Genetic variants of COMT gene expression and influence on pain perception

Abstract

Introduction. Catechol-O-methyltransferase (COMT) is a pivotal enzyme responsible for deactivating biologically active catechols, including crucial neurotransmitters such as dopamine, norepinephrine, and adrenaline. These neurotransmitters significantly influence pain modulation, and variations in the gene encoding the COMT enzyme directly impact pain sensitivity. Aim of study. This study aims to comprehensively explore the genetic variants within the COMT gene and their consequential effects on pain perception. Methods and materials. Conducting a thorough literature review, this study utilized PubMed and ScienceDirect databases to investigate key terms like "genetic variants of the COMT enzyme", "COMT enzyme", "COMT gene", "genetic variants of COMT and pain", and "polymorphism of the catechol-o-aminotransferase gene". 147 sources were found, from which we selected 15. Results. Existing literature analysis reveals various types of COMT gene polymorphisms, with the most extensively studied being the single nucleotide type Rs4680 (Val158Met). This polymorphism substitutes valine for methionine at the 158 locus, leading to a significant reduction (three to four-fold) in COMT enzyme activity. Consequently, genotypes Val/Val, Val/Met, and Met/Met correspond to high, intermediate, and low levels of COMT enzyme activity. Lower COMT enzyme activity intensifies dopaminergic system activation, impacting the metabolism of catecholamines. Enhanced dopaminergic neurotransmission results in reduced enkephalin peptides, consequently heightening mu-opioid receptor regulation. Individuals with the Met/Met genotype exhibit increased regional density of mu-opioid receptors in the brain, correlated with heightened sensory and affective pain ratings. Conclusion. This literature review highlights how distinct expressions of the COMT gene influence pain perception. Understanding these mechanisms aids in comprehending the development of various pain disorders, offering potential ways for refining pain management strategies in human populations. deactivating biologically active catechols, including cruci al neurotransmitters such as dopamine, norepinephrine, and adrenaline. These neurotransmitters signi ficantly influence pain modulation, and variations in the gene encoding the COMT enzyme directly impact pain sensitivity. Aim of study. This study aims to comprehensively explore the genetic varian ts within the COMT gene and their consequential effects on pain perception. Methods and materials. Conducting a thorough literature review, this study utilized PubMe d and ScienceDirect databases to investigate key terms like "gene tic variants of the COMT enzyme", "COMT enzyme", "COMT gene", "genetic variants of COMT and pa in", and "polymorphism of the catechol-o-aminotransferase gene". 147 sources were fo und, from which we selected 15. Results. Existing literature analysis reveals various types of COMT gene polymorphisms, with the most extensively studied being the single nucleotide type Rs4680 ( Val158Met). This polymorphism substitutes valine for methionine at the 158 locus, leading to a significant reduction (three to four-fold) in COMT enzyme activity. Consequently, ge notypes Val/Val, Val/Met, and Met/Met correspond to high, intermediate, and low levels of COMT enzyme activity. Lower COMT enzyme activity intensifies dopaminergic system activ ation, impacting the metabolism of catecholamines. Enhanced dopaminergic neurotransmission re sults in reduced enkephalin peptides, consequently heightening mu-opioid receptor regulation . Individuals with the Met/Met genotype exhibit increased regional density of mu-opioid rece ptors in the brain, correlated with heightened sensory and affective pain ratings. Conclusion. This literature review highlights how distinct expressions of the COMT gene influence pain perception. Understanding these mechanisms a ids in comprehending the development of various pain disorders, offering potential w ays for refining pain management strategies in human populations.