Mechanisms and clinical applications of palmitoylethanolamide (PEA) in the treatment of neuropathic pain

Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject...

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Bibliographic Details
Published in:Inflammopharmacology 2025, Vol.33 (1), p.121-133
Main Authors: Das, Ardra, Balakrishnan, Preetha
Format: Article
Language:English
Subjects:
Allergology
Amides - pharmacology
Analgesics - pharmacology
Analgesics - therapeutic use
Animals
Biomedical and Life Sciences
Biomedicine
Dermatology
Endocannabinoids - metabolism
Ethanolamines - administration & dosage
Ethanolamines - pharmacology
Ethanolamines - therapeutic use
Gastroenterology
Humans
Immunology
Inflammation - drug therapy
Neuralgia - drug therapy
Palmitic Acids - pharmacology
Palmitic Acids - therapeutic use
Pharmacology/Toxicology
Review
Rheumatology
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Summary:Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject of extensive research to elucidate its properties, efficacy, and clinical applications. PEA primarily exerts its effects through interaction with its primary receptor PPAR α, this interaction influences pain signalling pathways and neuroinflammatory processes by modulating the synthesis of pro-inflammatory cytokines, mast cell degranulation, microglial activation, and decrease of oxidative stress. PEA’s interaction with endocannabinoid receptors decreases the inflammatory cytokine and chemokine production and thereby a descending pain sensation. The pharmacological and pharmacokinetic characteristics of PEA are examined in this paper, along with its potential for efficiency when used in in combination additional therapies in a variety of neurodegenerative disease models, including multiple sclerosis, Parkinson's disease, and Alzheimer's. Experimental evidence shows that PEA not only reduces pain and inflammation but also lowers the need for higher dosages of other drugs hence minimizing the risk of drug toxicity. The bioavailability of PEA has been enhanced by recent technological developments, which emphasize continuous research efforts to maximize PEA's therapeutic potential in pain treatment and associated medical sectors. Graphical Abstract
ISSN:0925-4692
1568-5608
1568-5608
DOI:10.1007/s10787-024-01623-8