Genetics influence pain perception. For example, polymorphism rs4680 in the gene that encodes catechol-O-methyltransferase (COMT) results in the substitution of a methionine for the valine (wild type) at amino acid position 158, leading to a 3-4 fold reduction in COMT activity. Individuals homozygous for methionine at 158 have been shown to have greater pain perception and reduced endogenous opioid activity. COMT polymorphism rs4818 is a synonymous substitution, meaning that it does not alter the protein sequence. Even though the amino acid sequence is unchanged, synonymous mutations can alter the phenotype through effects on DNA transcription, mRNA structure, and gene splicing. COMT polymorphism rs4818 has been shown to affect opioid consumption in patients with acute pain.
Dr. Keith A. Candiotti, Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami School of Medicine, Miami, Florida, and colleagues examined the association between COMT rs4680 and rs4818 polymorphisms and opioid consumption in the acute postoperative period of patients after undergoing laparoscopic or open nephrectomy. The results of this study are discussed in the article titled “Catechol-O-Methyltransferase Polymorphisms Predict Opioid Consumption in Postoperative Pain,” which was published in this month’s issue of Anesthesia & Analgesia.
The authors studied 152 patients who met inclusion criteria between July 2005 and January 2013. Blood samples for COMT analysis were obtained 1 hour before surgery. For COMT rs4680, 61 subjects were Met/Met homozygotes, 60 were Val/Met, and 31 were Val/Val homozygotes. For COMT rs4848, 63 subjects were CC homozygotes, 68 were CG, and 21 were GG homozygotes. The allele frequencies for samples are in Hardy-Weinberg equilibration.
Patients who were Val/Val homozygous for rs 4680 had a significantly higher (36%) 24-hour opioid consumption compared with Met/Met homozygotes, even when adjusting for age, sex, ethnicity, BMI, smoking, and surgical approach. Polymorphism rs 4680 genotype did not affect 24-hour postoperative pain scores or requirements for PONV treatment.
Similarly, COMT polymorphism rs4818 did not affect 24-hour opioid consumption. However, patients with the CC genotype at polymorphism rs4818 required more antiemetic drugs than patients with the GG genotype.
Pain perception is a complex interplay between stimulus, treatment, environment, and psychological factors. Drs. Pamela Flood and David Clark, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, California, note in their accompanying editorial “Genetic Variability in the Activity of Monoamines: A Window into the Complexity of Pain,” “Future studies on catecholaminergic modulation of pain might best include complete genotyping of the 4 SNPs that have been found to relate to enzyme activity. In addition, they should include in their analysis gender and psychological variables that are known to be influenced by COMT genotype. To properly assess these variables, a careful multivariable analysis will be required that is powered to allow consideration of these factors. Finally, there is a growing expectation that nonexploratory reports include replication datasets to confirm or refute the findings of the primary analyses.”
This is one of two manuscripts on COMT genotype and pain perception in this issue. The other, on the relationship between COMT and chronic pain will be discussed in the next post.