Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids

J Lipid Res. 2010 Dec;51(12):3481-90. doi: 10.1194/jlr.M006007. Epub 2010 Jul 27.


Beneficial physiological effects of long-chain n-3 polyunsaturated fatty acids are widely accepted but the mechanism(s) by which these fatty acids act remains unclear. Herein, we report the presence, distribution, and regulation of the levels of n-3 epoxy-fatty acids by soluble epoxide hydrolase (sEH) and a direct antinociceptive role of n-3 epoxy-fatty acids, specifically those originating from docosahexaenoic acid (DHA). The monoepoxides of the C18:1 to C22:6 fatty acids in both the n-6 and n-3 series were prepared and the individual regioisomers purified. The kinetic constants of the hydrolysis of the pure regioisomers by sEH were measured. Surprisingly, the best substrates are the mid-chain DHA epoxides. We also demonstrate that the DHA epoxides are present in considerable amounts in the rat central nervous system. Furthermore, using an animal model of pain associated with inflammation, we show that DHA epoxides, but neither the parent fatty acid nor the corresponding diols, selectively modulate nociceptive pathophysiology. Our findings support an important function of epoxy-fatty acids in the n-3 series in modulating nociceptive signaling. Consequently, the DHA and eicosapentaenoic acid epoxides may be responsible for some of the beneficial effects associated with dietary n-3 fatty acid intake.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Disease Models, Animal
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / pharmacology
  • Docosahexaenoic Acids / therapeutic use*
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / pharmacology
  • Eicosapentaenoic Acid / therapeutic use*
  • Epoxide Hydrolases / metabolism
  • Epoxy Compounds / administration & dosage
  • Epoxy Compounds / pharmacology
  • Epoxy Compounds / therapeutic use*
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Kinetics
  • Male
  • Pain / drug therapy
  • Pain / metabolism
  • Pain / pathology
  • Rats
  • Rats, Sprague-Dawley


  • Epoxy Compounds
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Epoxide Hydrolases