Distinct Brain Connectivity Patterns in Sickle Cell Disease: A Biomarker for Chronic Pain Severity

Background: Central nervous system complications are common in sickle cell disease (SCD), and the defining associated biomarkers are becoming increasingly relevant for physicians in diagnostic and prognostic contexts. Recent studies have reported altered brain connectivity in pain processing, highlighting a new avenue for developing sensitive measures of SCD severity. Method: This cross-sectional study used graph theory concepts to analyze effective connectivity in individuals with SCD and healthy controls during rest and motor imagery tasks. The SCD group was further divided into two subgroups based on pain intensity (less pain or more pain) during the evaluation. Results: Individuals with SCD and chronic pain exhibited a distinct brain connectivity signature compared to healthy individuals and within pain sublevels. Conclusion: Chronic pain in SCD shows a unique brain connectivity pattern when compared to healthy subjects and across different pain levels. The results support the hypothesis that chronic pain condition is associated with decreased interhub connections and increased intrahub connections for specific brain rhythms. Furthermore, the small-world parameter can distinguish SCD individuals from controls and differentiate pain levels within SCD individuals, offering a promising biomarker for clinical assessment.