Dietary linoleic acid-induced alterations in pro- and anti-nociceptive lipid autacoids: Implications for idiopathic pain syndromes?

Mol Pain. 2016 Mar 10;12:1744806916636386. doi: 10.1177/1744806916636386. Print 2016.


Background: Chronic idiopathic pain syndromes are major causes of personal suffering, disability, and societal expense. Dietary n-6 linoleic acid has increased markedly in modern industrialized populations over the past century. These high amounts of linoleic acid could hypothetically predispose to physical pain by increasing the production of pro-nociceptive linoleic acid-derived lipid autacoids and by interfering with the production of anti-nociceptive lipid autacoids derived from n-3 fatty acids. Here, we used a rat model to determine the effect of increasing dietary linoleic acid as a controlled variable for 15 weeks on nociceptive lipid autacoids and their precursor n-6 and n-3 fatty acids in tissues associated with idiopathic pain syndromes.

Results: Increasing dietary linoleic acid markedly increased the abundance of linoleic acid and its pro-nociceptive derivatives and reduced the abundance of n-3 eicosapentaenoic acid and docosahexaenoic acid and their anti-nociceptive monoepoxide derivatives. Diet-induced changes occurred in a tissue-specific manner, with marked alterations of nociceptive lipid autacoids in both peripheral and central tissues, and the most pronounced changes in their fatty acid precursors in peripheral tissues.

Conclusions: The present findings provide biochemical support for the hypothesis that the high linoleic acid content of modern industrialized diets may create a biochemical susceptibility to develop chronic pain. Dietary linoleic acid lowering should be further investigated as part of an integrative strategy for the prevention and management of idiopathic pain syndromes.

Keywords: Oxylipin; idiopathic; linoleic acid; omega-3; omega-6; pain.

Publication types

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

MeSH terms

  • Animals
  • Autacoids / pharmacology*
  • Dietary Fats / pharmacology*
  • Fatty Acids, Omega-3 / pharmacology
  • Linoleic Acid / pharmacology*
  • Male
  • Nociception / drug effects*
  • Organ Specificity / drug effects
  • Oxylipins / pharmacology
  • Pain / pathology*
  • Rats, Inbred F344
  • Syndrome


  • Autacoids
  • Dietary Fats
  • Fatty Acids, Omega-3
  • Oxylipins
  • Linoleic Acid