Pain sensitivity changes due to lifestyle, environment

Pain sensitivity may be influenced by lifestyle, environment, twin study suggests — ScienceDaily — February 4, 2014

Researchers at King’s College London have discovered that sensitivity to pain could be altered by a person’s lifestyle and environment throughout their lifetime.

The study is the first to find that pain sensitivity, previously thought to be relatively inflexible, can change as a result of genes being switched on or off by lifestyle and environmental factors — a process called epigenetics, which chemically alters the expression of genes.

Published today in Nature Communications, the study has important implications for understanding pain sensitivity and could lead to new treatments aimed at ‘switching off’ certain genes epigenetically.  

Identical twins share 100 per cent of their genes, whereas non-identical twins share on average only half of the genes that vary between people. Therefore, any difference between identical twins must be due to their environment or epigenetic changes affecting the function of their genes, making them ideal participants for a study of this nature.

To identify levels of sensitivity to pain, scientists tested 25 pairs of identical twins using a heat probe on the arm. Participants were asked to press a button when the heat became painful for them, which allowed the researchers to determine their pain thresholds. Using DNA sequencing, the researchers examined over five million epigenetic marks across the whole genome and compared them with a further 50 unrelated individuals to confirm their results.

The research team

  • found wide variations between people and
  • identified chemical modifications within nine genes involved in pain sensitivity that were different in one twin but not in her identical sister.

The chemical changes were most significant within a known pain sensitivity gene, TRPA1, already a therapeutic target in the development of painkillers (analgesics).

This is the first time TRPA1 has shown the capacity to be switched on and off epigenetically; finding out how this happens could have major implications for tackling pain relief. It is well established that people who are most sensitive to pain encountered in everyday life are more likely to go on to develop chronic pain.

Epigenetic switching is like a dimmer switch for gene expression. This landmark study shows how identical twins, when combined with the latest technology to look at millions of epigenetic signals, can be used to find the small chemical switches in our genes that make us all unique — and in this case respond to pain differently.’

Journal Reference:

Differential methylation of the TRPA1 promoter in pain sensitivity | Nat Commun. 2014 Feb 4 | Free full-text PMC article

Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals.

Whole-blood DNA methylation was characterized at 5.2 million loci by MeDIP sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain sensitivity (pain DMRs).

Nine meta-analysis pain DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2 × 10−13).

Several pain DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in the brain and altered expression in the skin.

Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits.  

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