title: Modulation of pain in pediatric sickle cell disease: understanding the balance between endothelin mediated vasoconstriction and apelin mediated vasodilation.
abstract: 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.
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, USA. Electronic address: terika.smith@uscmed.sc.edu.
authors.forename: Terika P
authors.initials: TP
authors.lastname: Smith
authors.affiliation: Department of Psychology, University of South Carolina, Columbia, SC, USA.
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Schlenz
authors.affiliation: Department of Psychology, University of South Carolina, Columbia, SC, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Schatz
authors.affiliation: RTI International, Research Triangle Park, NC, USA.
authors.forename: Rangan
authors.initials: R
authors.lastname: Maitra
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, USA; Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Sweitzer
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D000986:Antisickling Agents / Q000627:therapeutic use; D000073861:Apelin; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D019332:Endothelin-1 / Q000097:blood / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D008297:Male; D010146:Pain / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D010147:Pain Measurement; D015398:Signal Transduction; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: C115436:APLN protein, human; D000986:Antisickling Agents; D000073861:Apelin; D015415:Biomarkers; D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; D006918:Hydroxyurea
keywords: Apelin; Endothelin; Pain; Sickle cell disease; Vaso-occlusive episodes