Preliminary evidence that hydroxyurea is associated with attenuated peripheral sensitization in adults with sickle cell disease

Introduction: Hydroxyurea (HU) is a drug that targets the underlying pathophysiology of sickle cell disease (SCD); however, it continues to be an underutilized treatment for adults. Previous research suggests that HU treatment can result in fewer hospital contacts for acute vaso-occlusive pain crises (VOC). Hydroxyurea's impact on non-VOC pain, however, is not well established. Objectives: This study examined whether HU moderated patterns of static and dynamic pain processing and clinical pain in SCD individuals. Methods: Fifty-eight patients with SCD (N taking HU = 17) underwent quantitative sensory testing (QST) and completed twice daily symptom diaries for 12 weeks. Quantitative sensory testing established thermal threshold and tolerance, mechanical thresholds, and thermal and mechanical temporal summation of pain. Results: Groups did not differ in age, sex, or opioid use. After controlling for morphine use, QST results showed that participants taking HU had higher heat and mechanical pain thresholds (static QST measures) but not thermal and mechanical temporal summation (dynamic QST measures). Participants taking HU also reported lower VOC pain compared with SCD participants not taking HU; however, HU did not moderate non-VOC clinical pain ratings. Conclusion: Findings cautiously suggest that HU acts on pain hypersensitivity and VOC pain, rather than inhibiting pain facilitation and non-VOC pain. These differences may reflect HU's influence on peripheral rather than central sensitization. Future research is warranted to replicate these findings in a larger sample and determine whether early HU administration can prevent peripheral sensitization in SCD individuals.