CYP2D6 Pharmacogenetics Testing and Post-Cesarean Section Pain Scores-a Preliminary Study

Abstract

Objective: Prospective observational study to analyze CYP2D6 pharmacogenetics in 55 Portuguese adult parturients undergoing elective cesarean section and to investigate the association between CYP2D6 alleles and pain score.

Methods: DNA was extracted from peripheral blood by standard methods. Genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, and *41) and copy number determination with TaqMan probes by real-time polymerase chain reaction (PCR). Allele duplications were confirmed (long PCR and PCR-restriction fragment length polymorphism). Theoretical metabolic profiles prediction was based on genetic data and activity scores. Association was investigated between genotypes and predicted phenotypes with pain scores. Statistical analysis was performed by using a χ2 test, and significance was set at P < 0.05.

Results: The percentage of poor, intermediate, extensive, and ultrarapid metabolizers found were 9%, 38%, 46%, and 7%, respectively. The results reveal a positive association between alleles *4, *10, and pain.

Conclusions: A positive association was found between predicted reduced or null activity of CYP2D6 and increased pain. It can be hypothesized that if CYP2D6 activity is reduced, tyramine metabolism will decrease, resulting in reduced formation of endogenous dopamine. Consequently, activation of the signal transduction pathways that controls pain and analgesic effect may be reduced, leading to an increase in pain. Therefore, we would recommend CYP2D6 genotyping to anticipate the needs for analgesia, which will help to adjust opioid dose and maximize clinical efficacy while reducing side effects.

Keywords: CYP2D6; Cesarean Section; Dopamine; Modulation of Pain; Pain; Pharmacogenetics; Tyramine.