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Title: Epoxygenated fatty acids and soluble epoxide hydrolase inhibition: novel mediators of pain reduction.

Authors: Wagner, Karen; Inceoglu, Bora; Gill, Sarjeet S; Hammock, Bruce D

Published In J Agric Food Chem, (2011 Apr 13)

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.

PubMed ID: 20958046 Exiting the NIEHS site

MeSH Terms: Analgesia*; Anti-Inflammatory Agents; Epoxide Hydrolases/antagonists & inhibitors*; Epoxide Hydrolases/physiology*; Epoxy Compounds; Fatty Acids/physiology*; Inflammation; Nervous System/drug effects; Nociceptors; Pain*

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