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      Vasopressin SNP pain factors and stress in sickle cell disease

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          Abstract

          Purpose

          Frequencies of single nucleotide polymorphisms (SNPs) from pain related candidate genes are available for individuals with sickle cell disease (SCD). One of those genes, the arginine vasopressin receptor 1A gene (AVPR1A) and one of its SNPs, rs10877969, has been associated with pain and disability in other pain populations. In patients with SCD, clinical factors such as pain and stress have been associated with increased health care utilization, but it is not known if the presence of the AVPR1A SNP plays a role in this observation. The study purpose was to explore the relationships between rs10877969 and self-reported pain, stress, and acute care utilization events among individuals with SCD.

          Methods

          In a cross-sectional investigation of outpatients with SCD, participants completed PAIN ReportIt ®, a computerized pain measure, to describe their pain experience and contributed blood or saliva samples for genetic analysis. We extracted emergency department and acute care utilization from medical records.

          Results

          The SNP genotype frequencies (%) for this sample were CC 30 (28%), CT 44 (41%), TT 33 (31%). Acute care utilization and stress as an aggravator of pain were significantly associated with the rs10877969 genotype ( p = .02 and p = .002, respectively). The CT genotype had the highest mean utilization and CC genotype was associated with not citing stress as a pain aggravator. Chronic pain was not associated with rs10877969 ( p = .41).

          Conclusion

          This study shows that rs10877969 is related to indicators of stress and acute pain. Further research is recommended with other measures of stress and acute pain.

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          Most cited references28

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          Acute care utilization and rehospitalizations for sickle cell disease.

          Published rates of health care utilization and rehospitalization by people with sickle cell disease have had limited generalizability and are not population based. To provide benchmark data for rates of acute care utilization and rehospitalizations for patients with sickle cell disease. Retrospective cohort of sickle cell disease-related emergency department (ED) visits and hospitalizations from select states in the 2005 and 2006 Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases and State Emergency Department Databases. Eight geographically dispersed states (Arizona, California, Florida, Massachusetts, Missouri, New York, South Carolina, and Tennessee) that provide encrypted identifiers and have sufficient numbers of patients with sickle cell disease; together these states have 33% of the US population with sickle cell disease. A total of 21,112 patients with sickle cell-related treat-and-release ED visits or inpatient hospitalizations. Rates of acute care utilization and rehospitalizations. Population-based utilization rates were also calculated. The 21,112 people with sickle cell disease had 109,344 encounters, a mean of 2.59 (95% confidence interval [CI], 2.53-2.65) encounters per patient per year, 1.52 (95% CI, 1.48-1.55) encounters for hospitalizations and 1.08 (95% CI, 1.04-1.11) for treat-and-release ED visits. Utilization was highest for 18- to 30-year-olds, 3.61 (95% CI, 3.47-3.75) encounters per patient per year, and those with public insurance, 3.22 (95% CI, 3.13-3.31) encounters per patient per year. Publicly insured 18- to 30-year-olds had 4.80 (95% CI, 4.58-5.02) encounters per patient per year. Approximately 29% of the population had no encounters while 16.9% had 3 or more encounters per year. The 30-day and 14-day rehospitalization rates were 33.4% (95% CI, 33.0%-33.8%) and 22.1% (95% CI, 21.8%-22.4%), respectively. The rehospitalization rate was highest for 18- to 30-year-olds, with 41.1% (95% CI, 40.5%-41.7%) rehospitalized within 30 days and 28.4% (95% CI, 27.8%-29.0%) within 14 days. Rehospitalizations were also highest for publicly insured patients. Among patients with sickle cell disease, acute care encounters and rehospitalizations were frequent, particularly for 18- to 30-year-olds.
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            Pain genetics: past, present and future.

            Chronic pain is a classic example of gene × environment interaction: inflammatory and/or nerve injuries are known or suspected to be the etiology of most chronic pain syndromes, but only a small minority of those subjected to such injuries actually develop chronic pain. Once chronic pain has developed, pain severity and analgesic response are also highly variable among individuals. Although animal genetics studies have been ongoing for over two decades, only recently have comprehensive human twin studies and large-scale association studies been performed. Here, I review recent and accelerating progress in, and continuing challenges to, the identification of genes contributing to such variability. Success in this endeavor will hopefully lead to both better management of pain using currently available therapies and the development and/or prioritizing of new ones. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament.

