Children with sickle cell disease (SCD) have painful vaso-occlusive episodes 
(VOEs), which often reoccur across the individual's lifespan. Vaso-constrictive 
and vaso-dilatory molecules have been hypothesized to play a role in VOEs. 
Endothelin-1 (ET-1) is a potent vasoconstrictor that is released during VOEs and 
is correlated with pain history. Apelin is a vaso-dilatory peptide that also has 
a modulatory role in pain processing. We hypothesize that the ratio between 
vaso-dilatory and vaso-constrictive tone in children with SCD may be a marker of 
pain sensitization and vaso-occlusion. Plasma endothelin and apelin levels were 
measured in 47 children with SCD. Procedural pain and baseline pain were 
assessed via child- and caregiver-reports and observational distress. Pain 
history was assessed using retrospective chart review. Plasma apelin was related 
to age, with decreased levels in older children. The ratio between apelin and 
ET-1 was negatively correlated to observational baseline pain. The ratio between 
apelin and Big ET was negatively correlated to caregiver ratings of baseline 
pain and positively correlated to history of VOEs, which is possibly due to 
hydroxyurea treatment. These results suggest that an imbalance in the apelin and 
endothelin systems may contribute to an increasing number of VOEs and baseline 
pain in children with SCD.