The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling

Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:2-12. doi: 10.1016/j.prostaglandins.2014.09.001. Epub 2014 Sep 18.


Lipid derived mediators contribute to inflammation and the sensing of pain. The contributions of omega-6 derived prostanoids in enhancing inflammation and pain sensation are well known. Less well explored are the opposing anti-inflammatory and analgesic effects of the omega-6 derived epoxyeicosatrienoic acids. Far less has been described about the epoxidized metabolites derived from omega-3 long chain fatty acids. The epoxide metabolites are turned over rapidly with enzymatic hydrolysis by the soluble epoxide hydrolase being the major elimination pathway. Despite this, the overall understanding of the role of lipid mediators in the pathology of chronic pain is growing. Here, we review the role of long chain fatty acids and their metabolites in alleviating both acute and chronic pain conditions. We focus specifically on the epoxidized metabolites of omega-6 and omega-3 long chain fatty acids as well as a novel strategy to modulate their activity in vivo.

Keywords: EpDPEs); Epoxy fatty acids (EpFAs); Epoxydocosapentanoic acids (EDP; Epoxyeicosatrienoic acids (EETs); Omega-3 fatty acids; Pain; Soluble epoxide hydrolase (sEH).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents / metabolism
  • Epoxide Hydrolases / metabolism
  • Epoxy Compounds / metabolism*
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-6 / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Nociception / physiology*
  • Nociceptive Pain / metabolism*
  • Signal Transduction


  • Anti-Inflammatory Agents
  • Epoxy Compounds
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Epoxide Hydrolases