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Palmitoylethanolamide (PEA) is an endogenous lipid modulator in animals and humans, and has been evaluated since the 1970s as an anti-inflammatory and analgesic drug in more than 30 clinical trials, in a total of ~6,000 patients. PEA is currently available worldwide as a nutraceutical in different formulations, with and without excipients. Here we describe the results of all clinical trials evaluating PEA's efficacy and safety in nerve compression syndromes: sciatic pain and pain due to carpal tunnel syndrome, and review preclinical evidence in nerve impingement models. Both the pharmacological studies as well as the clinical trials supported PEA's action as an analgesic compound. In total, eight clinical trials have been published in such entrapment syndromes, and 1,366 patients have been included in these trials. PEA proved to be effective and safe in nerve compression syndromes. In one pivotal, double blind, placebo controlled trial in 636 sciatic pain patients, the number needed to treat to reach 50% pain reduction compared to baseline was 1.5 after 3 weeks of treatment. Furthermore, no drug interactions or troublesome side effects have been described so far. Physicians are not always aware of PEA as a relevant and safe alternative to opioids and co-analgesics in the treatment of neuropathic pain. Especially since the often prescribed co-analgesic pregabaline has been proven to be ineffective in sciatic pain in a double blind enrichment trial, PEA should be considered as a new and safe treatment option for nerve compression syndromes.

Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome