Researchers at King's College London have found a molecule in the body which controls sensitivity to pain from UVB irradiation, identifying it as a new target for medicines to treat pain caused by other common inflammatory conditions such as arthritis.
The molecule, called CXCL5, is part of a family of proteins called chemokines, which recruit inflammatory immune cells to the injured tissue, triggering pain and tenderness. This is the first study to reveal this molecule's role in mediating pain.
The study, funded by the Wellcome Trust (as part of the London Pain Consortium), and the UK's Biotechnology and Biological Sciences Research Council (BBSRC), is to be published in the journal Science Translational Medicine.
The research teams, led by Professor Stephen McMahon and Dr David Bennett at King's College London, carried out a simple procedure in healthy human volunteers, to expose small patches of their skin to UVB irradiation, creating a small area of sunburn. The treated skin became tender over the following hours, with peak sensory change one to two days later. At this peak the researchers took small biopsies of the affected skin and analyzed the tissue for hundreds of pain mediators.
They found that several of these mediators were over-expressed, so they then examined the biology of these factors in rats to find out whether they were likely to be responsible for driving the pain in the sunburnt skin.
The mediator CXCL5 was significantly over-expressed in the human biopsies and the biology of this chemokine in rats, which suggests it is responsible for a significant amount of sensitivity in the sunburn.
Further tests carried out on the rats showed that a neutralising antibody targeting CXCL5 significantly reduced the sensitivity to pain caused by the UVB irradiation.
Professor Steve McMahon, from the Wolfson Centre for Age-Related Diseases at King's and head of the London Pain Consortium, said: 'These findings have shown for the first time the important role of this particular molecule in controlling pain from exposure to UVB irradiation. But this study isn't just about sunburn – we hope that we have identified a potential target which can be utilised to understand more about pain in other inflammatory conditions like arthritis and cystitis.
'I'm excited about where these findings could take us in terms of eventually developing a new type of analgesic for people who suffer from chronic pain.'
The researchers say that not only are the findings of importance for understanding the aetiology of pain, but the approach they used by first identifying the mechanisms in humans and then looking at these in pre-clinical animal models is a novel one in the field of pain research.
Dr David Bennett, Wellcome clinical scientist at King's and honorary consultant neurologist at King's College Hospital, said: 'Traditionally scientists have first studied the biology of diseases in animal models to identify mechanisms relevant to creating that state. But this often does not translate into effective treatments in the clinic. What we have done is reverse this traditional method by identifying putative mediators in humans first, and then exploring this further in rats. This enabled us to see that the rats' response to these pain mediators closely parallel those occurring in humans and identify mechanisms of action in the preclinical studies.
'We intend to extend this approach to other types of pain and in particular to study patients suffering from chronic pain with the hope that this will speed up the process of turning science into effective treatments for patients.
'Improving healthcare by translating research more rapidly into clinical practice in this way is at the heart of our Academic Health Sciences Centre, King's Health Partners.'
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King's College London
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Notes to editors:
UVB Irradiation–Induced Pain Is Mediated by CXCL5, Science Translational Medicine A copy of the paper and images are available from the King's Press Office
King's College London (www.kcl.ac.uk)
King's College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times 'University of the Year 2010/11' 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. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.
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: www.kingshealthpartners.org.
About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
A video about the work of the London Pain Consortium can be viewed at http://www.youtube.com/watch?v=asHQUBF7BFE.
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