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      Association between COMT polymorphism, labor anxiety, and analgesia in pregnant women

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          COMT gene polymorphism is associated with mental disorders and sensitivity to pain. In this study, we investigated the association between the COMT gene polymorphism and labor anxiety and analgesia in pregnant women.

          Subjects and methods

          A total of 425 pregnant women undergoing labor analgesia were selected from May 2016 to February 2018. The COMT gene polymorphism was detected through the PCR with restriction fragment length polymorphism technique before childbirth. According to a COMT genotype, the enrolled pregnant women were subdivided into the Val/Val (allele GG) group, the Met/Met (allele AA) group, and the Val/Met (allele GA) group. Then, the intervertebral space of all pregnant women was injected with 3 mL of 2% lidocaine +6 mL of 0.08% ropivacaine and 6 µg of fentanyl. Labor analgesia was administered as follows: 80 mg of 0.08% ropivacaine +100 µg of fentanyl + normal saline to 100 mL. The general characteristics of the women were examined and recorded. In addition, the State Anxiety Inventory (SAI), VAS, Ramsay sedation score, and epinephrine and norepinephrine levels were compared and analyzed.


          A total of 391 pregnant women were enrolled in this study; among these pregnant women, there were 180 pregnant women in the GG group, 132 in the GA group, and 99 in the AA group. The minor allele frequency of COMT polymorphism among these pregnant women was 32.8%. Compared with the GG group, the SAI and VAS scores were higher, the Ramsay sedation score was lower, and the epinephrine and norepinephrine levels were higher in AA and GA groups ( P<0.05). Nonetheless, there was no statistically significant difference in the SAI, VAS, Ramsay sedation score, and epinephrine and norepinephrine levels between the groups AA and GA ( P>0.05).


          The COMT gene polymorphism was associated with labor anxiety and analgesia among pregnant women, and the Val158Met mutation in the COMT gene could lead to worse labor anxiety and less-effective labor analgesia in pregnant women.

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          Most cited references 25

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          Genetic basis for individual variations in pain perception and the development of a chronic pain condition.

          Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase (COMT) that we designated as low pain sensitivity (LPS), average pain sensitivity (APS) and high pain sensitivity (HPS). We show that these haplotypes encompass 96% of the human population, and five combinations of these haplotypes are strongly associated (P=0.0004) with variation in the sensitivity to experimental pain. The presence of even a single LPS haplotype diminishes, by as much as 2.3 times, the risk of developing myogenous temporomandibular joint disorder (TMD), a common musculoskeletal pain condition. The LPS haplotype produces much higher levels of COMT enzymatic activity when compared with the APS or HPS haplotypes. Inhibition of COMT in the rat results in a profound increase in pain sensitivity. Thus, COMT activity substantially influences pain sensitivity, and the three major haplotypes determine COMT activity in humans that inversely correlates with pain sensitivity and the risk of developing TMD.
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            COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor.

            Responses to pain and other stressors are regulated by interactions between multiple brain areas and neurochemical systems. We examined the influence of a common functional genetic polymorphism affecting the metabolism of catecholamines on the modulation of responses to sustained pain in humans. Individuals homozygous for the met158 allele of the catechol-O-methyltransferase (COMT) polymorphism (val158met) showed diminished regional mu-opioid system responses to pain compared with heterozygotes. These effects were accompanied by higher sensory and affective ratings of pain and a more negative internal affective state. Opposite effects were observed in val158 homozygotes. The COMT val158met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli.
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              Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis.

              Genetic variation in catechol-O-methyltransferase (COMT), encoding an enzyme critical for prefrontal dopamine flux, has been studied extensively using both behavioral and neuroimaging methods. In behavior, pleiotropic action of a functional Val(158)Met (rs4680) polymorphism on executive cognition and emotional stability has been described and proposed to be of evolutionary significance (the 'warrior/worrier' hypothesis). We conducted a meta-analysis of all available neuroimaging studies of rs4680 to investigate the evidence for a neural substrate of this behavioral pleiotropy. We show significant association between the COMT genotype and prefrontal activation, with large (d=0.73) effect size without evidence for publication bias. Strong and opposing effects were found for executive cognition paradigms (favoring Met allele carriers) and emotional paradigms (favoring Val), providing meta-analytical evidence for a neural substrate for the pleiotropic behavioral effects of COMT genetic variation and validating the use of intermediate phenotypes as a method to bridge between genes and behavior.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                27 February 2019
                : 12
                : 779-785
                [1 ]Department of Anesthesiology, Neijiang City Central Maternal and Child Health Care Hospital, Neijiang 641000, Sichuan, China
                [2 ]Department of Anesthesiology and Pain Management, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China, zhangying021210@ 123456163.com ; 15328408055@ 123456163.com
                [3 ]Department of Anesthesiology, Sichuan Provincial Armed Police Corps Hospital, Leshan 614000, Sichuan, China
                Author notes
                Correspondence: Ying Zhang; Qing Liu, Department of Anesthesiology and Pain Management, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Longmatan District, No. 182 Chunhui Road, Luzhou 646000, Sichuan, China, Email zhangying021210@ 123456163.com ; 15328408055@ 123456163.com
                © 2019 Ren et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Anesthesiology & Pain management

                labor analgesia, comt, labor anxiety, polymorphism


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