Thinking beyond sickling to better understand pain in sickle cell disease.

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Painful vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD); however, many patients experience frequent daily pain that does not follow the pattern of typical VOCs. This pain of variable severity, also referred as persistent pain in the SCD literature, contributes to significant morbidity and poor quality of life and often fails to respond adequately to standard SCD therapies. In this article, we briefly describe types of pain encountered in SCD with a special emphasis on persistent pain. We discuss altered pain processing as a potential contributing mechanism, which may lead to development and maintenance of persistent pain. We describe the advances in the non-SCD pain field that may help improve the understanding of SCD pain. We highlight the need for further investigation in this area because some of these patients with persistent pain may benefit from receiving adjuvant mechanism-based therapies used successfully in other non-SCD chronic pain conditions.