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      Single nucleotide polymorphisms associated with postoperative inadequate analgesia after single-port VATS in Chinese population

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          Abstract

          Background

          Postoperative inadequate analgesia following video-assisted thoracoscopic surgery (VATS) is a common and significant clinical problem. While genetic polymorphisms may play role in the variability of postoperative analgesia effect, few studies have evaluated the associations between genetic mutations and inadequate analgesia after single-port VATS.

          Methods

          Twenty-eight single nucleotide polymorphisms (SNPs) among 18 selected genes involved in pain perception and modulation were genotyped in 198 Chinese patients undergoing single-port VATS. The primary outcome was the occurrence of inadequate analgesia in the first night and morning after surgery which was defined by a comprehensive postoperative evaluation. Multivariable logistic regression analyses were used to identify the association between genetic variations and postoperative inadequate analgesia.

          Results

          The prevalence of postoperative inadequate analgesia was 45.5% in the present study. After controlling for age and education level, association with inadequate analgesia was observed in four SNPs among three genes encoding voltage-gated sodium channels. Patients with the minor allele of rs33985936 ( SCN11A), rs6795970 ( SCN10A), and 3312G > T ( SCN9A) have an increased risk of suffering from inadequate analgesia. While the patients carrying the minor allele of rs11709492 ( SCN11A) have lower risk experiencing inadequate analgesia.

          Conclusions

          We identified that SNPs in SCN9A, SCN10A, and SCN11A play a role in the postoperative inadequate analgesia after single-port VATS. Although future larger and long-term follow up studies are warranted to confirm our findings, the results of the current study may be utilized as predictors for forecasting postoperative analgesic effect for patients receiving this type of surgery.

          Trial registration

          This study was retrospectively registered in the ClinicalTrials.gov Registry ( NCT03916120) on April 16, 2019.

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          Most cited references36

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          The Role of Voltage-Gated Sodium Channels in Pain Signaling.

          Acute pain signaling has a key protective role and is highly evolutionarily conserved. Chronic pain, however, is maladaptive, occurring as a consequence of injury and disease, and is associated with sensitization of the somatosensory nervous system. Primary sensory neurons are involved in both of these processes, and the recent advances in understanding sensory transduction and human genetics are the focus of this review. Voltage-gated sodium channels (VGSCs) are important determinants of sensory neuron excitability: they are essential for the initial transduction of sensory stimuli, the electrogenesis of the action potential, and neurotransmitter release from sensory neuron terminals. Nav1.1, Nav1.6, Nav1.7, Nav1.8, and Nav1.9 are all expressed by adult sensory neurons. The biophysical characteristics of these channels, as well as their unique expression patterns within subtypes of sensory neurons, define their functional role in pain signaling. Changes in the expression of VGSCs, as well as posttranslational modifications, contribute to the sensitization of sensory neurons in chronic pain states. Furthermore, gene variants in Nav1.7, Nav1.8, and Nav1.9 have now been linked to human Mendelian pain disorders and more recently to common pain disorders such as small-fiber neuropathy. Chronic pain affects one in five of the general population. Given the poor efficacy of current analgesics, the selective expression of particular VGSCs in sensory neurons makes these attractive targets for drug discovery. The increasing availability of gene sequencing, combined with structural modeling and electrophysiological analysis of gene variants, also provides the opportunity to better target existing therapies in a personalized manner.
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            Genetic influence on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament.

            While a variety of cultural, psychological and physiological factors contribute to variability in both clinical and experimental contexts, the role of genetic factors in human pain sensitivity is increasingly recognized as an important element. This study was performed to evaluate genetic influences on variability in human pain sensitivity associated with gender, ethnicity and temperament. Pain sensitivity in response to experimental painful thermal and cold stimuli was measured with visual analogue scale ratings and temperament dimensions of personality were evaluated. Loci in the vanilloid receptor subtype 1 gene (TRPV1), delta opioid receptor subtype 1 gene (OPRD1) and catechol O-methyltransferase gene (COMT) were genotyped using 5' nuclease assays. A total of 500 normal participants (306 females and 194 males) were evaluated. The sample composition was 62.0% European American, 17.4% African American, 9.0% Asian American, and 8.6% Hispanic, and 3.0% individuals with mixed racial parentage. Female European Americans with the TRPV1 Val(585) Val allele and males with low harm avoidance showed longer cold withdrawal times based on the classification and regression tree (CART) analysis. CART identified gender, an OPRD1 polymorphism and temperament dimensions of personality as the primary determinants of heat pain sensitivity at 49 degrees C. Our observations demonstrate that gender, ethnicity and temperament contribute to individual variation in thermal and cold pain sensitivity by interactions with TRPV1 and OPRD1 single nucleotide polymorphisms.
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              Postthoracotomy pain management problems.

              Pain after thoracotomy is very severe, probably the most severe pain experienced after surgery. Thoracic epidural analgesia has greatly improved the pain experience and its consequences and has been considered the standard for pain management after thoracotomy. This view has been challenged recently by the use of paravertebral nerve blocks. Nevertheless, severe ipsilateral shoulder pain and the prevention of the postthoracotomy pain syndrome remain the most important challenges for management of postthoracotomy pain.
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                Author and article information

                Contributors
                zryanmin@zju.edu.cn
                Journal
                BMC Anesthesiol
                BMC Anesthesiol
                BMC Anesthesiology
                BioMed Central (London )
                1471-2253
                5 February 2020
                5 February 2020
                2020
                : 20
                : 38
                Affiliations
                GRID grid.412465.0, Department of Anesthesiology and Pain Medicine, , Second Affiliated Hospital, Zhejiang University School of Medicine, ; No.88 Jiefang Road, Hangzhou, 310009 China
                Author information
                http://orcid.org/0000-0002-1355-1261
                Article
                949
                10.1186/s12871-020-0949-6
                7003404
                32024468
                b334a8bc-52a8-48b6-855e-27fba302eca0
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 August 2019
                : 21 January 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Anesthesiology & Pain management
                postoperative pain,single nucleotide polymorphism,single-port video-assisted thoracoscopic surgery

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