Sickle cell disease (SCD) is a genetic disease due to a single nucleotide mutation in the b-globin gene on chromosome 11, resulting in the substitution of valine for glutamate at the sixth amino acid [10]. The disease is characterized by hemoglobin polymerization, red cell sickling and hemolysis, and multiple complications. Recent advances in its treatment have significantly prolonged patients’ life expectancy, yet little progress has been made in understanding and treating the hallmark of the disease—pain, a lifelong companion of people living with SCD [1, 16]. In fact, pain and SCD are so intimately intertwined that African tribal words for the disease, spoken centuries before the first description of SCD by Dr. Herrick [7] in the Western literature, are onomatopoeic for pain.

Myths and misunderstanding exist for pain in SCD. Patients experience both acute pain crisis and chronic pain [18, 20]. The latter can be more severe than cancer pain or labor pain during childbirth [20]. To this day, it remains controversial whether there is a component of neuropathic pain in SCD, although accumulating evidence would suggest so [12, 13, 20]. Additional evidence came from animal studies in which transgenic mice exhibited long-lasting evoked hypersensitivity to mechanical, heat, and noxious cold stimuli [8, 11, 19].