title: Pathophysiology and principles of management of the many faces of the acute vaso-occlusive crisis in patients with sickle cell disease.
abstract: Effective management of sickle cell pain entails a thorough understanding of its pathophysiology and the pharmacogenomics of the opioids used to manage it. In recent years, there has been significant progress along these two lines. At the pathophysiologic level, there is evidence that the severity and frequency of painful stimuli modulate their transmission at the level of the dorsal horn of the spinal cord. This modulation is achieved via two channels: the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors. Initially, the AMPA channel controls the transmission of stimuli of mild-moderate severity. Once the AMPA channel reaches its limit of membrane depolarization, the NMDA channel is activated and facilitates the transmission of painful stimuli in a progressive fashion leading to central sensitization and glial activation. At the level of pharmacogenomics, the metabolism of each opioid is patient-specific. Glucuronidation is unique for the metabolism of morphine, hydromorphone, and oxymorphone. The metabolism of all other opioids requires specific Cytochrome P450 (CYP) isoenzymes. The activity of each isoenzyme and the activity of the metabolites of each opioid vary among patients depending on their genetic makeup and coexistent environmental factors such as the use of other medications that may enhance or inhibit the CYP isoenzyme activity.
authors.affiliation: Cardeza Foundation for Hematologic Research, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Ballas
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D000755:Anemia, Sickle Cell / Q000503:physiopathology*; D006801:Humans; D010146:Pain / Q000188:drug therapy*; D010597:Pharmacogenetics
chemical_list: D000701:Analgesics, Opioid
keywords: N-methyl-d-aspartic acid receptor; central sensitization; glial activation; pain; pharmacogenomics; sickle cell anemia; sickle cell disease; sodium channels; vaso-occlusive crisis