Pain sensitivity may be influenced by lifestyle and environment, twin study suggests

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.

This is the first study to use large numbers of twins with such an in-depth examination of epigenetic signals.

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.

Lead author of the study, Dr Jordana Bell, Department of Twin Research & Genetic Epidemiology at King's College London, said: '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.'

Tim Spector, Professor of Genetic Epidemiology at King's College London, said: '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.'

This research was funded by the European Research Council (ERC) and academic grants from Pfizer Inc and the Wellcome Trust, as well as both Guy's and St Thomas' Charity and the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London.

It is just one part of a larger EU ERC EpiTwin project in collaboration with the Beijing Genomics Institute (BGI), which aims to identify the role of epigenetic factors in numerous common complex diseases, drawing on a sample of 5,000 twins from the TwinsUK cohort.

For further information please contact Katya Nasim, Press Officer at King's College London, on 0207 848 3840 or email katya.nasim@kcl.ac.uk

King's College London is one of the top 20 universities in the world (2013/14 QS World University Rankings), and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org.

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (http://www.nihr.ac.uk