Acute pain model. This diagram shows proposed interactions between pathophysiologic mechanisms in sickle cell disease that lead to acute painful episodes. Key to mechanisms: green: balancing feedback loops, red: erythrocytes, orange: hemolysis, light blue: inflammation and oxidant stress, dark blue: ischemia and reperfusion, lavender: vasomotor, brown: coagulation, gray: angiogenesis, and light gray: pain modifiers. See text for details.