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It is essential to differentiate between VOC\u2010associated pain and chronic pain, hyperalgesia, neuropathy, and neuropathic pain. The pathophysiology of VOCs includes polymerization of abnormal sickle hemoglobin, inflammation, and adhesion. Hydroxyurea, L\u2010glutamine, crizanlizumab, and voxelotor have been approved by the US Food and Drug Administration for reducing the frequency of VOCs; the European Medicines Agency has approved only hydroxyurea. Other novel treatments are in late\u2010stage clinical development in both the United States and the European Union. The development of agents for prevention and treatment of VOCs should be driven by our understanding of its pathophysiology.<\/jats:p>","DOI":"10.1111\/ejh.13430","type":"journal-article","created":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T01:46:30Z","timestamp":1587087990000},"page":"237-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":214,"title":["The vaso\u2010occlusive pain crisis in sickle cell disease: Definition, pathophysiology, and management"],"prefix":"10.1111","volume":"105","author":[{"given":"Deepika S.","family":"Darbari","sequence":"first","affiliation":[{"name":"Division of Hematology Children\u2019s National Medical Center Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien A.","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology Baylor College of Medicine Houston TX 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