Comparative efficacy of 3 soluble epoxide hydrolase inhibitors in rat neuropathic and inflammatory pain models.
Comparative efficacy of 3 soluble epoxide hydrolase inhibitors in rat neuropathic and inflammatory pain models.
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DOI：
10.1016/j.ejphar.2012.12.015
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发表时间：
2013-01-30
影响因子：
5
通讯作者：
Hammock, Bruce D.
中科院分区：
文献类型：
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作者：
Wagner, Karen;Inceoglu, Bora;Dong, Hua;Yang, Jun;Hwang, Sung Hee;Jones, Paul;Morisseau, Christophe;Hammock, Bruce D.
关键词：
环氧脂肪酸是重要的细胞信号分子，具有抗伤害等多种生物学效应。这些信号分子的主要降解途径是通过可溶性环氧化物水解酶（sEH）。sEH的抑制剂延长脂肪酸环氧化物的抗伤害感受作用。在这项研究中，两种不同病因的疼痛模型，链脲佐菌素诱导的I型糖尿病神经病理性疼痛和脂多糖诱导的炎性疼痛，用于测试sEH抑制剂。使用具有相同中心药效团但不同取代基部分的三种sEH抑制剂的剂量范围来研究这两种疼痛模型中的最大抗异常性疼痛作用。在这些模型中抑制sEH酶成功地阻断了两种模型中的疼痛相关行为。sEH抑制剂在减轻糖尿病性神经性疼痛和脂多糖诱导的炎性疼痛方面比塞来昔布更有效。由于其阻断糖尿病性神经病理性疼痛的能力，sEH抑制是治疗慢性疼痛病症的有希望的新方法。
Epoxy-fatty acids have been recognized as important cell signaling molecules with multiple biological effects including anti-nociception. The main degradation pathway of these signaling molecules is via the soluble epoxide hydrolase (sEH) enzyme. Inhibitors of sEH extend the anti-nociceptive effects of fatty acid epoxides. In this study two models of pain with different etiology, streptozocin induced type I diabetic neuropathic pain and lipopolysaccharide induced inflammatory pain were employed to test sEH inhibitors. A dose range of three sEH inhibitors with the same central pharmacophore but varying substituent moieties was used to investigate maximal anti-allodynic effects in these two models of pain. Inhibiting the sEH enzyme in these models successfully blocked pain related behavior in both models. The sEH inhibitors were more potent and more efficacious than celecoxib in reducing both diabetic neuropathic pain and lipopolysaccharide induced inflammatory pain. Because of their ability to block diabetic neuropathic pain sEH inhibition is a promising new approach to treat chronic pain conditions.
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影响因子：
5
作者：
Fukuda，Kyoichi;Tesch，Greg H.;Nikolic-Paterson，David J.
通讯作者：
Nikolic-Paterson，David J.
DOI：
10.1073/pnas.1011278107
发表时间：
2010-09-28
影响因子：
11.1
作者：
Liu, Jun-Yan;Li, Ning;Hammock, Bruce D.
通讯作者：
Hammock, Bruce D.
影响因子：
7.3
作者：
Hwang, Sung Hee;Tsai, Hsing-Ju;Hammock, Bruce D.
通讯作者：
Hammock, Bruce D.
影响因子：
2.7
作者：
Morisseau, Christophe;Newman, John W.;Hammock, Bruce D.
通讯作者：
Hammock, Bruce D.
DOI：
10.1038/nrd2875
发表时间：
2009-10
期刊：
Nature reviews. Drug discovery
影响因子：
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作者：
通讯作者：
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