Palmitoylethanolamide PEA, PEA

The existence of acylethanolamides (AE) in the brain of mammals has been known for decades. Among the side effects, palmitoylethanolamide (PEA) is found in large quantities in the central nervous system (CNS) and is noticeably produced by neurons and glial cells.

The antihyperalgesic and neuroprotective properties of PEA are mainly associated with the reduction of neuronal excitation and the control of inflammation. A growing body of evidence indicates that PEA can be neuroprotective in neurodegenerative diseases of the central nervous system.

Advances in understanding the physiology and pharmacology of PEA have strengthened its interest as a useful biological tool for the treatment of diseases. Several rapid nongenomic and delayed genomic mechanisms of action have been identified for PEA as a peroxisome proliferator-activated receptor (PPAR)-α.

First, early molecular control through the opening of Ca(+2)-activated intermediate and/or large K(+) conductance channels leads to rapid hyperpolarization of neurons. This is enhanced by an increase in internal Cl(-) currents due to modulation of the gamma-aminobutyric acid A receptor and desensitization of the transient potential receptor channel of the V1 type. In addition, the mechanism mediated by gene transcription supports long-term anti-inflammatory effects, reducing the expression of pro-inflammatory enzymes and increasing the synthesis of neurosteroids.

In general, the integration of these different modes of action allows PEA to carry out immediate and long-term effective control of neuronal signaling either on the inflammatory process or on neuronal excitability, supporting cellular homeostasis.