title: Comparative efficacy of 3 soluble epoxide hydrolase inhibitors in rat neuropathic and inflammatory pain models.
abstract: 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.
authors.affiliation: Department of Entomology and UC Davis Comprehensive Cancer Center, University of California Davis, One Shields Ave, Davis, CA 95616, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Wagner
authors.forename: Bora
authors.initials: B
authors.lastname: Inceoglu
authors.forename: Hua
authors.initials: H
authors.lastname: Dong
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Paul
authors.initials: P
authors.lastname: Jones
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D007249:Inflammation / Q000150:complications; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D054883:Oxylipins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D054883:Oxylipins; D004851:Epoxide Hydrolases