Palmitoylethanolamide in the Treatment of Pain and Its Clinical Application Prospects

Abstract Palmitoylethanolamide (PEA) has attracted increasing attention from researchers as an endogenous lipid mediator. It exhibits a unique mechanism of action in alleviating pain, controlling inflammation, and providing neuroprotection. It primarily regulates downstream signaling pathways by activating peroxisome proliferator-activated receptor alpha (PPAR-α) to inhibit the activity of nuclear factor kappa B (NF-κB), thereby reducing the production of pro-inflammatory cytokines. Additionally, PEA interacts synergistically with the endogenous cannabinoid system to modulate neurotransmission by enhancing the function of endogenous cannabinoids. The anti-inflammatory