Dietary linoleic acid-induced alterations in pro- and anti-nociceptive lipid autacoids: Implications for idiopathic pain syndromes? - PubMed (original) (raw)
. 2016 Mar 10:12:1744806916636386.
doi: 10.1177/1744806916636386. Print 2016.
Amit Ringel 2, Sharon F Majchrzak-Hong 2, Jun Yang 3, Helene Blanchard 4, Daisy Zamora 5, James D Loewke 2, Stanley I Rapoport 6, Joseph R Hibbeln 2, John M Davis 7, Bruce D Hammock 3, Ameer Y Taha 8
Affiliations
- PMID: 27030719
- PMCID: PMC4955998
- DOI: 10.1177/1744806916636386
Dietary linoleic acid-induced alterations in pro- and anti-nociceptive lipid autacoids: Implications for idiopathic pain syndromes?
Christopher E Ramsden et al. Mol Pain. 2016.
Abstract
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.
© The Author(s) 2016.
Figures
Figure 1.
Proposed mechanisms linking high intake of linoleic acid to chronic pain. (a) Dietary LA can be endogenously converted to pro-nociceptive mediators (e.g. 9-HODE). A small fraction of dietary LA is converted to n-6 AA, the precursor to pro- and anti-nociceptive mediators. High intakes of dietary LA competitively inhibit hepatic conversion of n-3 ALA into EPA and DHA. (b) In circulation, LA and HODE are predominantly esterified in cholesteryl esters, triacylglycerol, and phospholipid components of lipoproteins. LA and HODE in circulating LDL are delivered to peripheral tissues via LDL receptors and scavenger receptors. (c) High intakes of LA produce tissue-specific increases in LA and AA and reduction in EPA and DHA content of cellular membranes. (d) High intake of dietary LA increases the production of pro-nociceptive mediators (e.g. 9-HODE and PGE2) and reduces the production of anti-nociceptive lipid autacoids (e.g. EpDPEs and EpETEs). (e) These alterations in nociceptive lipid mediators modulate receptors (e.g. TRPV1, E-prostanoid) creating a biochemical susceptibility to develop chronic pain. LA: linoleic acid; ALA: α-linolenic acid; AA: arachidonic acid; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; CE: cholesteryl ester; PL: phospholipid; HODE: hydroxyoctadecadienoic acid; EpDPE: Epoxy-docosapentaenoic acid GPCR, G-protein coupled receptor; TRPV1: transient receptor potential vanilloid, type 1.
Figure 2.
Dietary LA-induced changes in the fatty acid content of peripheral tissues associated with idiopathic pain syndromes. Note that the Y-axis scales differ in these graphs. X-axis % values refer to percentage of food energy. Box plots include medians and interquartile ranges with end whiskers set to minimum and maximum values. Number of samples for each tissue (perineum n = 21, epididymis n = 21, skeletal muscle n = 24, bladder n = 21, duodenum n = 21, and esophagus n = 20). LA: linoleic acid; AA: arachidonic acid; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid.
Figure 3.
Dietary LA-induced changes in fatty acids in central nervous system tissues. Note that the Y-axis scales differ in these graphs. X-axis % values refer to percentage of food energy. Box plots include medians and interquartile ranges with end whiskers set to minimum and maximum values. Number of samples for each tissue (cervical cord n = 23, brainstem n = 24, and cerebellum n = 24). LA: linoleic acid; AA: arachidonic acid; DTA: docosatetraenoic acid; DHA: docosahexaenoic acid.
Figure 4.
Diet-induced changes in total (sum of free and esterified) n-3 and n-6 derived oxylipins in tissues associated with idiopathic pain syndromes. Note that the Y-axis scales differ in these graphs. Note that the Y-axis scales differ in these graphs. Box plots include medians and interquartile ranges with end whiskers set to 1.5 times interquartile values. Number of samples for each tissue (bladder n = 20, perineum n = 18, and cervical cord n = 21). HODE: hydroxyoctadecadienoic acid; EpOME: epoxyoctadecamonoenoic acid; EpETrE: epoxyeicosateteaenoic acid; EpDPE: epoxydocosapentaenoic acid.
Figure 5.
Diet-induced changes in free (unesterified) n-3 and n-6 derived oxylipins in tissues associated with idiopathic pain syndromes. Note that the Y-axis scales differ in these graphs. Box plots include medians and interquartile ranges with end whiskers set to 1.5 times interquartile values. Number of samples for each tissue (bladder n = 20, perineum n = 18, and cervical cord n = 21). HODE: hydroxyoctadecadienoic acid; EpOME: epoxyoctadecamonoenoic acid; PG: prostaglandin; EpETE: epoxyeicosateteaenoic acid; EpDPE: epoxydocosapentaenoic acid.
Figure 6.
Linoleic acid content of study diets compared to current and historical intakes. Distribution of LA intakes in U.S. adults. Dose of LA needed to prevent deficiency symptoms. Calculated from USDA economic disappearance data. Modeled from hunter-gatherer diets.
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