Body's cold 'sensor' could hold key for frostbite and hypothermia treatments

A cold 'sensor' which triggers the skin's vascular response to the cold could represent an exciting new therapeutic target for the treatment of frostbite and hypothermia, according to scientists at King's College London.

Known to be linked to pain sensitivity and currently used in the development of painkillers, this is the first time the TRPA1 gene has been implicated in the response of blood vessels in the skin to cold. Published today in Nature Communications, the research was funded by the British Heart Foundation and the Biotechnology and Biological Sciences Research Council.

The human body has several defence mechanisms to try and boost its core temperature in the face of cold weather. The skin responds by narrowing its blood vessels in order to constrict the supply of blood and retain body heat (vasoconstriction). The reverse of this activity then occurs, called vasodilatation, where blood vessels are widened and more blood flows to the surface of the skin. This process is important for rewarming the skin and keeping it healthy.

In extreme cold, and especially if bare skin is open to the elements, the cold is overpowering, disrupting blood flow leading to frostbite or swelling (chilblains). The lack of warm blood reaching the skin can enhance tissue freezing and injury.

Cold weather is also a concern for older people, with Age UK estimating that several thousand die every year from the cold, independent of infection, although recent figures suggest this has fallen in 2013/14 due to milder weather.

In the King's study, the skin of anaesthetised mice was exposed to cold by immersing a paw in water. Blood flow was measured prior to this exposure and following a cooling period. Researchers found that TRPA1 acted in two distinct ways - first by sensing the change in temperature, and then by stimulating the protective constriction of blood vessels. The subsequent vasodilatation phase was also dependent on TRPA1 activation and was crucial for restoring blood flow.

Although an early study, the results offer a new understanding of TRPA1's role in cold exposure and provide impetus for further research into how this gene could be targeted to enhance the body's protective response to cold.

Susan Brain, Professor of Pharmacology in the Cardiovascular Division at King's College London, said: 'In response to cold weather the body seeks first and foremost to keep the core warm, which means retaining blood close to the centre and constricting blood supply to the skin.

'Our findings highlight the crucial role TRPA1 plays in this physiological response and could pave the way to learn of new pathways that limit the adverse effects of exposure to cold, and potentially the whole body cooling process associated with hypothermia.'

Professor Brain added: 'Next steps are to build on these promising early findings to learn more about the extent of the role of other TRP receptors in the skin's response to cold, especially as there is a large family of these temperature sensitive receptors and several of them have their own defined sensitivities to cold. Future research must also investigate the relationship between the vascular responses to cold exposure and the maintenance of skin and body temperatures.'

Professor Peter Weissberg, Medical Director at the British Heart Foundation, which part-funded the research, said: 'This study helps us to understand how and why our blood vessels contract and expand, and could help scientists develop treatments for many conditions where blood vessel or 'vascular' health is important, from Raynaud's to heart failure.

'Any research that helps to explain the complicated processes that control the circulatory system may have wide reaching implications in the future, as vascular health is involved in so many different diseases.'

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For further information please contact Jack Stonebridge, Press Officer at King's College London, on 0207 848 3238 or email jack.stonebridge@kcl.ac.uk

King's College London is one of the top 20 universities in the world (2014/15 QS World University Rankings) and the fourth oldest in England. It is The Sunday Times 'Best University for Graduate Employment 2012/13'. King's has nearly 26,000 students (of whom more than 10,600 are graduate students) from some 140 countries worldwide, and more than 7,000 staff. The College 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 £590 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.

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