Already many years ago, in the last century nice models were introduced to demonstrate the biological effects of PEA. One such models was the injection of an irritative natural compound, substance P in the ear of mice. Substance P is an endogenous molecule that activates inflammation.
If mice are pretreated with 10 mg/kg pure palmitoylethanolamide per os, the inflammation of the ear is inhibited. By studying the behavior of the mast cells in the ear, researchers could see that PEA inhibited the inflammation behavior of the mast cells.
The authors worked at that time with 99% pure PEA under the code name LG 2110/1 and stated:
Recently, N-(2-hydroxyethyl)hexadecanamide (LG 2110/1) has been reported to down-modulate mast cell activation in vitro ….
Here, we have characterized and functionally correlated the anti-inflammatory actions of LG 2110/1 with its ability to control mast cell activation, when given orally in a battery of rodent models of inflammation. LG 2110/1 diminished, in a dose-dependent and correlated manner, the number of degranulated mast cells and plasma extravasation induced by substance P injection in the mouse ear pinna.
Mazzari S, Canella R, Petrelli L, Marcolongo G, Leon A. N-(2-hydroxyethyl)hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation. Eur J Pharmacol. 1996 Apr 11;300(3):227-36.