• Pain · Apr 2017

    Epigenetic divergence in the TRPA1 promoter correlates with pressure pain thresholds in healthy individuals.

    • Sara Gombert, Mathias Rhein, Mirjam Eberhardt, Tino Münster, Stefan Bleich, Andreas Leffler, and Helge Frieling.
    • aLaboratory for Molecular Neuroscience, Department of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany bDepartment of Anesthesiology and Intensive Care Medicine, H... more annover Medical School, Hannover, Germany cDepartment of Anesthesiology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. less
    • Pain. 2017 Apr 1; 158 (4): 698-704.

    AbstractThe 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.

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