PEA and the family of fatty acid ethanolamines (FAE) are involved in cell protection. They are part of the human’s innate system of endogenous protection from cellular damage. These lipid mediators are activated by tissue damage, inflammatory processes and nociceptive fibers.

The family of FAEs include:

Anadamide
N-oleoylethanolamine
Palmitoylethanolamide
N-stearoylethanolamine

HOW PEA REDUCES NEUROINFLAMMATION

Neuroinflammation is characterized by an increase in the amount and activity of the inflammasomes. These complexes mediate neuroinflammation along with cytokines and chemokines. Inflammasomes activate caspase-1 and this leads to production of Il-1B, IL-18, IL-33; these are pro-inflammatory molecules.

These cytokines play a large role in starting the terrible cascade of neuroinflammation and neurodegeneration.

Cytokines are large proteins that are secreted from immune cells. These may be pro or anti inflammatory. They work to achieve homeostasis for the cell in terms of inflammation. The pro-inflammatory interleukins are IL-1B, IL-6, IL-18, TNF-alpha. The anti-inflammatory ones include IL-4 and IL-10.

Chemokines have a basic role to cause cell migration. These can be considered chemotactic cytokines.

Once induced and the cellular environment becomes highly inflammatory, an internal protection system should turn on and begin resolving the inflammation.

This neuroinflammation resolution process involves lipid mediators that are able to switch off the inflammation.

These lipid mediators can convert a chronically inflamed situation to a normal and balanced one.

Some lipid mediators known in the inflammatory cascade are prostaglandins, leukotrienes and eicosanoids.

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Once the cell is too inflamed, the resolvins, protectins and maresins should come into play. However, most people exist in a state of chronic inflammation and oxidative stress and this system is overwhelmed completely.

HOW PEA REDUCES OXIDATIVE STRESS

PEA is a ligand for peroxisome proliferator actuator receptor alpha (PPAR-alpha). PPARs are a group of receptors that act as transcription factors and regulate the expression of certain genes.

PEA can also bind to GPR55 a ubiquitous receptor on neural cell membranes. THis receptor modulate neutrophil migration and may prevent oxidative damage.

PEA is made by mast cells and glial cells. Mast cells are immune cells and glial cells are neural support cells and function as neural immune cells as well. When mast and glial cells are overactivated with chronic inflammation, they cause damage.

PEA is part of the normal negative feedback loop designed to downregulate the activity of these cells. For example, Mast cell degranulation at peripheral nerves is known to cause chronic neuropathic pain; PEA can mitigate that result and resolve chronic neuropathic pain.

PEA is neuroprotective and antinociceptive. PEA can decrease NO production, decrease neutrophil influx and decrease the expression of proinflammatory proteins. It also protects endothelial function from oxidative and inflammatory injuries.

PEA AND BRAIN HEALTH

PEA administration has been found to improve the function of brains after TBI; it enhances neurological, biochemical and emotional outcomes. It does so by reducing the second injury aspect of TBI by preventing the brain’s infiltration by and degranulation of mast cells.

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The exogenous addition of PEA can accelerate the resolution of inflammation. PEA acts to restore cellular and mitochondrial balance.

PEA offers a safe and natural method to manage neuropathic pain; it is tolerated very well and there are no known side effects. This is a naturally occurring lipid mediator that is an inflammation resolver.

PEA has shown pro-neurogenic effects in the hippocampus and has also protected against alterations by inflammation of the dopamine active transporter in the substantia nigra. It is being studied as a therapy to prevent dopamine neuronal cell destruction in Parkinson’s.

There are many clinical studies showing the effectiveness of PEA in reducing pain from nerves and also in reducing the need for other medications like NSAIDs. This protects against the side effects of the NSAIDs.

PEA acts mostly on the support cells, or non-neuronal cells, of the CNS and is an important natural method to prevent neuroinflammation, neurodegeneration and pain.