Dietary alteration of n-6 and n-3 fatty acids for chronic low back pain

ABSTRACT The NIH has declared that developing new non-addictive treatments for chronic pain is one of its top priorities. Certain polyunsaturated fatty acids are precursors to oxylipins that regulate pain pathways. Oxylipins derived from omega-6 (n-6) linoleic acid tend to have pro-nociceptive properties, while oxylipins derived from omega-3

eicosapentaenoic acid (n-3 EPA) and docosahexaenoic acid (DHA) tend to have anti-nociceptive properties. Because humans cannot synthesize n-3 and n-6 fatty acids de novo, the levels of these fatty acids—and their oxylipin derivatives—can be altered by diet. We have published results of two randomized

controlled trials testing targeted dietary modification of n-3 and n-6 fatty acids (H3L6 diet) among adults with chronic headache (n=67) and migraine (n=182) reporting reductions in headache of 25-40% and reduction in NSAID use. The H3L6 diet altered the concentration of circulating n-6 and n-3 fatty acids and their oxylipin

derivatives, and these changes predicted improvement in headache. These results suggest that the H3L6 diet is a promising adjunct treatment for reducing headache and a useful model for investigating mechanisms of pain reduction. Preclinical studies suggest that oxylipin modification could be efficacious in other chronic pain

conditions characterized by neuronal sensitization and inflammation, but this has not been demonstrated in humans. We have pilot data (n=40) supporting feasibility and reduced pain intensity in adults with chronic lumbosacral radiculopathy randomized to the H3L6 vs control diet. We propose to conduct a 16-week

randomized controlled trial testing the efficacy and biochemical mechanisms of the H3L6 diet among adults receiving usual care for chronic axial low back pain. We hypothesize that increasing dietary n-3 EPA+DHA while lowering n-6 linoleic acid will alter nociceptive oxylipins in a manner that decreases the intensity of back

pain as well as pain medication use. The goal of this R34 planning grant is to develop all the necessary documents and procedures to conduct that trial. In Aim 1, we will update the H3L6 and control interventions to current nutrient values since the food supply has changed since they were developed. In Aim 2, we will

complete all the planning activities (e.g., preparation of the manual of operating procedures, development of informed consent forms, and develop safety and data management plan) that are critical prior to implementing a clinical trial. Completion of this aim will take care of all requirements in the NIAMS Clinical Trial Planning

Milestone Checklist and will facilitate the launching of a trial that is hypothesis-driven and milestone- defined. The proposed project is part of a series of studies designed to translate the preclinical and clinical research on oxylipin-pain pathways into accessible, effective, non-addictive treatments for chronic pain. Based

on our previous work, this approach of using dietary modifications to alter biochemical regulators of chronic pain is a low-risk, high-reward endeavor potentially leading to new treatment options and biomarkers of treatment response.