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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Systemic alterations in plasma proteins from women with chronic widespread pain compared to healthy controls: a proteomic study

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          Abstract

          Chronic widespread pain (CWP) is a complex pain condition that is difficult to treat. The prevalence of CWP approximates ~10% of the general population, with higher prevalence in women. Lack of understanding of molecular mechanisms has been a challenge for diagnosis and treatment of chronic pain. The aim of this study was to explore the systemic protein changes in CWP compared to those in healthy controls (CON). By applying 2-dimensional gel electrophoresis, we analyzed the protein pattern of plasma samples from women with CWP (n=16) and healthy women (n=23). The proteomic data were analyzed using multivariate statistical models, and altered proteins were identified using mass spectrometry. The proteome analysis was further validated by gel-free Western blot. Multivariate statistical data analysis of quantified proteins revealed 22 altered proteins in women with CWP, compared to CON group. Many of the identified proteins are previously known to be involved in different parts of the complement system and metabolic and inflammatory processes, e.g., complement factor B, vitamin D-binding protein, ceruloplasmin, transthyretin and alpha-2-HS-glycoprotein. These results indicate that important systemic protein differences exist between women with CWP and healthy women. Further, this study illustrates the potential use of proteomics to detect biomarkers that may provide new insights into the molecular mechanism(s) of chronic pain. However, further larger investigations are required in order to confirm these findings before it will be possible to identify proteins as potential pain biomarkers for clinical use.

          Most cited references52

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          Trials and tribulations of 'omics data analysis: assessing quality of SIMCA-based multivariate models using examples from pulmonary medicine.

          Respiratory diseases are multifactorial heterogeneous diseases that have proved recalcitrant to understanding using focused molecular techniques. This trend has led to the rise of 'omics approaches (e.g., transcriptomics, proteomics) and subsequent acquisition of large-scale datasets consisting of multiple variables. In 'omics technology-based investigations, discrepancies between the number of variables analyzed (e.g., mRNA, proteins, metabolites) and the number of study subjects constitutes a major statistical challenge. The application of traditional univariate statistical methods (e.g., t-test) to these "short-and-wide" datasets may result in high numbers of false positives, while the predominant approach of p-value correction to account for these high false positive rates (e.g., FDR, Bonferroni) are associated with significant losses in statistical power. In other words, the benefit in decreased false positives must be counterbalanced with a concomitant loss in true positives. As an alternative, multivariate statistical analysis (MVA) is increasingly being employed to cope with 'omics-based data structures. When properly applied, MVA approaches can be powerful tools for integration and interpretation of complex 'omics-based datasets towards the goal of identifying biomarkers and/or subphenotypes. However, MVA methods are also prone to over-interpretation and misuse. A common software used in biomedical research to perform MVA-based analyses is the SIMCA package, which includes multiple MVA methods. In this opinion piece, we propose guidelines for minimum reporting standards for a SIMCA-based workflow, in terms of data preprocessing (e.g., normalization, scaling) and model statistics (number of components, R2, Q2, and CV-ANOVA p-value). Examples of these applications in recent COPD and asthma studies are provided. It is expected that readers will gain an increased understanding of the power and utility of MVA methods for applications in biomedical research.
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            Small fibre pathology in patients with fibromyalgia syndrome.

            Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.
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              Structures of complement component C3 provide insights into the function and evolution of immunity.

              The mammalian complement system is a phylogenetically ancient cascade system that has a major role in innate and adaptive immunity. Activation of component C3 (1,641 residues) is central to the three complement pathways and results in inflammation and elimination of self and non-self targets. Here we present crystal structures of native C3 and its final major proteolytic fragment C3c. The structures reveal thirteen domains, nine of which were unpredicted, and suggest that the proteins of the alpha2-macroglobulin family evolved from a core of eight homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the alpha-chain, including movement of a critical interaction site through a ring formed by the domains of the beta-chain, indicate an unprecedented, conformation-dependent mechanism of activation, regulation and biological function of C3.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2017
                05 April 2017
                : 10
                : 797-809
                Affiliations
                Pain and Rehabilitation Centre, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
                Author notes
                Correspondence: Karin Wåhlén, Pain and Rehabilitation Centre, Department of Medical and Health Sciences, PAINOMICS ® Laboratory, Linköping University, SE-581 85 Linköping, Sweden, Tel +46 10 103 4155, Email karin.wahlen@ 123456liu.se
                Article
                jpr-10-797
                10.2147/JPR.S128597
                5388344
                28435317
                93f107dd-e3ef-4c6d-9808-0dda3cd92181
                © 2017 Wåhlén et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Anesthesiology & Pain management
                inflammation,biomarker,painomics,complement system,gc protein
                Anesthesiology & Pain management
                inflammation, biomarker, painomics, complement system, gc protein

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