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Pathobiology and Novel Therapeutic Approaches for Pain in Sickle Cell Disease

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Key Personnel

  • Luis Almeida MD, PhD
  • Alfia Khaibullina PhD
  • Sayuri Kamimura, MS
  • Li Wang, MD, PhD
  • Julia Finkel, MD
  • Zenaide Quezado, MD

The spectrum of pain phenotypes in sickle cell disease (SCD) patients is highly variable.  A small percentage of SCD patients experience many vaso-occlusive crises per year: Five percent of patients account for over 30 percentof pain episodes, while 39 percent report few episodes of severe pain. Clearly, a better understanding of the pathobiology of SCD is needed to improve its therapy. Humanized sickle cell mice recapitulate several phenotypes of SCD patients and provide a model for the study of SCD pain. In a large cross-sectional study of SCD mice, we examined thermosensory response and sensory nerve fiber function using sine-wave electrical stimulation at 2000, 250, and 5Hz to preferentially stimulate Aβ, Aδ, and C sensory nerve fibers respectively. We used two strains of humanized SCD mice (BERKs and Townes) including one (Townes) with previously undescribed pain phenotype. These animals have been studied extensively and shown to display the hematologic abnormalities seen in SCD. We are now investigating the role of novel approaches to treat pain in SCD. Specifically we are examining the roles of the mTOR inhibitor rapamycin, which in erythroid precursor cells from normal human subjects has been shown to increase fetal hemoglobin. We are also evaluating the effect of an α2 adrenoreceptor agonist, dexmedetomidine in the nociception phenotype in animals with SCD.