Project Summary:
Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by severe acute pain. Red blood cell sickling leads to acute painful vaso-occlusive episodes (VOEs), triggering ischemia reperfusion, intravascular hemolysis, organ inflammation, and can cause premature death. Beyond acute VOE pain, patients also frequently live with chronic debilitating pain. This makes SCD pain particularly difficult to manage, as pain experienced by patients can be acute, chronic, or acute-on-chronic. Approximately 1,000 children, adolescents, and adults in Wisconsin live with SCD, a large proportion of whom reside in Milwaukee. In the U.S., SCD primarily affects Black individuals who are more likely to experience healthcare disparities, including low socioeconomic status and racial discrimination, both of which are barriers to seeking and accessing healthcare. Because the mainstay of pain treatment for SCD is opioid therapy, this further impedes patient access to care since opioid use among racial and ethnic minorities is stigmatized by some healthcare providers, resulting in undertreatment. Other treatments for patients with SCD, including over the counter NSAIDs and hydroxyurea, do not effectively treat pain, and are accompanied by side effects. Additionally, although gene therapy has strong potential for treating SCD, treatments are cost-prohibitive and have unknown long-term effects. Thus, effective, accessible analgesic treatments are pivotal for pain relief and improved quality of life for underrepresented individuals living with SCD in inner-city Milwaukee, the state of Wisconsin, and beyond.
This project will examine whether targeting hippocampal neuronal plasticity and inflammation attenuates cognitive deficits so prevalent in SCD.