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SCD patients report that VOC can be triggered by stress, cold exposure, and, pain itself. We anticipated that pain could cause neural\u2010mediated vasoconstriction, decreasing regional blood flow and promoting entrapment of sickle cells in the microvasculature. Therefore, we measured microvascular blood flow in the fingers of both hands using plethysmography and laser\u2010Doppler flowmetry while applying a series of painful thermal stimuli on the right forearm in 23 SCD patients and 25 controls. Heat pain applied to one arm caused bilateral decrease in microvascular perfusion. The vasoconstriction response started before administration of the thermal pain stimulus in all subjects, suggesting that pain anticipation also causes significant vasoconstriction. The time delay between thermal pain application and global vasoconstriction ranged from 5 to 15.5 seconds and increased with age (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01). Although subjective measures, pain threshold and pain tolerance were not different between SCD subjects and controls, but the vaso\u2010reactivity index characterizing the microvascular blood flow response to painful stimuli was significantly higher in SCD patients (<jats:italic>P<\/jats:italic>\u2009=\u2009.0028). This global vasoconstriction increases microvascular transit time, and may promote entrapment of sickle cells in the microvasculature, making vaso\u2010occlusion more likely. The rapidity of the global vasoconstriction response indicates a neural origin that may play a part in the transition from steady\u2010state to VOC, and may also contribute to the variability in VOC frequency observed in SCD patients.<\/jats:p>","DOI":"10.1002\/ajh.24858","type":"journal-article","created":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T00:22:47Z","timestamp":1499991767000},"page":"1137-1145","source":"Crossref","is-referenced-by-count":33,"title":["Individuals with sickle cell disease have a significantly greater vasoconstriction response to thermal pain than controls and have significant vasoconstriction in response to anticipation of pain"],"prefix":"10.1002","volume":"92","author":[{"given":"Maha","family":"Khaleel","sequence":"first","affiliation":[{"name":"Section of Hematology Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mammen","family":"Puliyel","sequence":"additional","affiliation":[{"name":"Section of Hematology Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Shah","sequence":"additional","affiliation":[{"name":"Section of Hematology Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sunwoo","sequence":"additional","affiliation":[{"name":"Biomedical engineering Viterbi School of Engineering Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta M.","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Pulmonology Children's Hospital Los Angeles, Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patjanaporn","family":"Chalacheva","sequence":"additional","affiliation":[{"name":"Biomedical engineering Viterbi School of Engineering Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwara","family":"Thuptimdang","sequence":"additional","affiliation":[{"name":"Biomedical engineering Viterbi School of Engineering Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Detterich","sequence":"additional","affiliation":[{"name":"Division of Cardiology Children's Hospital Los Angeles, Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Wood","sequence":"additional","affiliation":[{"name":"Biomedical engineering Viterbi School of Engineering Los Angeles California"},{"name":"Division of Cardiology Children's Hospital Los Angeles, Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie","family":"Tsao","sequence":"additional","affiliation":[{"name":"Pediatric Pain Program, University of California Los Angeles Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonnie","family":"Zeltzer","sequence":"additional","affiliation":[{"name":"Pediatric Pain Program, University of California Los Angeles Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sposto","sequence":"additional","affiliation":[{"name":"Section of Hematology Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Keck School of Medicine Los Angeles California"},{"name":"Department of Preventive Medicine, Keck School of Medicine University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C. 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