Epoxygenated fatty acids and soluble epoxide hydrolase inhibition: Novel mediators of pain reduction

Karen Wagner, Bora Inceoglu, Sarjeet S. Gill, Bruce D. Hammock

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The soluble epoxide hydrolase (sEH) enzyme was discovered while investigating the metabolism of xenobiotic compounds in the Casida laboratory. However, an endogenous role of sEH is to regulate the levels of a group of potent bioactive lipids, epoxygenated fatty acids (EFAs), that have pleiotropic biological activities. The EFAs, in particular the arachidonic acid derived epoxy eicosatrienoic acids (EETs), are established autocrine and paracrine messengers. The most recently discovered outcome of inhibition of sEH and increased EFAs is their effects on the sensory system and in particular their ability to reduce pain. The inhibitors of sEH block both inflammatory and neuropathic pain. Elevation of EFAs, in both the central and peripheral nervous systems, blocks pain. Several laboratories have now published a number of potential mechanisms of action for the pain-reducing effects of EFAs. This paper provides a brief history of the discovery of the sEH enzyme and argues that inhibitors of sEH through several independent mechanisms display pain-reducing effects.

Original languageEnglish (US)
Pages (from-to)2816-2824
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Volume59
Issue number7
DOIs
StatePublished - Apr 13 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

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