Distribution of an Analgesic Palmitoylethanolamide and Other N-Acylethanolamines in Human Placental Membranes

Abstract

Human amniotic and amniochorionic membranes (AM, ACM) are the most often used grafts accelerating wound healing due to their anti-inflammatory, anti-microbial, anti-fibrotic, and analgesic properties. We assessed the distribution of endogenous fatty acid amides N-acylethanolamines (NAEs): palmitoylethanolamide (PEA), oleoylethanolamide (OEA) and anandamide (AEA) in placental tissues, as they could participate in wound healing properties of AM/ACM grafts. Ten placentas were collected after caesarean delivery. NAEs were detected using ultra-high-performance liquid chromatography-tandem mass spectrometry analysis in fresh samples of AM, ACM, placental disc, umbilical cord, umbilical serum and vernix caseosa), and decontaminated samples of AM and ACM. NAEs were present in all studied tissue types, with mean concentrations in fresh tissues ranging: 76 – 350 (PEA); 31 – 220 (OEA); 7 – 30 ng/g (AEA). The highest mean concentrations were found in AM (PEA: 350 ng/g) or placenta (OEA: 220 ng/g; AEA: 30 ng/g), respectively. Low levels of NAEs were found in serum and vernix. Decontamination of AM, but not ACM, induced a significant (3 – 3.5-fold) increase in the levels of NAEs. PEA is the first compound with direct analgesic effect detected in AM and ACM. We thus propose NAEs, especially PEA, as one of the possible factors responsible for the anti-hyperalgesic, anti-inflammatory and neuroprotective effects of AM/ACM grafts, stimulating their wound healing effect. The increase of NAE levels in AM and ACM after tissue decontamination indicates that tissue processing may play an important role in maintaining the analgesic effect.