Research at the University of Leeds could pave the way to a new generation of painkillers by providing a new theory of how inflammation causes pain.
An international group of scientists led by Dr Nikita Gamper of the University's Faculty of Biological Sciences has discovered how two proteins play a key role in the way we feel pain, offering new targets on which drug development can be focused. The findings are published online today (March 24) in the Journal of Clinical Investigation.
"Pain originates from a series of electrical signals sent by nerve cells in outlying areas of the body to the central nervous system and ultimately the brain," said Dr Gamper. "We still know very little about the mechanism by which these signals are generated, so existing painkillers are non-specific, designed to generally dull the reception of the signals in the central nervous system.
"Because they target the central nervous system, some stronger pain killers can provoke severe side effects, such as disorientation, drowsiness or nausea - and many of these drugs are addictive. Our research is trying to better understand where pain originates, to enable more targeted drugs to be developed that avoid these side effects." Pain can be a healthy response, informing us that something in our bodies is going wrong, is damaged or at risk of being damaged.
Inflammation often distorts this healthy reaction, causing pain that lasts much longer than is needed to transmit the message, as is the case in toothache, sore throat or arthritis. In research funded jointly by the Wellcome Trust and the Medical Research Council, Dr Gamper's team has discovered that a substance released at sites of inflammation - called bradykinin - manipulates two proteins commonly found at the damage-sensing terminals of peripheral nerve cells.
When targeted by the bradykinin, these proteins then cause the nerve cells to send electrical 'pain' signals to the brain. The research offers a new concept of how inflammation can cause pain and is the first time that one of these proteins - Calcium-activated chloride channel Ano1 - has been shown to have a role in pain transmission.
The other protein, called M-type potassium channel, although previously linked to neuronal activity, was not known to have a role in inflammatory pain. "The process we've identified takes place in the peripheral sensing neurons where the pain signal is generated," said Dr Gamper.
"Targeting the peripheral nervous system for drug development would create painkillers that would leave the central nervous system untouched, thus reducing the likelihood of side effects." Dr Gamper is now planning to study these proteins in more depth and identify their possible role in other types of pain, such as neuropathic pain and migraine.
For further information:
Please contact the University of Leeds Press Office on +44 (0)113 343 4031 or email firstname.lastname@example.orgNotes to editors:
- Dr Nikita Gamper is a lecturer in the Institute of Membrane and Systems Biology in the Faculty of Biological Sciences at the University of Leeds.
- The Faculty of Biological Sciences at the University of Leeds is one of the largest in the UK, with over 150 academic staff and over 400 postdoctoral fellows and postgraduate students. The Faculty is ranked 4th in the UK (Nature Journal, 457 (2009) doi :10.1038/457013a) based on results of the 2008 Research Assessment Exercise (RAE). The RAE feedback noted that "virtually all outputs were assessed as being recognized internationally, with many (60%) being internationally excellent or world-leading" in quality. The Faculty's research grant portfolio totals some £60M and funders include charities, research councils, the European Union and industry. http://www.fbs.leeds.ac.uk/
- The 2008 Research Assessment Exercise showed the University of Leeds to be the UK's eighth biggest research powerhouse. The University is one of the largest higher education institutions in the UK and a member of the Russell Group of research-intensive universities. The University's vision is to secure a place among the world's top 50 by 2015. http://www.leeds.ac.uk/
- For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. http://www.mrc.ac.uk/
- The Wellcome Trust is a global charity 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. http://www.wellcome.ac.uk/