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Abstract
The use of cannabinoids to treat fibrotic skin diseases is an emergent issue. Therefore, we aimed to evaluate systemic and skin endocannabinoid responses in the wound-healing process in humans. A prospective study was performed in 50 patients who underwent body-contouring surgery. Anandamide (N-arachidonoylethanolamine, AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were quantified using LC–MS/MS. Ten (20%) patients developed hypertrophic (HT) scars. No significant changes were observed between the normal (N) scar and HT scar groups in terms of plasma and skin endocannabinoids. Nevertheless, a positive correlation between plasma and skin AEA concentrations was found in the N group (r = 0.38, p = 0.015), which was absent in the HT group. Moreover, the AEA concentration was significantly lower in HT scar tissue than in normal scar tissue (0.77 ± 0.12 ng/g vs 1.15 ± 0.15 ng/g, p < 0.001). Interestingly, in all patients, the surgical intervention produced a time-dependent effect with a U shape for AEA, PEA and OEA plasma concentrations. In contrast, 2-AG plasma concentrations increased 5 days after surgery and were reduced and stabilized 3 months later. These results suggest crosstalk between systemic and local skin endocannabinoid systems during human wound healing. AEA appears to be the most likely candidate for this link, which is deficient in patients with HT scars.
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1 University of Porto and Centro Hospitalar São João, EPE, Department of Plastic, Reconstructive and Aesthetic Surgery and Burn Unit, Faculty of Medicine, Porto, Portugal (GRID:grid.435541.2) (ISNI:0000 0000 9851 304X); University of Porto, Department of Biomedicine - Pharmacology and Therapeutics Unit, Faculty of Medicine, Porto, Portugal (GRID:grid.5808.5) (ISNI:0000 0001 1503 7226)
2 University of Porto, Department of Biomedicine - Pharmacology and Therapeutics Unit, Faculty of Medicine, Porto, Portugal (GRID:grid.5808.5) (ISNI:0000 0001 1503 7226)
3 University of Porto, Department of Biomedicine - Pharmacology and Therapeutics Unit, Faculty of Medicine, Porto, Portugal (GRID:grid.5808.5) (ISNI:0000 0001 1503 7226); Universidade do Porto, MedInUP–Centro de Investigação Farmacológica E Inovação Medicamentosa, Porto, Portugal (GRID:grid.5808.5) (ISNI:0000 0001 1503 7226)
4 BIAL-Portela & Cª., S.A., Laboratory of Pharmacology, Department of Research and Development, Trofa, Portugal (GRID:grid.453348.d) (ISNI:0000 0001 0596 2346)
5 University of Porto and Centro Hospitalar São João, EPE, Department of Plastic, Reconstructive and Aesthetic Surgery and Burn Unit, Faculty of Medicine, Porto, Portugal (GRID:grid.435541.2) (ISNI:0000 0000 9851 304X)