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      Whole blood transcriptomic profiles can differentiate vulnerability to chronic low back pain

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          Abstract

          The mechanisms underlying the transition from acute to chronic pain remain unclear. Here, we sought to characterize the transcriptome associated with chronic low back pain as well as the transcriptome of the transition from acute to chronic low back pain. For the analysis, we compared the whole blood transcriptome of: (a) patients at the onset of low back pain who no longer had pain within 6 weeks after onset (acute) with patients who developed chronic low back pain at 6 months (chronic T5); and, (b) patients at the onset of low back pain (chronic T1) who developed chronic pain at 6 months with healthy pain-free (normal) controls. The majority of differentially expressed genes were protein coding. We illustrate a unique chronic low back pain transcriptome characterized by significant enrichment for known pain genes, extracellular matrix genes, and genes from the extended major histocompatibility complex (MHC) genomic locus. The transcriptome of the transition from acute to chronic low back pain was characterized by significant upregulation of antigen presentation pathway (MHC class I and II) genes and downregulation of mitochondrial genes associated with oxidative phosphorylation, suggesting a unique genomic signature of vulnerability to low back pain chronicity.

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          The short-form McGill Pain Questionnaire.

          A short form of the McGill Pain Questionnaire (SF-MPQ) has been developed. The main component of the SF-MPQ consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. Three pain scores are derived from the sum of the intensity rank values of the words chosen for sensory, affective and total descriptors. The SF-MPQ also includes the Present Pain Intensity (PPI) index of the standard MPQ and a visual analogue scale (VAS). The SF-MPQ scores obtained from patients in post-surgical and obstetrical wards and physiotherapy and dental departments were compared to the scores obtained with the standard MPQ. The correlations were consistently high and significant. The SF-MPQ was also shown to be sufficiently sensitive to demonstrate differences due to treatment at statistical levels comparable to those obtained with the standard form. The SF-MPQ shows promise as a useful tool in situations in which the standard MPQ takes too long to administer, yet qualitative information is desired and the PPI and VAS are inadequate.
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            Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study

            Objective Low back pain (LBP) is a common musculoskeletal disorder, but it is still unclear which individuals develop it. The authors examined the contribution of genetic factors, lumbar disc degeneration (LDD) and other risk factors in a female sample of the general population. Material and Methods A cross-sectional study was conducted among 2256 women (371 and 698 monozygotic and dizygotic twin pairs and 29 sibling pairs and 60 singletons) with a mean age of 50 years (18–84). A self-reported validated questionnaire was used to collect back pain data. Risk factors including body weight, smoking, occupation, physical exercise and MRI assessed LDD were measured. Data analysis included logistic regression and variance decomposition. Results The major factors associated with LBP included genetic background, with OR approximately 6 if the monozygotic co-twin had LBP, or 2.2 if she was a dizygotic co-twin. In addition, LDD and overweight were highly significantly (p<0.001) associated with non-specific LBP. The single most important risk factor was the amount of LDD. After adjustment for other risk factors, the individuals who exhibited advanced LDD (90% vs 10%) had 3.2 higher odds of manifesting LBP. The data also showed a significant (p<0.001) genetic correlation between the LBP and LDD measurements, suggesting that approximately 11–13% of the genetic effects are shared by LDD and LBP. Conclusions The main risk factors for reported episodes of severe and disabling LBP in UK women include the degree of LDD as assessed by MRI, being overweight and genetic heritability.
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              Opioids for low back pain

              Back pain affects most adults, causes disability for some, and is a common reason for seeking healthcare. In the United States, opioid prescription for low back pain has increased, and opioids are now the most commonly prescribed drug class. More than half of regular opioid users report back pain. Rates of opioid prescribing in the US and Canada are two to three times higher than in most European countries. The analgesic efficacy of opioids for acute back pain is inferred from evidence in other acute pain conditions. Opioids do not seem to expedite return to work in injured workers or improve functional outcomes of acute back pain in primary care. For chronic back pain, systematic reviews find scant evidence of efficacy. Randomized controlled trials have high dropout rates, brief duration (four months or less), and highly selected patients. Opioids seem to have short term analgesic efficacy for chronic back pain, but benefits for function are less clear. The magnitude of pain relief across chronic non-cancer pain conditions is about 30%. Given the brevity of randomized controlled trials, the long term effectiveness and safety of opioids are unknown. Loss of long term efficacy could result from drug tolerance and emergence of hyperalgesia. Complications of opioid use include addiction and overdose related mortality, which have risen in parallel with prescription rates. Common short term side effects are constipation, nausea, sedation, and increased risk of falls and fractures. Longer term side effects may include depression and sexual dysfunction. Screening for high risk patients, treatment agreements, and urine testing have not reduced overall rates of opioid prescribing, misuse, or overdose. Newer strategies for reducing risks include more selective prescription of opioids and lower doses; use of prescription monitoring programs; avoidance of co-prescription with sedative hypnotics; and reformulations that make drugs more difficult to snort, smoke, or inject.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Writing – original draft
                Role: Formal analysisRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 May 2019
                2019
                : 14
                : 5
                : e0216539
                Affiliations
                [1 ] Department of Pain & Translational Symptom Science and Center to Advance Chronic Pain Research, University of Maryland School of Nursing, Baltimore, Maryland, United States of America
                [2 ] University of Delaware School of Nursing, Newark, Delaware, United States of America
                [3 ] Graduate Program in Life Sciences Molecular Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
                [4 ] Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
                [5 ] Department of Pathology Division of Molecular Diagnostics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America
                [6 ] Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, United States of America
                [7 ] University of Florida Gainesville College of Nursing, Gainesville, Florida, United States of America
                [8 ] Center for Advancement in Managing Pain, University of Connecticut School of Nursing, Storrs, Connecticut, United States of America
                Universidad de Jaen, SPAIN
                Author notes

                Competing Interests: SGD, CLR, MG, and ARS have a patent pending (62/607,969 filed 12/20/17) on Biomarkers of Acute and Chronic Pain. The other authors declare no competing interests.

                Author information
                http://orcid.org/0000-0001-6764-9347
                http://orcid.org/0000-0001-7168-0144
                Article
                PONE-D-18-31916
                10.1371/journal.pone.0216539
                6522025
                31095601
                142e6975-24fd-42c3-89ca-dde61e271582

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 5 November 2018
                : 23 April 2019
                Page count
                Figures: 7, Tables: 1, Pages: 20
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100005349, National Institutes of Health;
                Award ID: NR013932
                Award Recipient :
                This research was funded by the National Institute of Nursing Research (ARS, PI; R01 NR013932; SGD, PI; P30 NR011396; R01 NR013601; P30 NR014129) at www.nih.gov. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research (NINR) or the National Institutes of Health (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the remaining authors, none were declared.
                Categories
                Research Article
                Biology and Life Sciences
                Genetics
                Gene Expression
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Pain
                Lower Back Pain
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Pain
                Lower Back Pain
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                Clinical Medicine
                Clinical Immunology
                Major Histocompatibility Complex
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                Custom metadata
                Data cannot be shared publicly because the participants did not consent for public sharing. Data are available from the Pain and Comorbid Symptoms Consortium Data Access Committee (contact via painresearch@ 123456uconn.edu ) for interested researchers.

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