Deepika S Darbari1, Kathleen J Vaughan2, Katherine Roskom2, Cassie Seamon2, Lena Diaw2, Meghan Quinn2, Anna Conrey2, Alan N Schechter3, Jennifer A Haythornthwaite4, Myron A Waclawiw5, Gwenyth R Wallen6, Inna Belfer7, James G Taylor8. 1. 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. 2. Genomic Medicine Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 3. Molecular Biology and Genetics Section, Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. 4. Center for Mind-Body Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA. 5. Office of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 6. National Institutes of Health, Clinical Center, Bethesda, MD, USA. 7. 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. 8. 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. Electronic address: James.taylor2@howard.edu.
Abstract
BACKGROUND AND AIMS: 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 512mN) 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.
BACKGROUND AND AIMS: 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 512mN) 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.
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