Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 700, Issue 1-3, Pages 93-101Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2012.12.015
Keywords
Nociception; Soluble epoxide hydrolase; Inflammatory pain; Diabetic neuropathic pain; Epoxygenated fatty acid
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Funding
- National Institute of Environmental Health Sciences (NIEHS) [R01 ES002710]
- NIEHS Superfund Research Program [P42 ES004699]
- NIEHS [T32ES007059]
- NIH [5T32DC008072-05]
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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. (C) 2012 Elsevier B.V. All rights reserved.
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