Patient description: The patient is a 34-year-old African American man with the known history of Sickle cell disease comes to the clinic with severe bone pain. The patient had severe pain in his lower back that radiated to both thighs scored 9 out of 10. The patient has had positive history of sickle cell crises since childhood. He also had the same symptoms in past two weeks treated with oxycodone which was not beneficial to his pain. His PCP sent him to the emergency department to receive intra venous pain modulators. The patient is afebrile within the normal blood pressure. No splenomegaly was detected in the physical exam. He has no positive history of drug allergy. He won't smoke or uses any illicit drugs. The lab study is as bellow: Hgb: 8 g/dl WBC: 10000 /mm3 Plt: 300000 /ml MCV: 106 fL Hemoglobine electrophoresis: 91% HbS 6%HbF 3%HbA2 AST: 22 U/L ALT: 43 U/L Alk P: 53 U/L Ferritin: 1200 ng/ml

Clinical trial eligibility criteria: eligible ages (years): 6.0-21.0,  Sickle Cell Disease for Subjects with Sickle Cell Disease in Pain Crisis: 1. Age 6 to 21 years old. 2. Diagnosis of sickle cell anemia: a. Diagnosis of sickle cell disease (electrophoresis or HPLC documentation of hemoglobin SS, SC, S-beta-thalassemia or other hemoglobinopathies causing sickle cell disease is required). 3. Acute onset pain crisis in a distribution typical for that subject, onset within the last 7 days and for which hospitalization and parenteral narcotic pain treatment are required. 4. Ability to provide informed written consent  for Subjects with Sickle Cell Disease in Pain Crisis: 1. Pregnancy. 2. History of non-trivial injury, burns, surgery or skin ulcers on the arms. 3. Fever or suspected sepsis at time of pain crisis 4. Administration of any of the following drugs within the last 14 days Phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil) Endothelin-1 receptor blockers (bosentan, sitaxentan, ambrisentan, tezosentan) Nitric oxide donors (nitroglycerin, nitroprusside, nitrates) 5. Ingestion of caffeine within the 12 hours before the start of the study appointment, or tobacco use within the 30 days before the study appointment. 6. Diagnosis with any of the following chronic diseases or conditions History of high blood pressure History of high cholesterol History of diabetes History of chronic kidney disease (serum creatinine must not be greater than 2 mg/dL) History of coronary artery disease or peripheral vascular disease 7. Received a blood transfusion within 7 days of the study procedure. for Subjects with Sickle Cell Disease in Steady State: 1. Age 6-21 years 2. Diagnosis of sickle cell disease (electrophoresis or HPLC documentation of hemoglobin SS, SC, S-beta-thalassemia or other hemoglobinopathies causing sickle cell disease is required). 3. Ability to provide informed written consent for Subjects with Sickle Cell Disease in Steady State: 1. Pregnancy. 2. History of non-trivial trauma, burns, surgery or skin ulcers on the arms. 3. Fever or suspected sepsis at time of pain crisis 4. Experience of an acute pain crisis requiring intravenous (IV) narcotics and hospital admission within the last 14 days. 5. Ingestion of caffeine within the 12 hours before the start of the study appointment, or tobacco use within the 30 days before the study appointment. 6. Administration of any of the following drugs within the last 14 days