A Decades-Long Journey of Palmitoylethanolamide (PEA) for Chronic Neuropathic Pain Management: A Comprehensive Narrative Review

Palmitoylethanolamide (PEA) has been prescribed in neuropathic pain management for over 20 years. This study aims to summarize what has been published on the topic in the last 15 years and determine the appropriateness of the prescribing. It describes the pharmacological aspect of PEA, especially focusing on its pharmacodynamics and pharmacokinetics. Then, it deeply explores why PEA may be useful in the pharmacological management of both neuropathic and mixed pain. Finally, it examines some innovative patent, which aims to address obstacles encountered with conventional PEA formulations, for its pharmacodynamic characteristics. One of them (Equisetum-PEA) seems promising. It partially ameliorates the bioavailability and the targeted distribution. It seems to introduce novel advancements that can potentially enhance the therapeutic effectiveness of PEA in terms of its anti-inflammatory, antioxidant, and analgesic properties. The deep literature analysis aims to examine the potential advantages of PEA, in the context of several pathological conditions that may benefit from this molecule. It focuses on various published data regarding the clinical efficacy of PEA in managing neuropathic and mixed pain. Also, it tries to understand if it can modernize the field of therapy based on PEA, thus offering a better treatment option for individuals with chronic long-term inflammation, oxidative stress, and neuropathic or mixed pain with a neuropathic component. The study examines the possible impact of PEA on personalized medicine strategies and its potential for translation into clinical practice. It analyses the possibilities that PEA has in enhancing patient outcomes in a range of central nervous system and inflammatory conditions. A complete analysis of the therapeutic potentialities of this product was missing. This extensive narrative review makes a valuable contribution to the ongoing comprehension of PEA therapy. It establishes a foundation for further exploration in research and potential uses in clinical settings.