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Chronic pain affects people all over the world, yet the underlying molecular mechanisms that govern it are not well understood. Now, a new UK study of twins finds that people's sensitivity to pain may be altered by changes in lifestyle and environment through life.
Individuals who are more sensitive to pain are at higher risk of developing chronic pain.
The discovery lies in a relatively new field of investigation called epigenetics, where scientists study how genes are switched on and off in response to changes in the body.
The study, led by Dr. Jordana Bell, of the Department of Twin Research & Genetic Epidemiology at King's College London, and published in Nature Communications, is the first to find that pain sensitivity may not be as inflexible as previously thought.
The findings raise the possibility that pain sensitivity might be treatable by drugs that switch certain genes off.
Unlike non-identical twins, who on average share only 50% of their genes, identical twins share 100%. So it follows that any differences in gene expression must result from processes that act on those genes, such as epigenetics, which can come through differences in environment and lifestyles. This makes identical twins ideal subjects for studying the effects of epigenetics.
For this study, the researchers recruited 25 pairs of identical twins and tested their sensitivity to pain by applying a heat probe to an arm on each twin.
They asked the participants to press a button when the heat became painful - this established their pain threshold.
Then, by sequencing the DNA obtained from participants' blood samples, the researchers pinpointed 5.2 million locations where epigenetic changes had occurred across the whole genome and compared them with those of 50 unrelated individuals.
By doing this, they could identify which parts of the genome carried epigenetic changes differentially associated with high and low pain sensitivity.
The team found epigenetic modifications in nine genes related to pain sensitivity that were different between individual twins in a pair.
One of the study's corresponding authors, Tim Spector, professor of Genetic Epidemiology at King's College London, says:
"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."
One gene in particular, TRPA1, which is already known to be involved with pain sensitivity and a target in the development of analgesics or painkillers, showed the most epigenetic changes.
However, although TRPA1 is already known to be involved with pain sensitivity, this is the first time that pain sensitivity has been linked to epigenetic changes in the gene.
The finding is important because it suggests it may be possible to switch the gene on and off with drugs and thereby change a person's pain sensitivity.
This could help people with chronic pain, Dr. Bell says:
"The potential to epigenetically regulate the behaviour 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."
Meanhwile, Medical News Today recently reported a study where a team of researchers in the US found that people's sensitivity to pain is linked to brain structure differences.
Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without the permission of Medical News Today.
Differential methylation of the TRPA1 promoter in pain sensitivity; J.T. Bell, A.K. Loomis, L.M. Butcher, F. Gao, B. Zhang, C.L. Hyde, J. Sun, H. Wu, K. Ward, J. Harris, S. Scollen, M.N. Davies, L.C. Schalkwyk, J. Mill, The MuTHER Consortium, F.M.K. Williams, N. Li, P. Deloukas, S. Beck, S.B. McMahon, and others; Nature Communications, online 4 February 2014; DOI:10.1038/ncomms3978.
Additional source: King's College London news release, 4 February 2014.
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