              While a variety of cultural, psychological and physiological factors contribute to variability in both clinical and experimental contexts, the role of genetic factors in human pain sensitivity is increasingly recognized as an important element. This study was performed to evaluate genetic influences on variability in human pain sensitivity associated with gender, ethnicity and temperament. Pain sensitivity in response to experimental painful thermal and cold stimuli was measured with visual analogue scale ratings and temperament dimensions of personality were evaluated. Loci in the vanilloid receptor subtype 1 gene (TRPV1), delta opioid receptor subtype 1 gene (OPRD1) and catechol O-methyltransferase gene (COMT) were genotyped using 5' nuclease assays. A total of 500 normal participants (306 females and 194 males) were evaluated. The sample composition was 62.0% European American, 17.4% African American, 9.0% Asian American, and 8.6% Hispanic, and 3.0% individuals with mixed racial parentage. Female European Americans with the TRPV1 Val(585) Val allele and males with low harm avoidance showed longer cold withdrawal times based on the classification and regression tree (CART) analysis. CART identified gender, an OPRD1 polymorphism and temperament dimensions of personality as the primary determinants of heat pain sensitivity at 49 degrees C. Our observations demonstrate that gender, ethnicity and temperament contribute to individual variation in thermal and cold pain sensitivity by interactions with TRPV1 and OPRD1 single nucleotide polymorphisms.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: ResourcesRole: SoftwareRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: VisualizationRole: 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
                11 November 2019
                2019
                : 14
                : 11
                : e0224886
                Affiliations
                [1 ] Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville, Florida, United States of America
                [2 ] Center for Palliative Care Research and Education, University of Florida College of Nursing, Gainesville, Florida, United States of America
                [3 ] Department of Biobehavioral Nursing Science, University of Florida College of Nursing, Gainesville, Florida, United States of America
                [4 ] Department of Biobehavioral Health Sciences, University of Illinois at Chicago College of Nursing, Chicago, Illinois, United States of America
                [5 ] Committee on Clinical Pharmacology and Pharmacogenetics, University of Chicago, Chicago, Illinois, United States of America
                [6 ] Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America
                [7 ] Cancer Center, University of Illinois at Chicago, Chicago, Illinois, United States of America
                [8 ] Division of Hematology/Oncology, University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America
                [9 ] Jessie Brown Veteran’s Administration Medical Center, Chicago, Illinois, United States of America
                University of Mississippi Medical Center, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-8117-3445
                http://orcid.org/0000-0003-3623-7395
                Article
                PONE-D-19-15399
                10.1371/journal.pone.0224886
                6844466
                31710639
                d0e2738e-9f2a-4cd4-b4c0-c4e7744bfea0
                © 2019 Powell-Roach 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
                : 19 June 2019
                : 23 October 2019
                Page count
                Figures: 2, Tables: 2, Pages: 10
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: R01HL124945S
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
                Award ID: T32AG049673
                Award Recipient :
                Funded by: NIDCR
                Award ID: T32DE018381
                Award Recipient :
                Funded by: Sickle Cell Scholar
                Award ID: U54HL117658
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: R01HL124945
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: R01HL124945
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: R01HL124945
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000867, Robert Wood Johnson Foundation;
                Award ID: Future of Nursing Scholar
                Award Recipient :
                The study was approved by the Institutional Review Boards at the University of Illinois at Chicago and the University of Florida. The IRB numbers for this manuscript are: QST: 2014-0287 and SC PAIN: 2006-0266. All participants for this study provided written informed consent. The study was supported by grant numbers R01HL12495, R01HL124945S, R01HL1249451, U54HL117658 for the National Institutes of Health, National Heart Lung & Blood Institute (NHLBI), T32AG049673 from the National Institutes of Aging (NIA), T32DE018381 National Institute of Dental and Craniofacial Research (NIDCR), and the Robert Wood Johnson Future of Nursing Scholars Program. Its contents are solely the responsibility of authors and do not necessarily represent the official views of the NIH, NHLBI, NIA, NIDCR, or the Robert Wood Johnson foundation. The final peer-reviewed manuscript is subject to the National Institutes of Health Public Access Policy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Genetics
                Molecular Genetics
                Biology and Life Sciences
                Molecular Biology
                Molecular Genetics
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Psychological Stress
                Biology and Life Sciences
                Psychology
                Psychological Stress
                Social Sciences
                Psychology
                Psychological Stress
                People and places
                Population groupings
                Ethnicities
                African American people
                Biology and Life Sciences
                Biochemistry
                Hormones
                Peptide Hormones
                Vasopressin
                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Amino Acids
                Basic Amino Acids
                Arginine
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Amino Acids
                Basic Amino Acids
                Arginine
                Biology and Life Sciences
                Biochemistry
                Proteins
                Amino Acids
                Basic Amino Acids
                Arginine
                Medicine and Health Sciences
                Health Care
                Patients
                Outpatients
                Medicine and Health Sciences
                Clinical Genetics
                Genetic Diseases
                Autosomal Recessive Diseases
                Sickle Cell Disease
                Medicine and Health Sciences
                Hematology
                Hemoglobinopathies
                Sickle Cell Disease
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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