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Frequency of Hospitalizations for Pain and Association With Altered Brain Network Connectivity in Sickle Cell Disease

  • Deepika S. Darbari
    Correspondence
    Address reprint requests to Deepika S. Darbari, MD, Division of Hematology, Center for Cancer and Blood Disorders, Children’s National Health System, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, 111 Michigan Avenue NW, Washington, DC 20010.
    Affiliations
    Division of Hematology, Center for Cancer and Blood Disorders, Children’s National Health System, Washington, DC

    Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC

    Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
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  • Johnson P. Hampson
    Affiliations
    Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan
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  • Eric Ichesco
    Affiliations
    Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan
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  • Nadja Kadom
    Affiliations
    Department of Radiology, Boston University Medical Center, Boston, Massachusetts
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  • Gilbert Vezina
    Affiliations
    Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC

    Department of Diagnostic Imaging and Radiology, Children’s National Health System, Washington, District of Columbia
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  • Iordanis Evangelou
    Affiliations
    Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland

    Department of Diagnostic Imaging and Radiology, Children’s National Health System, Washington, District of Columbia
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  • Daniel J. Clauw
    Affiliations
    Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan
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  • James G. Taylor VI
    Affiliations
    Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
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  • Richard E. Harris
    Affiliations
    Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan
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Published:August 17, 2015DOI:https://doi.org/10.1016/j.jpain.2015.07.005

      Highlights

      • Wide variability exists in the frequency of hospitalizations for pain among patients with sickle cell disease.
      • This pilot study explored the association between hospitalizations for pain and intrinsic resting state brain connectivity in the steady state of health.
      • Patients with frequent hospitalizations for pain showed patterns of increased pronociceptive and decreased antinociceptive brain connectivity.

      Abstract

      Sickle cell disease (SCD) is a hemoglobinopathy that affects more than 100,000 individuals in the United States. The disease is characterized by the presence of sickle hemoglobin and recurrent episodes of pain. Some individuals with SCD experience frequent hospitalizations and a high burden of pain. The role of central mechanisms in SCD pain has not been explored. Twenty-five adolescents and young adults with SCD underwent functional magnetic resonance imaging. Participants were stratified into groups with high pain or low pain based on the number of hospitalizations for pain in the preceding 12 months. Resting state functional connectivity was analyzed using seed-based and dual regression independent component analysis. Intrinsic brain connectivity was compared between the high pain and low pain groups, and association with fetal hemoglobin, a known modifier of SCD, was explored. Patients in the high pain group displayed an excess of pronociceptive connectivity such as between anterior cingulate and default mode network structures, such as the precuneus, whereas patients in the low pain group showed more connectivity to antinociceptive structures such as the perigenual and subgenual cingulate. Although a similar proportion of patients in both groups reported that they were on hydroxyurea, the fetal hemoglobin levels were significantly higher in the low pain group and were associated with greater connectivity to antinociceptive structures. These findings support the role of central mechanisms in SCD pain. Intrinsic brain connectivity should be explored as a complementary and objective outcome measure in SCD pain research.

      Perspective

      Altered connectivity patterns associated with high pain experience in patients with sickle cell disease suggest a possible role of central mechanisms in sickle cell pain. Resting state brain connectivity studies should be explored as an effective methodology to investigate pain in SCD.

      Key words

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