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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald

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Volume 17, Issue 1

Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia

Deepika S. Darbari
  • Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
  • Center for Cancer and Blood Diseases, Children’s National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
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 / Kathleen J. Vaughan
  • Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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 / Katherine Roskom
  • Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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 / Cassie Seamon
  • Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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 / Lena Diaw
  • Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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 / Meghan Quinn
  • Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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 / Anna Conrey
  • Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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  • De Gruyter OnlineGoogle Scholar
 / Alan N. Schechter
  • Molecular Biology and Genetics Section, Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
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 / Jennifer A. Haythornthwaite
  • Center for Mind-Body Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA
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 / Myron A. Waclawiw
  • Office of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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 / Gwenyth R. Wallen / Inna Belfer
  • Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
  • Office of Research on Women’s Health, National Institutes of Health, Bethesda, MD, USA
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 / James G. Taylor VI
  • Corresponding author
  • Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
  • Department of Medicine and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, USA
  • Email
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Published Online: 2017-10-01 | DOI: https://doi.org/10.1016/j.sjpain.2017.08.001

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Abstract

Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored. We hypothesized that adults with SCA would show evidence of central sensitization as observed in other diseases of chronic pain.

Methods

We conducted a prospective study of static and dynamic quantitative sensory tests in 30 adults with SCA and 30 matched controls.

Results

Static thermal testing using cold stimuli showed lower pain thresholds (p = 0.04) and tolerance (p = 0.04) in sickle cell subjects, but not for heat. However, SCA subjects reported higher pain ratings with random heat pulses (p < 0.0001) and change in scores with temporal summation at the heat pain threshold (p = 0.002). Similarly, with the use of pressure pain stimuli, sickle cell subjects reported higher pain ratings (p = 0.04), but not higher pressure pain tolerance/thresholds or allodynia to light tactile stimuli. Temporal summation pain score changes using 2 pinprick probes (256 and 512 mN) were significantly greater (p = 0.004 and p = 0.008) with sickle cell, and delayed recovery was associated with lower fetal hemoglobin (p = 0.002 and 0.003).

Conclusions

Exaggerated temporal summation responses provide evidence of central sensitization in SCA.

Implications

The association with fetal hemoglobin suggests this known SCA modifier may have a therapeutic role in modulating central sensitization.

This article offers supplementary material which is provided at the end of the article.

Keywords: Sickle cell anemia; Pain; Central sensitization; Temporal summation; Fetal hemoglobin

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About the article

Department of Medicine and Center for Sickle Cell Disease, Howard University College of Medicine, 2041 Georgia Avenue, Washington, DC20060, USA

Received: 2017-04-10

Revised: 2017-07-26

Accepted: 2017-08-01

Published Online: 2017-10-01

Published in Print: 2017-10-01

Ethical issues: Written informed consent was required of all enrolled subjects after protocol approval by the Institutional Review Board at the National Institutes of Health. The study was registered with Clinicaltrials.gov (identifier NCT01441141).

Conflict of interest:The authors report no conflicts of interest.

Author contributions:Conceived and designed study: DSD, CS, GRW, IB, JGT. QST and research coordination: KV, CS, KC, AC. Statistical analysis: KV, MQ, MAW, JGT. Data interpretation: DSD, KV, CS, KC, MQ, AC, LD, ANS, JAH, MAW, GRW, IB, JGT. Logistical support and QST training: AC, LD, GRW, ANS, JAH, IB. Drafted manuscript: JGT with contributions from DSD and KV. All authors contributed to manuscript writing and editing.

Citation Information: Scandinavian Journal of Pain, Volume 17, Issue 1, Pages 279–286, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1016/j.sjpain.2017.08.001.

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