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Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom

BACKGROUND: The construct of multisomatoform disorder (MSD) is a common point of reference for patients in different somatic and psychosomatic specialties and therefore useful in studying large well-characterized cohorts of a prototype of a somatoform disorder and in parallel as a functional somatic...

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Autores principales: Achenbach, Johannes, Rhein, Mathias, Gombert, Sara, Meyer-Bockenkamp, Fiona, Buhck, Miro, Eberhardt, Mirjam, Leffler, Andreas, Frieling, Helge, Karst, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712620/
https://www.ncbi.nlm.nih.gov/pubmed/31455424
http://dx.doi.org/10.1186/s13148-019-0731-0
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author Achenbach, Johannes
Rhein, Mathias
Gombert, Sara
Meyer-Bockenkamp, Fiona
Buhck, Miro
Eberhardt, Mirjam
Leffler, Andreas
Frieling, Helge
Karst, Matthias
author_facet Achenbach, Johannes
Rhein, Mathias
Gombert, Sara
Meyer-Bockenkamp, Fiona
Buhck, Miro
Eberhardt, Mirjam
Leffler, Andreas
Frieling, Helge
Karst, Matthias
author_sort Achenbach, Johannes
collection PubMed
description BACKGROUND: The construct of multisomatoform disorder (MSD) is a common point of reference for patients in different somatic and psychosomatic specialties and therefore useful in studying large well-characterized cohorts of a prototype of a somatoform disorder and in parallel as a functional somatic syndrome (FSS). This disorder is characterized by distressing and functionally disabling somatic symptoms with chronic pain as the most frequent and clinically relevant complaint. Pain is perceived by nociceptive nerve fibers and transferred through the generation of action potentials by different receptor molecules known to determine pain sensitivity in pathophysiological processes. Previous studies have shown that for the transient receptor potential ankyrin 1 (TRPA1), receptor methylation of a particular CpG dinucleotide in the promoter region is inversely associated with both heat pain and pressure pain thresholds. In this study, we hypothesized that TRPA1 promoter methylation regulates pain sensitivity of patients with multisomatoform disorder (MSD). A cohort of 151 patients with MSD and 149 matched healthy volunteers were evaluated using quantitative sensory testing, clinical and psychometric assessment, and methylation analysis using DNA isolated from whole blood. RESULTS: We found CpG -628 to be correlated with mechanical pain threshold and CpG -411 to be correlated with mechanical pain threshold in female volunteers, i.e., higher methylation levels lead to higher pain thresholds. A novel finding is that methylation levels were significantly different between patients with no and severe levels of childhood trauma. CpG methylation also correlated with psychometric assessment of pain and pain levels rated on a visual analog scale. CONCLUSION: Our findings support the hypothesis that epigenetic regulation of TRPA1 plays a role in mechanical pain sensitivities in healthy volunteers. They further provide evidence for the possible influence of childhood traumatic experiences on the epigenetic regulation of TRPA1 in patients with MSD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-019-0731-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-67126202019-08-29 Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom Achenbach, Johannes Rhein, Mathias Gombert, Sara Meyer-Bockenkamp, Fiona Buhck, Miro Eberhardt, Mirjam Leffler, Andreas Frieling, Helge Karst, Matthias Clin Epigenetics Research BACKGROUND: The construct of multisomatoform disorder (MSD) is a common point of reference for patients in different somatic and psychosomatic specialties and therefore useful in studying large well-characterized cohorts of a prototype of a somatoform disorder and in parallel as a functional somatic syndrome (FSS). This disorder is characterized by distressing and functionally disabling somatic symptoms with chronic pain as the most frequent and clinically relevant complaint. Pain is perceived by nociceptive nerve fibers and transferred through the generation of action potentials by different receptor molecules known to determine pain sensitivity in pathophysiological processes. Previous studies have shown that for the transient receptor potential ankyrin 1 (TRPA1), receptor methylation of a particular CpG dinucleotide in the promoter region is inversely associated with both heat pain and pressure pain thresholds. In this study, we hypothesized that TRPA1 promoter methylation regulates pain sensitivity of patients with multisomatoform disorder (MSD). A cohort of 151 patients with MSD and 149 matched healthy volunteers were evaluated using quantitative sensory testing, clinical and psychometric assessment, and methylation analysis using DNA isolated from whole blood. RESULTS: We found CpG -628 to be correlated with mechanical pain threshold and CpG -411 to be correlated with mechanical pain threshold in female volunteers, i.e., higher methylation levels lead to higher pain thresholds. A novel finding is that methylation levels were significantly different between patients with no and severe levels of childhood trauma. CpG methylation also correlated with psychometric assessment of pain and pain levels rated on a visual analog scale. CONCLUSION: Our findings support the hypothesis that epigenetic regulation of TRPA1 plays a role in mechanical pain sensitivities in healthy volunteers. They further provide evidence for the possible influence of childhood traumatic experiences on the epigenetic regulation of TRPA1 in patients with MSD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-019-0731-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-28 /pmc/articles/PMC6712620/ /pubmed/31455424 http://dx.doi.org/10.1186/s13148-019-0731-0 Text en © The Author(s). 2019 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.
spellingShingle Research
Achenbach, Johannes
Rhein, Mathias
Gombert, Sara
Meyer-Bockenkamp, Fiona
Buhck, Miro
Eberhardt, Mirjam
Leffler, Andreas
Frieling, Helge
Karst, Matthias
Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
title Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
title_full Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
title_fullStr Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
title_full_unstemmed Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
title_short Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
title_sort childhood traumatization is associated with differences in trpa1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712620/
https://www.ncbi.nlm.nih.gov/pubmed/31455424
http://dx.doi.org/10.1186/s13148-019-0731-0
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