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      High Levels of N-Palmitoylethanolamide and N-Stearoylethanolamide in Microdialysate Samples from Myalgic Trapezius Muscle in Women

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          Abstract

          Background

          N-acylethanolamines (NAEs) are endogenous compounds that regulate inflammation and pain. These include the cannabinoid ligand anandamide (AEA) and the peroxisome proliferator-activated receptor-α ligand palmitoylethanolamide (PEA). Little is known as to the levels of NAEs in pain states in human, particularly in the skeletal muscle. The aim of this study was to investigate the levels of these lipid mediators in muscle dialysate from women with chronic neck-/shoulder pain compared to healthy controls.

          Methods

          Eleven women with chronic neck-/shoulder pain and eleven healthy women participated in this study. All participants went through microdialysis procedures in the trapezius muscle. Muscle dialysate samples were collected during four hours and analysed by nano liquid chromatography tandem mass spectrometry (nLC-MS/MS).

          Results

          We were able to detect AEA, PEA, N-stearoylethanolamine (SEA) and 2-arachidonoylglycerol (2-AG) in a single chromatographic run. Of the NAEs studied, PEA and SEA were clearly detectable in the muscle microdialysate samples. The muscle dialysate levels of PEA and SEA were significantly higher in myalgic subjects compared to healthy controls.

          Conclusion

          This study demonstrates that microdialysis in combination with mass spectrometry can be used for analysing NAE's in human muscle tissue regularly over time. Furthermore the significant group differences in the concentration of PEA and SEA in this study might fill an important gap in our knowledge of mechanisms in chronic myalgia in humans. In the long run this expanded understanding of nociceptive and anitinociceptive processes in the muscle may provide a base for ameliorating treatment and rehabilitation of pain.

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          Most cited references41

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          The need for a new medical model: a challenge for biomedicine.

          The dominant model of disease today is biomedical, and it leaves no room within tis framework for the social, psychological, and behavioral dimensions of illness. A biopsychosocial model is proposed that provides a blueprint for research, a framework for teaching, and a design for action in the real world of health care.
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            The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide.

            Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through an as-yet-uncharacterized mechanism. Here, we identify the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) as the molecular target responsible for the anti-inflammatory properties of PEA. PEA selectively activates PPAR-alpha in vitro with an EC(50) value of 3.1 +/- 0.4 microM and induces the expression of PPAR-alpha mRNA when applied topically to mouse skin. In two animal models, carrageenan-induced paw edema and phorbol ester-induced ear edema, PEA attenuates inflammation in wild-type mice but has no effect in mice deficient in PPAR-alpha. The natural PPAR-alpha agonist oleoylethanolamide (OEA) and the synthetic PPAR-alpha agonists GW7647 and Wy-14643 mimic these effects in a PPAR-alpha-dependent manner. These findings indicate that PPAR-alpha mediates the anti-inflammatory effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its analog OEA, as an endogenous ligand of PPAR-alpha.
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              Understanding the co-occurrence of anxiety disorders and chronic pain: state-of-the-art.

              The purpose of this article is to describe the current state-of-the-art regarding the co-occurrence of the anxiety disorders and chronic pain. First, we describe the core characteristics of chronic pain and its co-occurrence with the anxiety disorders. Second, we review data on the prevalence of co-occurrence. Third, we describe the mutual maintenance and shared vulnerability models, both of which have been offered to explain the co-occurrence of posttraumatic stress disorder (PTSD) and chronic pain and may have applicability to various other anxiety disorders. Fourth, we provide an integrative review of available research addressing the postulates of these models specific to the mechanisms of anxiety sensitivity, selective attention to threat, and reduced threshold for alarm. We conclude with general recommendations for improving assessment and treatment of patients who present with an anxiety disorder accompanied by clinically significant pain. Given that most of the available evidence has come from studies of PTSD and chronic pain, we provide a detailed agenda for future investigation of the co-occurrence of chronic pain and other anxiety disorders.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                18 November 2011
                : 6
                : 11
                : e27257
                Affiliations
                [1 ]Rehabilitation Medicine, Faculty of Health Sciences, Linköping University, and Pain and Rehabilitation Centre, County Council of Östergötland, Linköping, Sweden
                [2 ]Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden
                [3 ]Occupational and Environmental medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, and Department of Occupational and Environmental Medicine, County Council of Östergötland, Linköping, Sweden
                [4 ]Cell Biology, Faculty of Health Sciences, Linköping University, Linköping, Sweden
                Sapienza University of Rome, Italy
                Author notes

                Conceived and designed the experiments: NG B. Ghafouri BL MT LK CJF B. Gerdle. Performed the experiments: NG B. Ghafouri BL LK MVT. Analyzed the data: NG BL CJF B. Gerdle B. Ghafouri MT. Contributed reagents/materials/analysis tools: B. Ghafouri. Wrote the paper: NG BL B. Ghafouri B. Gerdle CJF. Revised different versions of the manuscript: LK MVT.

                Article
                PONE-D-11-10360
                10.1371/journal.pone.0027257
                3220690
                22125609
                55c7b0a5-c1c9-4b6f-943a-18f08b7569f7
                Ghafouri et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 9 June 2011
                : 12 October 2011
                Page count
                Pages: 8
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Musculoskeletal System
                Muscle
                Immunology
                Immunity
                Inflammation
                Proteomics
                Spectrometric Identification of Proteins
                Chemistry
                Chromatography
                Medicine
                Anatomy and Physiology
                Musculoskeletal System
                Muscle
                Physiological Processes
                Anesthesiology
                Pain Management
                Clinical Immunology
                Immunity
                Inflammation
                Clinical Research Design
                Epidemiology
                Physiotherapy and Rehabilitation
                Rheumatology

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                Uncategorized

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