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

Abstract

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.

The relationship between thalamic GABA content and resting cortical rhythm in neuropathic pain

“…In direct contrast, in this study, in addition to these standard medications, 8 of the 20 pain subjects were taking palmitoylethanolamide (PEA), which has been reported to target the peroxisome proliferator-activated receptor alpha as well as cannabinoid-like Gcoupled receptors (Godlewski, Offertaler, Wagner, & Kunos, 2009;Lo Verme et al, 2005). While we do not have a sample large enough to explore the effects of PEA on thalamic GABA and brain activity, there is some evidence to suggest PEA may reduce neuropathic pain and thus this could have affected the results of this study (Keppel Hesselink & Kopsky, 2015). The effects of medications on thalamic GABA and resting brain activity require further detailed and directed investigations.…”

Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome

“…Palmithoylethanolamide is approved by the Italian Ministry of Health as ‘Food for special medical purposes’ for visceral pain. Dosing of the active treatment in the present study was based on a previous dose‐finding study (although not performed in IBS) . Study visits were conducted every 4 weeks during the treatment period.…”

Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics

“…In the past, it has already been pointed out that non-neuronal cells such as the mast cells cross talk with nerve endings, and this was the basis for the efficacy of the autacoid palmitoylethanolamide (PEA) in various mast cell-related disorders as well as in neuropathic pain 36–38. Nociceptors terminate in the periphery as free nerve endings and can directly be in contact with injured tissue; therefore, any cell in the epidermis can serve as a potential sensory receptor for injury 39.…”