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This study examined the role of central sensitization in the experience of pain among adolescents and young adults with the most severe genotypes of sickle cell disease (SCD). We hypothesized that adolescents and young adults with chronic SCD pain would demonstrate a higher perceptual response to repeated stimulation of identical intensity (i.e., temporal summation of pain, TSP) compared to counterparts with infrequent pain. We also examined psychological risk factors that can impact pain sensitivity.