Nociceptive and Neuropathic Pain Descriptors in Adults with Sickle Cell Disease are Associated with Overlap Activity in the Default, Salience and Somatosensory Networks

Central sensitization plays a crucial role in chronic pain experienced by individuals with sickle cell disease, yet current pain assessment tools fail to capture the complex, multidimensional nature of this pain. Disrupted neural communication serves as a key marker of central sensitization. Thus, this study investigated whether Painimation, a novel electronic visualization tool for pain assessment, correlates with functional connectivity in brain networks using enhanced resolution 7-Tesla imaging, potentially offering a simpler method to identify CS in patients with SCD. Using 7-Tesla magnetic resonance imaging, resting-state functional connectivity was examined in the default mode, salience, and somatosensory networks in 27 patients with SCD compared to 30 pain-free controls. Patients used Painimation to select visual animations representing their pain qualities and assigned intensity values. The most selected pain descriptors were throbbing, cramping, stabbing, and shooting pain. Patients with sickle cell disease demonstrated significantly decreased connectivity in all three networks when compared to controls, particularly between prefrontal regions in the default mode network, between the insula and paracentral regions in the salience network. The Painimation data showed that specific pain descriptors had distinct connectivity patterns, with cramping and stabbing pain exhibiting the strongest correlations within the somatosensory network. Notably, higher pain intensity scores for cramping and stabbing pain were associated with decreased functional connectivity in key somatosensory network regions. Linking Painimation descriptions with neuroimaging findings advances the understanding of pain processing mechanisms in sickle cell disease. PERSPECTIVE: This study provides novel insights into the neural correlations of subjective pain experiences in SCD, revealing how specific pain qualities relate to distinct patterns of brain connectivity. Identifying brain biomarkers that link pain descriptions, experiences and perception could transform the way pain is understood and managed in SCD.