Journal
JOURNAL OF PAIN
Volume 16, Issue 8, Pages 707-716Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.jpain.2015.04.007
Keywords
Endocannabinoids; psychological distress; headache; 2-docosahexaenoylglycerol; docosahexaenoylethanolamine; 2-arachidonoylglycerol
Categories
Funding
- Mayday Fund
- UNC (NCCAM, NIH) [T32-AT003378]
- North Carolina Clinical and Translational Sciences Institute (NCRR, NIH) [UL1RR025747]
- UNC Nutrition Obesity Research Center, CHAI Core (NIDDK, NIH) [DK056350]
- National Institute on Drug Abuse [DA07215, DA09158]
- National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001111] Funding Source: NIH RePORTER
- National Center for Complementary & Integrative Health [T32AT003378] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025747] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK056350] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [ZIAAA000115, ZIAAA000262, ZIAAA000235] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P01DA009158, R01DA007215] Funding Source: NIH RePORTER
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Omega-3 and omega-6 fatty acids are biosynthetic precursors of endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation-increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-16 intervention) reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (N = 55) to investigate 1) whether the H3-L6 intervention altered omega-3- and omega-6-derived endocannabinoids in plasma and 2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, P < .001) and docosahexaenoylethanolamine (+99%, P < .001) and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, P = .001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties. Trial registration: ClinicalTrials.gov (NCT01157208) Perspective: This article demonstrates that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids and that these changes are related to reductions in headache pain and psychological distress. These findings suggest that dietary interventions could provide an effective, complementary approach for managing chronic pain and related conditions. Published by Elsevier Inc. on behalf of the American Pain Society
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