Mechanisms involved in the antinociceptive effects of 7-hydroxycoumarin.

Abstract

7-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 E(2) (PGE(2)), suggesting that it acts upstream of PGE(2.) 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 PGE(2), 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 PGE(2) production and are supportive of the further investigation of the therapeutic potential of 1 to control inflammatory pain.

• Authors: Flávia 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
• Journal: Journal of natural products (J Nat Prod) Vol. 74 Issue 4 Pg. 596-602 (Apr 25 2011) ISSN: 1520-6025 [Electronic] United States
• PMID: 21417376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Tumor Necrosis Factor-alpha
• Umbelliferones
• 7-hydroxycoumarin
• Freund's Adjuvant
• Dinoprostone

Topics

• Analgesics (chemistry, metabolism, pharmacology, therapeutic use)
• Animals
• Brazil
• Dinoprostone (pharmacology)
• Edema (chemically induced, drug therapy)
• Freund's Adjuvant (pharmacology)
• Mice
• Models, Animal
• Molecular Structure
• Neutrophils (drug effects, physiology)
• Pain (chemically induced, drug therapy)
• Pain Measurement
• Tumor Necrosis Factor-alpha (pharmacology)
• Umbelliferones (chemistry, pharmacology, therapeutic use)