Functional MRI BOLD response in sickle mice with hyperalgesia

Patients with sickle cell anemia (SCA) have abnormal hemoglobin (sickle hemoglobin S) leading to the crystallization of hemoglobin chains in red blood cells (RBCs), which assume sickle shape and display reduced flexibility. Sickle RBCs (sRBCs) adhere to vessel walls and block blood flow, thus preventing oxygen delivery to the tissues leading to vaso-occlusive crises (VOC), acute pain and organ damage. SCA patients often have chronic pain that can be attributed to inflammation, vasculopathy, neuropathy, ischemia-reperfusion injury and organ damage. Blood oxygenation level-dependent (BOLD) based functional magnetic resonance imaging (fMRI) technique that is commonly used for noninvasively mapping spontaneous or evoked brain activation in human or animal models has been applied in this study to assess abnormal oxygenation change in the brains of mice with SCA in response to hypoxia. We found that hyperalgesic HbSS-BERK sickle mice with chronic pain display reduced BOLD response to a hypoxia challenge compared to their control HbAA-BERK mice. Hypoxia/reoxygenation (H/R) treated sickle mice under acute pain episode exhibit even smaller BOLD signal changes than sickle mice without H/R, suggestive of correlations between cerebral BOLD signal changes and nociception.