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The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
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2017 (English)In: Pharmacology Research & Perspectives, E-ISSN 2052-1707, Vol. 5, no 2, article id e00300Article in journal (Refereed) Published
Abstract [en]

The anti-inflammatory agent palmitoylethanolamide (PEA) reduces cyclooxygenase (COX) activity in vivo in a model of inflammatory pain. It is not known whether the compound reduces prostaglandin production in RAW264.7 cells, whether such an action is affected by compounds preventing the breakdown of endogenous PEA, whether other oxylipins are affected, or whether PEA produces direct effects upon the COX-2 enzyme. RAW264.7 cells were treated with lipopolysaccharide and interferon-c to induce COX-2. At the level of mRNA, COX-2 was induced > 1000-fold following 24 h of the treatment. Coincubation with PEA (10 mu mol/L) did not affect the levels of COX-2, but reduced the levels of prostaglandins D-2 and E-2 as well as 11- and 15-hydroxyeicosatetraenoic acid, which can also be synthesised by a COX-2 pathway in macrophages. These effects were retained when hydrolysis of PEA to palmitic acid was blocked. Linoleic acidderived oxylipin levels were not affected by PEA. No direct effects of PEA upon the oxygenation of either arachidonic acid or 2-arachidonoylglycerol by COX-2 were found. It is concluded that in lipopolysaccharide and interferon-c-stimulated RAW264.7 cells, PEA reduces the production of COX-2-derived oxylipins in a manner that is retained when its metabolism to palmitic acid is inhibited.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017. Vol. 5, no 2, article id e00300
Keywords [en]
Palmitoylethanolamide, cyclooxygenase, prostaglandin, oxylipin, RAW264.7 cells, fatty acid amide drolase, N-acylethanolamine hydrolysing acid amidase, bootstrapped linear model
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:umu:diva-140988DOI: 10.1002/prp2.300ISI: 000407444900009PubMedID: 28357126Scopus ID: 2-s2.0-85021909304OAI: oai:DiVA.org:umu-140988DiVA, id: diva2:1152469
Funder
Swedish Research Council, 12158Available from: 2017-10-25 Created: 2017-10-25 Last updated: 2023-03-23Bibliographically approved
In thesis
1. Chronic pain: from the study of student attitudes and preferences to the in vitro investigation of a novel treatment strategy
Open this publication in new window or tab >>Chronic pain: from the study of student attitudes and preferences to the in vitro investigation of a novel treatment strategy
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chronic pain will affect one in five adults during their lifetime, and it exerts a heavy burden on society with major physiological, psychological, social, and economic impacts. The current chronic pain curriculum taught to medical students in most settings is fragmented, inconsistent and inadequate and a vast majority of general practitioners considered their undergraduate training in chronic pain incomplete. Attitudes and beliefs amongst health care personnel are important and have shown to have impact on clinical management. There is currently a knowledge gap that needs to be addressed in this matter. In this thesis, through an online survey, the attitudes and beliefs of medical students in Sweden and Australia were surveyed. Additionally, we explored which factors influence chronic pain management amongst medical students in Sweden and Australia and Swedish general practitioners. We found that Swedish final year students have a more positive attitude towards chronic pain patients compared to Australian students. Both student cohorts perceived chronic pain management education in need of improvement. Furthermore, we found that the relative importance of factors that influence treatment decisions are formed early during undergraduate training, which further underlines the importance of improving pain curricula during undergraduate medical education in order to give the emerging workforce appropriate tools to manage chronic pain.

Management of chronic pain urgently requires novel, well-tolerated pharmacological treatment strategies. Palmitoylethanolamide (PEA) is a potential candidate for managing chronic pain. Its analgesic and anti-inflammatory effects have been observed in a range of experimental animal models and clinical trials. However, questions remain as to how PEA exerts its effects and how levels of PEA and its congeners are changed in states of pain and inflammatory disorders in humans. Treatment with PEA decreases cyclooxygenase 2 (COX-2) activity in animal models, but we found that PEA did not have direct effects upon the kinetic properties of COX-2 in a cell free system. However, COX-2 derived eicosanoid levels were reduced by PEA in lipopolysaccharide and interferon-g-stimulated RAW 264.7 cells. With respect to changes in PEA levels in a chronic inflammatory disorder, we investigated PEA levels, in addition to its synthesizing and hydrolysing enzymes in biopsies from patients with oral lichen planus (OLP). We found that the ratio of prostaglandins to PEA was increased in the OLP biopsy samples. Furthermore, PTGS2 mRNA levels (coding for COX-2) were increased in OLP-patients compared to controls relative to NAPEPLD mRNA levels (coding for a key enzyme in the synthesis of PEA). These results suggest that there is a relative deficit of PEA in OLP, raising the possibility that PEA might be useful for the treatment of this disorder.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2020. p. 96
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2085
Keywords
HC-PAIRS, best-worst scaling, palmitoylethanolamine, N-acylthanolamines, oral lichen planus, prostaglandins, chronic pain, prolonged pain, chronic pain education, chronic pain management, medical students, attitudes
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-173854 (URN)978-91-7855-268-9 (ISBN)978-91-7855-267-2 (ISBN)
Public defence
2020-09-11, Triple Helix, Samverkanshuset, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2020-08-21 Created: 2020-08-03 Last updated: 2020-08-10Bibliographically approved

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Gabrielsson, LindaGouveia-Figueira, SandraHäggström, JennyAlhouayek, MireilleFowler, Christopher J.

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