Mechanisms Involved in the Antinociceptive Effects of 7-Hydroxycoumarin
Mechanisms Involved in the Antinociceptive Effects of 7-Hydroxycoumarin
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DOI：
10.1021/np100621c
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发表时间：
2011-04-01
影响因子：
5.1
通讯作者：
Villarreal, Cristiane Flora
中科院分区：
文献类型：
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作者：
de Lima, Flavia Oliveira;Nonato, Fabiana Regina;Villarreal, Cristiane Flora
7-羟基香豆素（伞形酮，1）：香豆素的主要代谢产物，已被报道在疼痛的动物模型中产生有效的抗伤害感受作用。然而，1介导的抗伤害感受中涉及的生化事件目前还不清楚。本研究对Which 1发挥药理作用的机制进行了探讨。用1对小鼠进行急性预处理，对完全弗氏佐剂（CFA）诱导的痛觉过敏产生持久的镇痛作用。1亚慢性给药可抑制CFA引起的痛敏和足肿胀;另一组实验表明，1抑制角叉菜胶诱导的机械性痛觉过敏，但不抑制前列腺素E-2（PGE（2））诱导的机械性痛觉过敏，这表明它作用于PGE 2的上游，用1处理能够防止由局部炎症刺激引起的足底组织中性粒细胞炎症。此外，1对痛觉过敏细胞因子（TNF-α和IL-1 β）的释放和PGE（一种直接作用的痛觉过敏介质）的产生具有抑制作用（2）。本研究结果提示，1的抗伤害作用与抑制中性粒细胞迁移、细胞因子释放、神经元凋亡有关。和PGE 2的产生，并支持进一步研究1的治疗潜力，以控制炎性疼痛
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 atinociceptive 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 mechanial hyperalgesia, but not, mechanical hyperalgesia induced by prostaglandin E-2 (PGE(2)), suggesting that it acts upstream of PGE2, Treatment with 1 Was able to prevent the plantar tissue neutrophil"infltix induced by local inflammatory stimuli. In addition, 1 exhibited inhibitory effects on the release of hyperalgesic cytokines (TNF-alpha and IL-1 beta) 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 PGE2 production and are supportive of the further Investigation of the therapeutic potential of 1, to control inflammatory Pain