DOI

https://doi.org/10.25772/YWF6-5H51

Author ORCID Identifier

0000-0003-2076-8319

Defense Date

2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

First Advisor

Wally Smith, MD

Second Advisor

Jennifer Jordan, PhD

Third Advisor

Dean Krusienski, PhD

Fourth Advisor

Dianne Pawluk, PhD

Fifth Advisor

Cecilia Valrie, PhD

Abstract

Pain is a hallmark of Sickle Cell Disease (SCD), a genetic hemoglobinopathy characterized by chronic hemolytic anemia, vaso-occlusion, and organ damage. While acute vaso-occlusive crises (VOC) have been extensively studied, the mechanisms underlying chronic pain and its interplay with brain function remain unclear. This dissertation investigates the relationships between cerebral blood flow (CBF), fluid cognition, and pain sensitivity in adults with SCD, utilizing advanced imaging techniques and validated assessment tools.

Arterial spin labeling (ASL) and functional magnetic resonance imaging (fMRI) were employed to measure CBF and brain activity, respectively. Pain sensitivity was assessed using the Pain Sensitivity Questionnaire (PSQ), and fluid cognition was evaluated through the NIH Toolbox. An exploratory mediation model was developed to investigate the role of altered cerebral hemodynamics and cognitive function in shaping pain cognition.

Key findings revealed significant disruptions in brain hemodynamics and reduced cognitive performance in SCD patients compared to healthy controls. Elevated regional CBF was associated with lower cognitive flexibility and slower processing speed, while heightened pain sensitivity correlated with altered brain activity in regions implicated in pain modulation and interoception. These findings suggest that chronic cerebral ischemia and neuroplastic changes may contribute to central sensitization and pain amplification in SCD, though further studies with larger samples are needed to confirm these associations..

This study provides novel insights into the neural mechanisms underlying pain cognition in SCD, highlighting the complex interplay between ischemia-induced brain alterations, cognitive dysfunction, and chronic pain. The findings underscore the need for targeted interventions to address both the physiological and cognitive dimensions of pain in SCD, offering a foundation for improved pain management strategies and quality of life for affected individuals.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-9-2025

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