# Effects of a High Omega-6 Diet on Orofacial Allodynia

> **NIH NIH F30** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $54,774

## Abstract

ABSTRACT
Chronic orofacial pain is estimated to be experienced by up to 25% of the adult population, which greatly
decreases quality of life. A common complaint of orofacial pain is from mechanical stimuli. Current treatments
for various orofacial pain conditions are limited. Physicians recommend dietary interventions for management of
disorders such as cardiovascular disease and diabetes, but less is known about how diet may alleviate pain. It
is possible that diet may also contribute to chronic orofacial pain conditions, as omega-6 polyunsaturated fatty
acids (PUFAs) such as linoleic acid (LA) and arachidonic acid (AA), are essential PUFAs that are regulated by
dietary intake and known to be pronociceptive. Our data demonstrate that mice fed an 8-week high omega-6
diet (H6D) exhibit increased plasma membrane levels of LA and AA in dorsal root ganglia (DRG) and increased
hindpaw sensitivity to mechanical stimuli. LA, AA, and their metabolites could be regulating nociception through
activation of channels in primary afferent nociceptors. More specifically, LA and AA are cleaved from membranes
by phospholipase A2 (PLA2) isozymes where they can be oxidized into biologically active metabolites, which
can activate targets like transient receptor potential channels expressed on primary afferent nociceptors.
Therefore, the release of omega-6 PUFAs from cellular membranes may play a key role in regulating nociceptor
activities and pain. However, it is unknown whether a H6D is a pain risk factor in orofacial tissues innerved by
trigeminal ganglia (TG) afferent neurons. Given the distinct molecular expression differences between TG and
DRG neurons, studies on the role of H6D as a risk factor for orofacial pain must be conducted in the TG system.
Our preliminary data demonstrates that mice fed a H6D for 8-weeks exhibit significantly increased orofacial
responsiveness to mechanical stimuli filaments. There is a large gap in knowledge as to the mechanisms by
which dietary intake of omega-6 lipids serves as a risk factor for orofacial pain. Based on recent studies and
our preliminary data, we propose to test the central hypothesis that increased dietary omega-6 PUFAs
sensitize trigeminal sensory neurons and increase nociceptive behaviors in preclinical models of
inflammatory and neuropathic orofacial pain via neuronal phospholipase A2. To investigate the role of diet
on orofacial pain, we will 1) examine the role of H6D in sensitization of sensory neurons, 2) determine if H6D is
a pronociceptive risk factor in models of orofacial pain conditions, and 3) identify PLA2 isozymes mediated H6D-
induced effects on mechanical nociceptive behaviors. The scientific significance is based on an innovative
hypothesis and may lead to novel therapeutic interventions for orofacial pain conditions. Although dietary
recommendations are made for many diseases, they represent a new approach for managing orofacial pain.
These dietary interventions may offer considerable clinical...

## Key facts

- **NIH application ID:** 10843131
- **Project number:** 5F30DE031177-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Meilinn Tram
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $54,774
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843131

## Citation

> US National Institutes of Health, RePORTER application 10843131, Effects of a High Omega-6 Diet on Orofacial Allodynia (5F30DE031177-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10843131. Licensed CC0.

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