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Among <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> patients, vaso\u2010occlusive pain episodes vary in frequency and severity. Some patients rarely have painful crises, while others are admitted to the hospital multiple times in a year for parenteral analgesics. Opioids are the mainstay of therapy for <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>\u2010related pain. However, a subset of patients report continued pain despite escalating doses of opioids. Tolerance and opioid\u2010induced hyperalgesia (<jats:styled-content style=\"fixed-case\">OIH<\/jats:styled-content>) have been considered as possible explanations for this phenomenon. The activation of the <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate (<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>) receptor has been implicated in both tolerance and <jats:styled-content style=\"fixed-case\">OIH<\/jats:styled-content>. As a <jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content> receptor agonist, ketamine has been shown to modulate opioid tolerance and <jats:styled-content style=\"fixed-case\">OIH<\/jats:styled-content> in animal models and clinical settings. Low\u2010dose ketamine, by virtue of its <jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content> receptor agonist activity, could be a useful adjuvant to opioid therapy in patients with refractory <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>\u2010related pain. Based on limited studies of adjuvant ketamine use for pain management, low\u2010dose ketamine continuous infusion appears safe. Further clinical investigations are warranted to fully support the use of low\u2010dose ketamine infusion in patients with <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>\u2010related pain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pan.12172","type":"journal-article","created":{"date-parts":[[2013,4,9]],"date-time":"2013-04-09T11:19:32Z","timestamp":1365506372000},"page":"684-689","source":"Crossref","is-referenced-by-count":32,"title":["Low\u2010dose ketamine as a potential adjuvant therapy for painful vaso\u2010occlusive crises in sickle cell disease"],"prefix":"10.1111","volume":"23","author":[{"given":"Caitlin M.","family":"Neri","sequence":"first","affiliation":[{"name":"Children's National Medical Center Center for Cancer and Blood Disorders Washington DC USA"},{"name":"Department of Pediatrics School of Medicine The George Washington University Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie 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