Nat Metabol: Another kind of pain is to eat too much essential fatty acids and damage your peripheral nerves.

The cell membrane level of essential fatty acids is regulated by dietary intake, and its demand accounts for about 1% of total calories
.

However, the average daily Western diet contains 10-20 times the level of omega-6

This typical Western diet is rich in omega-6 polyunsaturated fatty acids (PUFA), which accumulate in membrane phospholipids and are oxidized into nociceptive oxidized lipid compounds
.

Excessive intake of omega-6 polyunsaturated fatty acids (ω-6 PUFAs) including linoleic acid (LA) and arachidonic acid (AA) is a risk factor for chronic pain
.

On June 17, 2021, the Kenneth M.
Hargreaves research team at the University of Texas Health Sciences Center in San Antonio revealed that excessive intake of omega-6 polyunsaturated fatty acids caused peripheral neurofibrosis, nociceptive hypersensitivity, and aggravated pain
.

Mice with high concentrations of omega-6 PUFAs have paresthesias, while low concentrations do not

Mice with high concentrations of omega-6 PUFAs will have paresthesias, while low concentrations will not.
Mice with high concentrations of omega-6 PUFAs will have paresthesias, while low concentrations will not

After 4 weeks of continuous feeding of high-concentration omega-6 PUFAs (hereinafter referred to as H6D mice), the mice showed obvious mechanical, thermal, and cold allergies, reaching a peak at the 8th week
.

Mice raised with low concentrations of omega-6 PUFAs do not have the above obstacles

Decreased density of intraepidermal nerve fibers in the skin of the hind paw of H6D mice

The density of intraepidermal nerve fibers in the skin of the hind paws of H6D mice decreased.
The density of intraepidermal nerve fibers in the skin of the hind paws of H6D mice decreased.

The fibers that transmit painful impulses are mainly A fibers and C fibers
.

The activity of these fibers was enhanced by mechanical stimulation after feeding with high concentrations of omega-6 PUFAs

The levels of linoleic acid (LA) and arachidonic acid (AA) only increased in the dorsal root ganglia of H6D mice
.

The expression and activity level of phospholipase A2 (PLA2) isoenzymes regulate the release of LA and AA

Previous single-cell sequencing studies have shown that PLA2g7 is the most important isoenzyme of PLA2, accounting for 70-90% of PLA2 transcription in all sensory neurons
.

PLA2g7 selective inhibitor can reduce the activity of PLA2 by 80% on the overall level

Plantar injection of this inhibitor can significantly improve the mechanical hypersensitivity of H6D mice
.

Then they used viral vector tools to silence PLA2g7 in the dorsal root ganglion, which can also exert a similar improvement function

What's interesting is that ω-3 PUFAs have anti-inflammatory and anti-nociceptive effects, and can directly "combat" the pro-inflammatory and nociceptive effects caused by metabolites of ω-6 PUFAs
.

If these two diets are balanced, can it block peripheral neuropathy in H6D mice

After 8 weeks of continuous feeding of high-concentration omega-6 PUFAs, the researchers replaced them with high-concentration omega-3PUFAs.

As a result, the hyperesthesia symptoms of these mice fed with omega-3PUFAs were significantly improved, and the intradermal nerve fiber density returned to normal levels.

Does omega-6 PUFAs, such as diet-induced injury hyperesthesia, affect pain perception
? The researchers used Complete Freund's Adjuvant (CFA) to induce chronic pain models.
After these painful mice were fed with high concentrations of omega-6 PUFAs, the time of allodynia symptoms was about 3 times longer
.

Diabetic mice developed more severe mechanical allodynia after being fed with high concentrations of omega-6 PUFAs
.
But feeding on omega-3PUFAs does not cause such pain abnormalities
.
This indicates that H6D may be a risk factor for aggravating inflammation or neurological damage-related nociception, but it can be blocked by omega-3 PUFAs
.

In general, a typical Western diet of just 8 weeks promotes the enrichment of DRG and omega-6 PUFAs in the skin, leading to increased PLA2-mediated lipid release, and leading to peripheral nerve damage and noxious hypersensitivity.
Fortunately, this damage is reversible
.

Original source:

Original source:

Boyd, JT, LoCoco, PM, Furr, AR et al.
Elevated dietary ω-6 polyunsaturated fatty acids induce reversible peripheral nerve dysfunction that exacerbates comorbid pain conditions.
Nat Metab 3, 762–773 (2021).
https://doi.
org/10.
1038/s42255-021-00410-x.

Elevated dietary ω-6 polyunsaturated fatty acids induce reversible peripheral nerve dysfunction that exacerbates comorbid pain conditions.
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