treatment with 1 was able to prevent the plantar tissue neutrophil influx induced by local inflammatory stimuli. In addition, 1 exhibited inhibitory effects on the release of hyperalgesic cytokines (TNF-α and IL-1β) and the production of PGE2, a directly acting hyperalgesic mediator. The present results suggest that the antinociceptive effect of 1 is correlated with the inhibition of neutrophil migration, cytokine release, and PGE2 production and are supportive of the further investigation of the therapeutic potential of 1 to control inflammatory pain.
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