# Potential mechanisms underlying a relationship between long-chain polyunsaturated fatty acids and overlapping pain conditions in adults

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $233,250

## Abstract

Chronic pain therapies typically target one of three pain pathways: nociception, inflammation or psychological
processes. The goal is almost always therapeutic, not preventive. We challenge that premise in light of new
evidence that chronic pain can be prevented by targeting all three pathways through diets with a favorable
balance of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs). The anti-inflammatory
effects of long-chain (LC) omega-3 (n-3) PUFAs on pain disorders such as arthritis are well recognized. A
more recent discovery is that LC n-3 eicosapentaenoic acid and n-3 docosahexaenoic acid metabolites lower
concentrations of pronociceptive derivatives, and increase concentrations of antinociceptive and analgesic
derivatives. By contrast, omega-6 (n-6) PUFA metabolites have mostly inflammatory and pronociceptive
effects. Furthermore, LC n-3 derivatives have anxiolytic effects, alleviating depressive symptoms and anxiety
that are often comorbid with chronic pain. The extent to which n-6 and n-3 PUFAs are synthesized into
bioactive LC PUFAs by fatty acid desaturase (FADS) enzymes, encoded by the FADS gene cluster, differs
according to genetic variability in key enzymes in PUFA metabolism: delta-5 desaturase (FADS1) and delta-6
desaturase (FADS2). Hence gene-PUFA interactions influence the biosynthesis of PUFA derivatives that have
putative and therapeutic effects on chronic pain. We plan to study associations between PUFAs and chronic
overlapping pain conditions (COPCs) cross-sectionally using existing data and stored erythrocytes from 655
genotyped adult participants (69% women) in our community-based study named “Orofacial Pain: Prospective
Evaluation and Risk Assessment” (OPPERA-II). OPPERA-II assessed overlap of temporomandibular disorder,
migraine or tension-type headache, fibromyalgia, low back pain, and irritable bowel syndrome. Aim 1 will
evaluate associations between pain conditions and erythrocyte concentrations of PUFAs and their metabolites.
PUFAs will be quantified using liquid chromatography tandem mass spectrometry. We hypothesize that high
concentrations of the n-6 series, and low concentrations the n-3 series are positively associated with
occurrence of each pain condition and the total number of COPCs. Aim 2 will evaluate associations between
intermediate phenotypes (nociception, anxiety and depression) and PUFA concentrations. Anxiety and
depressive symptoms were measured by psychometrically validated questionnaires. Quantitative sensory
testing determined sensitivity to three modalities of nociception: blunt pressure pain, mechanical pain, and
thermal heat pain. Aim 3 will assess whether FADS genetic variants modify associations of PUFAs and their
metabolites with COPCs. This is a high risk project because community-based studies of pain have never
assessed PUFAs’ potential for preventing COPCs. Such a study is a necessary pre-requisite for a future
clinical trial. The project has potentially high-reward ...

## Key facts

- **NIH application ID:** 10213009
- **Project number:** 5R21DE029746-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Anne E. Sanders
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $233,250
- **Award type:** 5
- **Project period:** 2020-07-08 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213009

## Citation

> US National Institutes of Health, RePORTER application 10213009, Potential mechanisms underlying a relationship between long-chain polyunsaturated fatty acids and overlapping pain conditions in adults (5R21DE029746-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213009. Licensed CC0.

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