Palmitoylethanolamide in the human body
Palmitoylethanolamide can be produced in almost every cell by on-demand synthesis when needed, and in the amounts that are needed. Its production is naturally increased in situations where cells or tissues are damaged, or are threatened to become damaged. The metabolism of palmitoylethanolamide in cells is not complex. Cells can synthesize palmitoylethanolamide from fat-like substances already present in the cell membrane via the precursor n-acylphosphatidylethanolamine (NAPE). Degradation is simple as well: any cell that can synthesize palmitoylethanolamide has access to the fatty acid amide hydrolase (FAAH) enzyme. This enzyme can break palmitoylethanolamide down to its building blocks which can then be reintegrated in the cell membrane.
Palmitoylethanolamide restores unbalanced regulatory biological processes that may be disturbed, acutely or chronically, by a host of endogenous and exogenous mechanisms. This is achieved via impact on a particular nuclear receptor, the PPAR receptor. This nuclear receptor restores biochemical balance in cells and thereby preventing an excess of inflammatory factors and pain-promoting substances. Activation of this nuclear receptor plays an important role in analgesia.
Additional specific cellular targets of palmitoylethanolamide are mast cells and glial cells. Excessive activation of these cells are important factors in chronic pain. In fact, it has been known for several years that these satellite, non-neuronal cells may maintain chronic pain. Palmitoylethanolamide inhibits any excessive activity of these inflammatory cells. It restores their normal activity, thereby considerably decreasing the reactivity of chronic pain systems throughout the body. In addition to PPAR receptor activation and the calming effect on particularly mast cells and glial cells, many other mechanisms of action have been identified.