The frequency of pain crises in patients with sickle cell disease is quite variable. Some patients never experience pain crises while others can have 3 or more crises per year. In the monoamine neurotransmitter systems, both catechol-O-methyltransferase (COMT) and dopamine D3 receptor (DRD3) genes have single nucleotide polymorphisms (SNP) that influence pain perception. The relationship between COMT polymorphisms and acute pain was described in yesterday’s post, “Catechol-O-methyltransferase polymorphisms, acute pain and PONV: a study of nephrectomy patients.” DRD3, one of 5 dopamine receptors that affect endogenous dopamine receptor activity, has been associated with higher thermal pain thresholds. Dr. Zaijie Jim Wang, Biopharmaceutical Sciences Department, University of Illinois at Chicago, Chicago, Illinois, and colleagues sought to determine how these polymorphisms among adult patients with sickle cell disease affected baseline pain and acute care utilization. Their results are published in this month’s issue of Anesthesia & Analgesia and summarized in the article titled “Dopamine D3 Receptor Ser9Gly and Catechol-O-methyltransferase Val158Met Polymorphisms and Acute Pain in Sickle Cell Disease.“
The authors studied 130 patients with sickle cell disease. For the DRD3 genotype, 42% were Gly/Gly, 50% were Gly/Ser, and 8% were Ser/Ser. For the COMT genotype, 45% were Val/Val or Val/Met, and 9% were Met/Met. Patients homozygous for Gly/Gly genotypes at the DRD3 gene were about 4.5 times more likely to need admission to an emergency department or acute care center than patients heterozygous at the locus. Patients with the COMT MET allele were more likely to need emergency department or acute care center admission, which would indicate they had more pain.
Other variants such as fetal hemoglobin and beta thalassemia are known to affect pain. These were not analyzed in the study. As indicated in yesterday’s post, psychological factors are affected by the COMT genotype, and these may contribute to differences in pain perception.
As Drs. Pamela Flood, and David Clark, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, California, write in the accompanying editorial titled “Genetic Variability in the Activity of Monoamines: A Window into the Complexity of Pain,” “Given the complex biology that underlies nociceptive transmission and pain manifestation, it is not surprising that the findings in studies of COMT genotype and pain manifestation are not straightforward. While there is ample scientific rational[e] to consider the relationship, particularly in chronic pain syndromes…it may be that we are looking at the wrong endpoint. While the effect of catecholamine concentration on pain transmission is variable, the relationship with psychological modulators such as anxiety, depression and catastrophizing may be better supported. Consider how this may have affected the current reports; perhaps sickle cell patients who express the 158Met form of COMT experienced similar nociceptive input, but were more motivated to seek treatment thus explaining the higher incidence of reported crises.”