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Professor Rita Levi-Montalcini on Nerve Growth Factor, Mast Cells and Palmitoylethanolamide, an Endogenous Anti-Inflammatory and Analgesic Compound

Jan M. Keppel Hesselink

Professor Rita Levi-Montalcini discovered Nerve Growth Factor (NGF) in 1954, and many papers are published since, relating to this tremendously important milestone for the medical sciences. Much less is known about another milestone in molecular and clinical neurology she and her co-workers achieved. In the period 1993-1996 her group identified the mechanism of action of the anti-inflammatory and analgesic properties activity of the endogenous fatty amide palmitoylethanolamide (PEA). PEA is a molecule with tissue-protective and anti-inflammatory activities, widely present in plants, animals and man. Rita Levi-Montalcini and her group discovered in 1993 PEA as a natural modulator of hyperactive mast cells, counteracting the pro-inflammatory actions of NGF. PEA however, has not been registered as pharmaceutical drug, due to the fact that patent protection of the pure and natural compound was impossible. Therefore, developed as a nutraceutical, it did not catch the attention of the medical community, which we hope to prove is incorrect. Based on Levi-Montalcini’s work in the 90s PEA is now available as a nutraceutical for indications related to chronic pain and chronic inflammation. In the period 1970-1980 its safety and efficacy has been explored and documented in 6 double blind clinical trials in flu and respiratory infections in around 2000 patients. Triggered by the findings of Levi-Montalcini PEA has been evaluated since 1993 in a variety of pain indications such as sciatic pain, low back pain, diabetic pain, neuropathic pain, pain due to arthritis in a total of 2000 patients. PEA is therefore most probably the best-documented nutraceutical around, and its pharmacological profile has been described in more than 350 scientific papers. In this review we will discuss Levi-Montalcini’s discovery of PEA’s mechanisms of action and its clinical relevance.