Palmitoylethanolamide (PEA) is an endogenous amide fatty acid, an analog of the endocannabinoid anandamide (AEA) which belongs to the N-acylethanolamine family (NAE). In response to noxious stimuli, NAEs are released from the cells. Like all NAEs, PEA also has a local effect, and its tissue levels are closely controlled by the action of production balance and degradation. Two intracellular amidases, expressed in inflammatory cells, have been involved in lipid amide degradation: fatty - acid amide hydrolase (FAAH) and hydrolyzing amidase (NAAA) by N-acylethanolamine.
The effects of PEA powder are related to its association with several pathways: first, it decreases the recruitment and activation of mast cells at nerve injury sites and the release of pro-inflammatory mediators from those cells via the peroxisome proliferator-activated receptor alpha (PPARα); second, it inhibits the activation of microglia and the recruitment of mast cells into the spinal cord after p. Initially, PEA was also supposed to be a cannabinoid type II receptor (CB2) agonist; subsequently, in their research, Sugiura et al. demonstrated that PEA has only a very low affinity for this receptor, clarifying why CB2 antagonists do not inhibit some of its anti-inflammatory effects sible from anandamide degradation (AEA), an agonist of CB1.
A few researchers based on the use of Palmitoylethanolamide in a variety of chronic conditions of pain. For example, it can have a beneficial effect such as adjuvant for treating low back pain or it has been used alone for chronic pain management in critically ill older patients, where the use of traditional analgesics can lead to high risk of adverse effects. Encouraging results in the treatment of non - surgical radiculopathies with ultra-micronized PEA formulation and the combination therapy with alpha-lipoic acid to reduce chronic prostatitis / chronic pelvic pain syndrome have been demonstrated.