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      Abnormal neuroinflammation in fibromyalgia and CRPS using [ 11C]-(R)-PK11195 PET

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          Abstract

          Purpose

          Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls.

          Methods

          Neuroinflammation was measured as the distribution volume ratio (DVR) of [ 11C]-(R)-PK11195 positron emission tomography (PET) in 12 FM patients, 11 patients with CRPS and 15 healthy controls.

          Results

          Neuroinflammation in FM patients was significantly higher in the left pre (primary motor cortex) and post (primary somatosensory cortex) central gyri (p < 0.001), right postcentral gyrus (p < 0.005), left superior parietal and superior frontal gyri (p < 0.005), left precuneus (p < 0.01), and left medial frontal gyrus (p = 0.036) compared with healthy controls. Furthermore, the DVR of [ 11C]-(R)-PK11195 in FM patients demonstrated decreased neuroinflammation in the medulla (p < 0.005), left superior temporal gyrus (p < 0.005), and left amygdala (p = 0.020) compared with healthy controls.

          Conclusions

          To the authors’ knowledge, this report is the first to describe abnormal neuroinflammation levels in the brains of FM patients compared with that in patients with CRPS using [ 11C]-(R)-PK11195 PET. The results suggested that abnormal neuroinflammation can be an important pathological factor in FM. In addition, the identification of common and different critical regions related to abnormal neuroinflammation in FM, compared with patients with CRPS and healthy controls, may contribute to improved diagnosis and the development of effective medical treatment for patients with FM.

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          Most cited references46

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          The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation.

          The Posttraumatic Stress Disorder Checklist (PCL) is a widely used DSM-correspondent self-report measure of PTSD symptoms. The PCL was recently revised to reflect DSM-5 changes to the PTSD criteria. In this article, the authors describe the development and initial psychometric evaluation of the PCL for DSM-5 (PCL-5). Psychometric properties of the PCL-5 were examined in 2 studies involving trauma-exposed college students. In Study 1 (N = 278), PCL-5 scores exhibited strong internal consistency (α = .94), test-retest reliability (r = .82), and convergent (rs = .74 to .85) and discriminant (rs = .31 to .60) validity. In addition, confirmatory factor analyses indicated adequate fit with the DSM-5 4-factor model, χ2 (164) = 455.83, p < .001, standardized root mean square residual (SRMR) = .07, root mean squared error of approximation (RMSEA) = .08, comparative fit index (CFI) = .86, and Tucker-Lewis index (TLI) = .84, and superior fit with recently proposed 6-factor, χ2 (164) = 318.37, p < .001, SRMR = .05, RMSEA = .06, CFI = .92, and TLI = .90, and 7-factor, χ2 (164) = 291.32, p < .001, SRMR = .05, RMSEA = .06, CFI = .93, and TLI = .91, models. In Study 2 (N = 558), PCL-5 scores demonstrated similarly strong reliability and validity. Overall, results indicate that the PCL-5 is a psychometrically sound measure of PTSD symptoms. Implications for use of the PCL-5 in a variety of assessment contexts are discussed.
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            GPOWER: A general power analysis program

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              The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.

              To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms. We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale. Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI > or =7 AND SS > or =5) OR (WPI 3-6 AND SS > or =9). This simple clinical case definition of fibromyalgia correctly classifies 88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.
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                Author and article information

                Contributors
                Role: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: Writing – original draft
                Role: Data curation
                Role: Data curation
                Role: Writing – review & editing
                Role: Data curation
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Methodology
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 February 2021
                2021
                : 16
                : 2
                : e0246152
                Affiliations
                [1 ] Department of Electronic Engineering, Pai Chai University, Daejeon, Republic of Korea
                [2 ] Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea
                [3 ] Department of Psychiatry, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
                [4 ] Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
                [5 ] Department of Psychiatry, Seoul National University College of Medicine and Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea
                [6 ] Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of Korea
                [7 ] Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
                [8 ] Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
                [9 ] Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
                [10 ] Emotional Information and Communication Technology Association, Seoul, Republic of Korea
                University of Modena and Reggio Emilia, ITALY
                Author notes

                Competing Interests: The authors declare that they have no conflict of interest.

                ‡ GJC and DHK also contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8741-5748
                Article
                PONE-D-20-33063
                10.1371/journal.pone.0246152
                7870009
                33556139
                52375aec-7758-403a-a973-bb024666daec
                © 2021 Seo 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
                : 21 October 2020
                : 15 January 2021
                Page count
                Figures: 5, Tables: 1, Pages: 14
                Funding
                Funded by: Ministry of Health & Welfare
                Award ID: HI14C1072, HI18C1916, and HI14C1135
                Funded by: Ministry of Education
                Award ID: NRF-2016R1D1A1B03930919
                Award Recipient :
                This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1B03930919). Also, this work was supported by intramural research funds from Seoul National University and grants of Korea Health Technology R&D Project through Korea Health Industry Development Institute (KHIDI) funded by Ministry of Health & Welfare (grant number: HI14C1072, HI18C1916, and HI14C1135).
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Neuromuscular Diseases
                Fibromyalgia
                Medicine and Health Sciences
                Neurology
                Neuromuscular Diseases
                Fibromyalgia
                Medicine and Health Sciences
                Rheumatology
                Fibromyalgia
                Biology and Life Sciences
                Physiology
                Sensory Physiology
                Somatosensory System
                Pain Sensation
                Biology and Life Sciences
                Neuroscience
                Sensory Systems
                Somatosensory System
                Pain Sensation
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Pain
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Pain
                Neuropathic Pain
                Biology and Life Sciences
                Anatomy
                Brain
                Amygdala
                Medicine and Health Sciences
                Anatomy
                Brain
                Amygdala
                Biology and Life Sciences
                Anatomy
                Nervous System
                Central Nervous System
                Medicine and Health Sciences
                Anatomy
                Nervous System
                Central Nervous System
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Positron Emission Tomography
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Positron Emission Tomography
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Tomography
                Positron Emission Tomography
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Tomography
                Positron Emission Tomography
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Tomography
                Positron Emission Tomography
                Biology and Life Sciences
                Anatomy
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                Motor Cortex
                Medicine and Health Sciences
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                Motor Cortex
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                All relevant data are within the manuscript and its Supporting Information files.

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