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Modulation of pain in pediatric sickle cell disease: understanding the balance between endothelin mediated

Terika P Smith1, Alyssa M Schlenz2, Jeffrey C Schatz2

  • 1Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, USA.

Blood Cells, Molecules & Diseases
|December 10, 2014
PubMed

Insights

In children with sickle cell disease (SCD), an imbalance between vaso-dilatory apelin and vaso-constrictive endothelin-1 may worsen pain and vaso-occlusive episodes (VOEs). This ratio could indicate pain sensitization in SCD.

Area of Science:

  • Pediatric Hematology
  • Vascular Biology
  • Pain Medicine

Background:

  • Children with sickle cell disease (SCD) experience recurrent painful vaso-occlusive episodes (VOEs).
  • Vaso-constrictive and vaso-dilatory molecules are implicated in VOEs, with Endothelin-1 (ET-1) as a vasoconstrictor and apelin as a vasodilator.
  • The relationship between these molecules and pain in pediatric SCD is not fully understood.

Purpose of the Study:

  • To investigate the hypothesis that the ratio of vaso-dilatory to vaso-constrictive tone serves as a marker for pain sensitization and vaso-occlusion in children with SCD.
  • To explore the correlation between plasma levels of apelin and ET-1 and pain experiences in pediatric SCD.

Main Methods:

  • Measured plasma endothelin and apelin levels in 47 children with SCD.
  • Assessed procedural and baseline pain using child/caregiver reports and observational distress.
  • Evaluated pain history via retrospective chart review.

Main Results:

  • Plasma apelin levels decreased with age in children with SCD.
  • The apelin/ET-1 ratio negatively correlated with observational baseline pain.
  • The apelin/Big ET ratio correlated negatively with caregiver-rated baseline pain and positively with VOE history, potentially influenced by hydroxyurea treatment.

Conclusions:

  • An imbalance in the apelin and endothelin systems may contribute to increased VOEs and baseline pain in children with SCD.
  • The apelin/ET-1 ratio shows potential as a biomarker for pain and vaso-occlusion in pediatric SCD.
  • Further research is warranted to elucidate the therapeutic implications of modulating these vasoactive systems.

Keywords:
ApelinEndothelinPainSickle cell diseaseVaso-occlusive episodes

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