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Chronic elevation of the pain neurotransmitter substance P (<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>) sensitizes pain nociceptors. We evaluated<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>levels in controls and<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>patients during baseline and acute pain and investigated associations between<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>levels were measured using enzyme\u2010linked immunosorbent assay. Independent samples<jats:italic>t<\/jats:italic>\u2010test compared<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>levels between: (i)<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>baseline and controls, and (ii)<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>baseline and acute pain. Multivariate linear regression determined associations between<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>and haemolysis. We enrolled 35 African American controls, 25<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>baseline and 12<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>pain patients.<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>patients were 7\u201019\u00a0years old. Mean\u00a0\u00b1\u00a0standard deviation<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>level (pg\/ml) in<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>baseline was higher than controls (32\u00b74\u00a0\u00b1\u00a011\u00b76 vs. 22\u00b79\u00a0\u00b1\u00a07\u00b76,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b70009).<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>in<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>pain was higher than baseline (78\u00b71\u00a0\u00b1\u00a043\u00b74 vs. 32\u00b74\u00a0\u00b1\u00a011\u00b76,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b7004). Haemolysis correlated with increased<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>: Hb (<jats:italic>r\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>\u22120\u00b77,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b70002), reticulocyte count (<jats:italic>r\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b761,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b70016), bilirubin (<jats:italic>r\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b768,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b70216), lactate dehydrogenase (<jats:italic>r\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b762,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b70332), aspartate aminotransferase (<jats:italic>r\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b768,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b7003). Patients taking hydroxycarbamide had increased<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>(<jats:italic>\u03b2<\/jats:italic>\u00a0=\u00a029\u00b72,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0\u00b7007).<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>could be a mediator of or marker for pain sensitization in<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>and a biomarker and\/or target for novel pain treatment.<\/jats:p>","DOI":"10.1111\/bjh.14300","type":"journal-article","created":{"date-parts":[[2016,8,19]],"date-time":"2016-08-19T06:46:36Z","timestamp":1471589196000},"page":"237-245","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use"],"prefix":"10.1111","volume":"175","author":[{"given":"Amanda 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