title: Epigenetic divergence in the TRPA1 promoter correlates with pressure pain thresholds in healthy individuals.
abstract: The expression pattern of important transduction molecules in nociceptive sensory neurons is likely to dictate pain sensitivity. While this notion is well established for increased pain sensitivities under conditions like inflammation and neuropathy, less is known as to which molecules are defining interindividual differences in pain sensitivity in healthy subjects. A genome-wide methylation analysis on monozygotic twins found that methylation of a CpG dinucleotide in the promoter of transient receptor potential ankyrin 1 (TRPA1) is inversely associated with the threshold for heat-induced pain. Several in vitro studies also suggest that TRPA1 mediates mechanical sensitivity of sensory afferents, thus potentially mediating pressure-evoked pain. In the present study, we therefore investigated the epigenetic predisposition for pressure pain by analyzing the methylation status of 47 CpG sites in the promoter region of TRPA1. Using DNA from whole-blood samples of 75 healthy volunteers, we found that the same CpG site previously found to affect the threshold for heat-evoked pain is hypermethylated in subjects with a low threshold for pressure pain. We also found gender differences, with females displaying higher methylation rates combined with higher pressure pain sensitivities as compared with males. In conclusion, our findings support the notion that epigenetic regulation of TRPA1 seems to regulate thermal and mechanical pain sensitivities.
authors.affiliation: Laboratory for Molecular Neuroscience, Department of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Gombert
authors.affiliation: Laboratory for Molecular Neuroscience, Department of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Rhein
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Eberhardt
authors.affiliation: Department of Anesthesiology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Tino
authors.initials: T
authors.lastname: Münster
authors.affiliation: Laboratory for Molecular Neuroscience, Department of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Leffler
authors.affiliation: Laboratory for Molecular Neuroscience, Department of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015220:Calcium Channels / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D064368:Healthy Volunteers; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017288:Pain Threshold / Q000502:physiology*; D011312:Pressure / Q000009:adverse effects; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012727:Sex Characteristics; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels