Comparative efficacy of 3 soluble epoxide hydrolase inhibitors in rat neuropathic and inflammatory pain models

Karen Wagner, Bora Inceoglu, Hua Dong, Jun Yang, Sung Hee Hwang, Paul Jones, Christophe Morisseau, Bruce D. Hammock

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)93-101
Number of pages9
JournalEuropean Journal of Pharmacology
Volume700
Issue number1-3
DOIs
StatePublished - Jan 30 2013

Keywords

  • Diabetic neuropathic pain
  • Epoxygenated fatty acid
  • Inflammatory pain
  • Nociception
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Pharmacology

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    Wagner, K., Inceoglu, B., Dong, H., Yang, J., Hwang, S. H., Jones, P., Morisseau, C., & Hammock, B. D. (2013). Comparative efficacy of 3 soluble epoxide hydrolase inhibitors in rat neuropathic and inflammatory pain models. European Journal of Pharmacology, 700(1-3), 93-101. https://doi.org/10.1016/j.ejphar.2012.12.015