title: Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use.
abstract: Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: (i) SCD baseline and controls, and (ii) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean ± standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32·4 ± 11·6 vs. 22·9 ± 7·6, P = 0·0009). SP in SCD pain was higher than baseline (78·1 ± 43·4 vs. 32·4 ± 11·6, P = 0·004). Haemolysis correlated with increased SP: Hb (r = -0·7, P = 0·0002), reticulocyte count (r = 0·61, P = 0·0016), bilirubin (r = 0·68, P = 0·0216), lactate dehydrogenase (r = 0·62, P = 0·0332), aspartate aminotransferase (r = 0·68, P = 0·003). Patients taking hydroxycarbamide had increased SP (β = 29·2, P = 0·007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment.
authors.affiliation: Section of Pediatric Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. abrandow@mcw.edu.|Medical College of Wisconsin, Milwaukee, WI, USA. abrandow@mcw.edu.|Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI, USA. abrandow@mcw.edu.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Brandow
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Wandersee
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.|Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI, USA.|Section of Quantitative Health Sciences, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Mahua
authors.initials: M
authors.lastname: Dasgupta
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.|Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI, USA.|Section of Quantitative Health Sciences, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Hoffmann
authors.affiliation: Section of Pediatric Hematology/Oncology at University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hillery
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.|Section of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Stucky
authors.affiliation: Section of Pediatric Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.|Medical College of Wisconsin, Milwaukee, WI, USA.|Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Panepinto
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D000986:Antisickling Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D012307:Risk Factors; D013373:Substance P / Q000097:blood*; D055815:Young Adult
chemical_list: D000986:Antisickling Agents; D015415:Biomarkers; D013373:Substance P; D006918:Hydroxyurea
keywords: haemolysis; pain; sensitization; sickle cell disease; substance P