Severe recurrent pain is the most common cause of acute morbidity in sickle cell disease1. The underlying pathogenesis was initially thought to be ischemia from obstruction of capillary beds by stiffened red blood cells; however, there is evidence that other factors contribute to the pathogenesis of sickle cell pain crisis, such as inflammation and coagulation, ischemia-reperfusion injury, angiogenesis balance, and vasomotor tone processes that are regulated by endothelial nitric oxide.