A lifetime of stress, depression and anxiety can make genes more sensitive to pain, according to a new study of identical twins in England. The findings may help explain how mild pain becomes acute or how acute pain become chronic – and could lead to new treatments to relieve pain.
The study, published online in Nature Communications, is the first to show that genes can be switched on and off by lifestyle and environmental factors — a process called epigenetics, which chemically alters the expression of genes.
“Epigenetic switching is like a dimmer switch for gene expression,” said Tim Spector, the senior author of the study and a professor of Genetic Epidemiology at King’s College London.
“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.”
King’s College researchers made the discovery while studying the pain tolerance of 50 identical female twins. Although the twins were born with the same DNA, by the time the women reached middle age differences appeared in their genes and sensitivity to pain.
To identify the degree of pain sensitivity in each twin, scientists put a heat probe on their forearms and gradually turned the temperature higher. Participants would say when the temperature changed from “painful” to “unbearable”, and the experiment would then be stopped.
The researchers then chose the 25 pairs of identical twins that had the largest differences in pain sensitivity and analyzed their DNA through blood samples. After examining over five million epigenetic marks across the whole genome, they found chemical modifications in nine genes that were different in one twin but not in her identical sister. The chemical changes were most significant in the “pain gene” known as TRPA1, which is already a therapeutic target in the development of painkillers.
This was the first time TRPA1 has shown the capacity to be switched on and off epigenetically. The study did not identify what lifestyle or environmental factors may have contributed to the changes. Finding out how and why the genes changed could have major implications in developing non-opioid drugs to relieve pain.
“The potential to epigenetically regulate the behavior of TRPA1 and other genes involved in pain sensitivity is very exciting and could lead to a more effective pain relief treatment for patients suffering with chronic pain,” said lead author Dr. Jordana Bell, Department of Twin Research & Genetic Epidemiology at King’s College London.