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

Abstract

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.

Assessing neuropathic pain in sickle cell disease: How useful is quantitative sensory testing?

“…In this study, those who used hydroxyurea and strong opioids were more sensitive to HDT and PPT at the thenar eminence, respectively. This is the opposite to previous findings where SCD subjects on hydroxyurea had higher heat and mechanical pain thresholds compared to SCD subjects not on hydroxyurea (19), but similar to findings that chronic opioid therapy is associated with central sensitization in SCD (20). Higher acute pain scores were associated with being more sensitive to PPT at both the thenar eminence and dorsolateral foot.…”

Management of refractory chronic pain in sickle cell disease with intrathecal drug delivery system

“…The fight against pain in SCD is studied on several approaches, including drugs already in use in the clinical routine such as Hydroxyurea, Pregabalin, Ketamine, as well as biological ones with blood transfusion and the development of new drugs such as crizanlizumab and of L-Glutamine. 14 , 15 , 16 , 17 , 18 , 19 , 20 In a double-blind, placebo-controlled study, crizanlizumab (humanized anti-P-selectin monoclonal antibody) showed promise as a medication to prevent VOC, although it did not show a reduction in the rate of hospitalization days. 18 , 19 In November 2019, this drug received FDA approval in the USA, being indicated to reduce the frequency of VOC in individuals aged ≥ 16 years and diagnosed with SCD.…”

Severe Pain Profiles and Associated Sociodemographic and Clinical Characteristics in Individuals With Sickle Cell Disease

“…[11][12][13] For example, the use of hydroxyurea has been associated with lower occurrence of VOE pain compared with those not taking the medication. 14 However, little is known about the impact of treatments, such as hydroxyurea, on the occurrence of persistent or chronic pain over time.…”

“…Advances in treatments of SCD have shown to improve survival rates, manage disease complications, and prevent the occurrence of acute painful events 11–13. For example, the use of hydroxyurea has been associated with lower occurrence of VOE pain compared with those not taking the medication 14. However, little is known about the impact of treatments, such as hydroxyurea, on the occurrence of persistent or chronic pain over time.…”