Sickle cell disease (SCD) is the most common monogenic disease worldwide. Currently, about 250 million people worldwide carry the gene responsible for the various types of sickle hemoglobinopathies. About 300,000 infants are born annually with SCD worldwide, although due to the lack of universal newborn screening in the most affected countries, this number is likely to underestimate the number of infants born with SCD. In the United States, about 1 in every 500 African Americans are born with the disease, and the affected population is expected to increase in the near future.1-3 The molecular lesion of the sickle hemoglobin (HbS) is a point mutation (GAG → GTG) in exon 1 of the β-globin gene, resulting in the substitution of glutamic acid by valine at position 6 of the β-globin polypeptide chain.4,5 This single point mutation renders the sickle gene pleiotropic in nature with multiple phenotypic expressions associated with complex genetic interactions and modifiers that are not well understood.4,5
Clinically, SCD is a tetrad of (1) pain syndromes, (2) anemia and its sequelae, (3) organ failure, and (4) comorbid conditions. Pain, however, is the major aspect of the disease, and the acute sickle cell painful vaso-occlusive crisis (VOC) is the hallmark of SCD in general and sickle cell anemia (SCA) in particular.6 VOCs are the most common cause of visits to the emergency department (ED) and/or hospital admissions of patients with SCD.7 Other types of pain secondary to SCD itself also occur. These include chronic pain syndromes, neuropathic pain, and pain between VOCs. The definition, incidence, frequency, severity, and distinctive features of these pain syndromes are highly controversial and have not been investigated in depth, and except for sporadic anecdotes, the current literature, to the best of our knowledge, is devoid of such reports.
Besides controversy, another major feature of VOCs is heterogeneity, usually latitudinally among patients and less often longitudinally in the same patient. Being aware of this vast heterogeneity will streamline management of affected individuals and avoid stereotyping and faulty accusations of aberrant behavior, as has been described previously.8
The purpose of this chapter is to describe the various types of acute and chronic sickle cell pain. This includes their pathophysiology, clinical picture, complications, management, and effect on quality of life.
SCD in general and SCA in particular are almost synonymous with pain, and the VOC is its hallmark. Vascular occlusion causes damage (microinfarcts) of the tissues supplied by the occluded vessel. This, in turn, involves interactions with vascular endothelium, as well as contributions from hemolysis, inflammation, and coagulation.9 Consequently, tissue damage generates a number of inflammatory mediators that initiate an electrical impulse of pain transmitted along peripheral nerves (Aδ and C fibers) to the ...