The team, led by Dr Nikita Gamper of the Faculty of Biological Sciences, is investigating the difference between persistent pain, such as toothache, and pain that results from the increased sensitivity of nerves in injured or diseased tissue (for example when we touch inflamed skin), known as hyperalgesia.
In research published online this week, (w/c 14 May) in Proceedings of the National Academy of Sciences (PNAS), Dr Gamper's team has discovered that these two types of pain are generated by the same nerves, but result from different underlying mechanisms.
The project, funded jointly by the Wellcome Trust and the Medical Research Council, investigated the painful effects of two substances that cause local inflammation: bradykinin and substance P. Both substances bind to specific receptors on nerve cells, generating signals to the central nervous system. Because the receptors are from the same family, it has always been presumed they stimulate the same signalling pathway.
However, the team found that each receptor produces different signals; the one associated with bradykinin causing both hyperalgesia and persistent pain, whereas the one associated with substance P only caused hyperalgesia.
Dr Gamper says: "Pain originates from a series of electrical signals sent by nerve cells in to the central nervous system and ultimately the brain. Despite much progress, we still don't know enough about the mechanisms by which these pain signals are generated. However, this research has shown that whilst the sensation of pain can be similar between various conditions, the underlying molecular mechanisms may in fact be very different."
"Existing painkillers are 'non-specific', designed to generally dull the reception of these signals in the central nervous system, and some stronger pain killers can provoke unwanted side effects such as disorientation, drowsiness or nausea. So while the search for new better drugs is pressing, the lack of progress in developing truly targeted analgesics has led to several pharmaceutical companies dropping this area of research altogether."
"What's exciting about these findings is that substance P may actually suppress the activation of the pain sensing nerves themselves," says Dr Gamper.
"It's increasingly evident that current strategies for testing and validating new painkillers often do not take into account a possible difference in how pain signals are generated. For instance, drugs for persistent pain are often tested solely for their ability to reduce hyperalgesia, and as a result, some of the drugs that are effective in the lab, fail in subsequent clinical trials. These findings challenge current approaches in drug development research and may offer new strategies", he says.
Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521
Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015
Bill Kunin, EU (Jan 2015), £157,490
John Colyer, Leeds Teaching Hospitals Charitable Fund (Jan 2015), £40,000
Chris Hassall, Royal Society (Dec 2014), £14,500
Ryan Seipke, Royal Society (Nov 2014), £13,700
Alan Berry, Wellcome Trust (Oct 2014), £749,865
Ian Hope, Marie-Anne Shaw, BBSRC (Oct 2014), £396,565
Alison Ashcroft, Peter Stckley, Sheena Radford, Nic Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Oct 2014), £340,937
Les Firbank, Joe Holden, BBSRC (Oct 2014), £210,302
Darren Tomlinson and colleagues in Chemistry and Pathology, anatomy and Tumour Biology, Dr Hadwen Trusy (Oct 2014), £194,475
Paul Knox, EU (Oct 2014), £167,229
Martin Stacey and colleagues in Medicine & Health, Pfizer (Oct 2014), £90,453
Darren Tomlinson and colleagues in Experimental Oncology, YCR (Oct 2014), £69,480
Andrew Macdonald, Jamel Mankouri, Kidney Research Fund UK (Oct 2014), £58,878
Mike McPherson and colleagues in Dentistry and Engineering, Wellcome Trust (Oct 2014), £58,437
Dave Westhead and colleagues in Experimental Haemotology, Leukaemia & Lymphoma Research (Sep 2014), £281,424
Emmanuel Paci and colleagues in Chemistry, BBSRC (Sep 2014), £636,759
Andrew Peel, BBSRC (Sep 2014), £371,598
Lars Jeuken, Stephen Evans, BBSRC (Sep 2014), £333,684
Lars Jeuken, BBSRC (Sep 2014), £313,463
Michelle Peckham, Mark Harris, Rao Sivaprasadarao, Eileen Ingham, Nic Stonehouse, Nikita Gamper, Wellcome Trust (Sep 2014), £192,763
Neil Ranson, BBSRC (Aug 2014), £355,253
Stuart Egginton, BHF (Aug 2014), £271,094
Darren Tomlinson, Mike McPherson, Technology Strategy Board (Aug 2014), £98,665
Peter Henderson, Leverhulme Trust (Aug 2014), £15,222
Mike McPherson (and colleagues in the School of Chemistry), EPSRC (Jul 2014), £819,880
Peter Stockley, Neil Ranson, BBSRC (Jul 2014), £455,787
Sheena Radford, Univesity of Michigan (Jul 2014), £138,452
Ryan Seipke, British Society Antimicrobial Chemistry (Jun 2014), £11,960
John Trinick, BHF (Jun 2014), £222,614
Chris West, Leverhulme Trust (Jun 2014), £181,241
Jon Lippiat, Darren Tomlinson, BBSRC (May 2014), £125,174
Christine Foyer, Royal Society (May 2014), £24,000
David Brockwell, Sheena Radford, Medimmune Ltd (Apr 2014), £337,661
Peter Stockley, Wellcome Trust (Apr 2014), £251,019
Mike McPherson, Wellcome Trust (Apr 2014), £146,596
Andrew Macdonald, Kidney Research Fund UK (Apr 2014), £127,237
Elwyn Isaac, DEFRA (Apr 2014), £126,512
Mike McPherson (and colleagues in School of Design), Technology Strategy Board (Apr 2014), £114,350
Paul Millner, Peter Stockley, Darren Tomlinson, YCR (Apr 2014), £95,874
Carrie Ferguson, Karen Birch, Shaunna Burke, Heart Research UK (Apr 2014), £60,140
Tim Benton, Technology Strategy Board (Apr 2014), £24,969
Bill Kunin, Technology Strategy Board (Apr 2014), £21,244
Dave Westhead, MRC (Apr 2014), £18,304