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Altered Functional Connectivity in Sickle Cell Disease Exists at Rest and During Acute Pain Challenge

Zempsky, William T. MD, MPH*,†; Stevens, Michael C. PhD‡,§; Santanelli, James P. MPH*; Gaynor, Alexandra M. BS; Khadka, Sabin MS

doi: 10.1097/AJP.0000000000000492
Original Articles

Objectives: Sickle cell disease (SCD) is a chronic pain disorder in which abnormally shaped red blood cells obstruct microcirculation causing ischemia and pain. The lack of SCD responsiveness to analgesics has led many to propose that nociceptive neural systems engaged when detecting pain become sensitized, resulting in an enhancement of pain response.

Methods: Individuals with SCD and non-SCD controls were exposed to a painful stimuli of varying intensity using a pressure algometer and underwent several neuroimaging tasks.

Results: This study identified and characterized the neural correlates of possible central sensitization in SCD. We found functional connectivity abnormalities in individuals with SCD in the brain’s somatosensory network, salience network, and default mode network during both an unstructured resting state and paradigm involving acute pain challenge.

Discussion: There was evidence for both increased and decreased connectivity which is consistent with findings in other chronic pain disorders. Preliminary evidence was found that subcortical brain regions might contribute to neurodevelopmental abnormalities in chronic pain. The results support a model in which SCD pain sensitization involves abnormally low functional integration of brain regions that make use of nociceptive information to plan movements, and hyperconnectivity of various frontal and parietal lobe regions that direct attention to or represent higher-order abstractions within circuits involved with either nocioceptive processing or detection of abnormally salient environmental stimuli.

Supplemental Digital Content is available in the text.

*Division of Pain and Palliative Medicine, Connecticut Children’s Medical Center

Olin Neuropsychiatry Research Center, Institute of Living, Washington Street, Hartford

Department of Pediatrics, University of Connecticut School of Medicine, Farmington Avenue, Farmington

§Department of Psychiatry, Yale University School of Medicine, New Haven, CT

Supported by the Patrick and Catherine Weldon Donaghue Foundation West Hartford, CT. The authors declare no conflict of interest.

Reprints: William T. Zempsky, MD, MPH, 282 Washington Street, Hartford, CT 06106 (e-mail: wzempsk@connecticutchildrens.org).

Received August 19, 2016

Received in revised form November 28, 2016

Accepted February 8, 2017

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