Palmitoylethanolamide (PEA) is a powerful natural active ingredient discovered in 1957, which boasts of the fact that our lamented Professor "Nobel Prize" Rita Levi Montalcini in 1993 he identified the complex mechanisms of action, highlighting its activity orally in the reduction of tissue inflammation (inflammation) and mast cell degranulation in vivo, decreasing the hyperalgesia that accompanies the compression of the peripheral nerve. The same Prof. Montalcini, already made it clear that Palmitoylethanolamide could have interesting properties also aimed at the treatment of chronic pain, with potential other indications, highlighted by a vast scientific literature available.
Palmitoylethanolamide (PEA), the amide of palmitic acid with ethanolamine, is an active element present in many foods commonly introduced by our diet, such as eggs, peanuts, peas, tomatoes, soy, etc, and is itself produced also from many cells of our organism. It is present in high concentrations in brain tissues and is synthesized starting from phospholipid precursors of cell plasma membranes, being an endogenous factor, produced by our body to counteract inflammation and restore the physiological functionality of damaged tissues.
Being a real lipid mediator of the inflammatory response, it comes into action quickly after the start of the immune response, stimulating the phagocytosis of apoptotic leukocytes and favoring the apoptosis of damaged cells, with a pro-resolutive action on the inflammation that will result also in a consequent reduction of pain. But it doesn't stop there. The mechanisms related to the reduction of inflammation and pain are also related to the ability to bind to some specific receptors activated by peroxisome-alpha proliferators (PPAR-alpha), which are involved in the gene regulation of pain and inflammation.
Artukoglu BB, Beyer C, Zuloff-Shani A, Brener E, Bloch MH. Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis. Pain Physician. 2017 Jul;20(5):353-362. PMID: 28727699.
Gabrielsson L, Mattsson S, Fowler CJ. Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Br J Clin Pharmacol. 2016 Oct;82(4):932-42. doi: 10.1111/bcp.13020. Epub 2016 Jun 29. PMID: 27220803; PMCID: PMC5094513.
Passavanti MB, Alfieri A, Pace MC, Pota V, Sansone P, Piccinno G, Barbarisi M, Aurilio C, Fiore M. Clinical applications of palmitoylethanolamide in pain management: protocol for a scoping review. Syst Rev. 2019 Jan 8;8(1):9. doi: 10.1186/s13643-018-0934-z. PMID: 30621775; PMCID: PMC6323836.
D'Amico R, Impellizzeri D, Cuzzocrea S, Di Paola R. ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain. Int J Mol Sci. 2020 Jul 27;21(15):5330. doi: 10.3390/ijms21155330. PMID: 32727084; PMCID: PMC7432736.
Paladini A, Fusco M, Cenacchi T, Schievano C, Piroli A, Varrassi G. Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis. Pain Physician. 2016 Feb;19(2):11-24. PMID: 26815246.
Paladini A, Fusco M, Coaccioli S, Skaper SD, Varrassi G. Chronic Pain in the Elderly: The Case for New Therapeutic Strategies. Pain Physician. 2015 Sep-Oct;18(5):E863-76. PMID: 26431140.