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.
Neil Ranson, Mark Harris, Ade Whitehouse, Peter Stockley, Sheena Radford, Alan Berry, Wellcome Trust (Mar 2016), £1,000,000
Alan Berry, Wellcome Trust (Oct 2015), £752,365
Steve Sait, NERC (Oct 2015), £386,061
Urwin, Howard Atkinson, BBSRC (Oct 2015), £200,293
Eric Hewitt, Andrew Macdonald, Yorkshire Kidney Research Fund (Oct 2015), £46,621
Ade Whitehouse, Alison Ashcroft, Ian Carr, BBSRC (Sep 2015), £438,975
Dave Westhead, Leukaemia & Lymphoma Research
Leukaemia & Lymphoma Research (Sep 2015), £430,567
Shaunna Burke, Andrea Utley, Sarah Astill, Arts Council of England (Sep 2015), £80,594
Samit Chakrabarty, Ronaldo Ichiyama, Intl Foundn for Research in Paraplegia (Aug 2015), £93,000
Anastasia Zhuravleva, BBSRC (Jul 2015), £483,019
Alex O'Neill, MRC (Jul 2015), £249,822
Ade Whitehouse, Richard Foster, Cancer Research UK (Jul 2015), £201,034
Ronaldo Ichiyama, Jim Deuchars, Sue Deuchars, Wings For Life Spinal Cord Research (Jul 2015), £123,895
Martin Stacey and colleagues in FMH, MRC (Jun 2015), £426,475
Adrian Goldman, Sarah Harris, Roman Tuma, BBSRC (Jun 2015), £420,693
Elwyn Isaac, EU (Jun 2015), £238,915
Christine Foyer, BBSRC (Jun 2015), £160,401
Adrian Goldman, EU (Jun 2015), £116,331
David Brockwell, Sheena Radford, Innovate UK (Jun 2015), £113,378
Yoselin Benitez-Alfonso, EPSRC (Jun 2015), £93,672
Michelle Peckham, Peter Knight, Thomas Edwards, BBSRC (May 2015), £404,987
Michelle Peckham, Ed White, Peter Knight, BHF (May 2015), £208,184
Dave Westhead, Sheena Radford, Alex Breeze, BBSRC (May 2015), £51,021
Steve Clapcote, Vitaflo International Ltd (May 2015), £33,703
Les Firbank, Joe Holden, Pippa Chapman, NERC (Apr 2015), £388,726
Samit Chakrabarty, David Steenson, BBSRC (Apr 2015), £120,103
Paul Millner, Gin Jose, Sarah Aickin, DSTL Porton Down (Apr 2015), £63,407
Chris Hassell, David Lewis, The Physiological Society (Apr 2015), £6,900
Andrew Tuplin, Royal Society (Mar 2015), £15,000
Yoselin Benitez-Alfonso, Royal Society (Mar 2015), £14,770
Patricija Van Oosten-Hawle, Royal Society (Mar 2015), £13,960
Stuart Egginton, BHF (Mar 2015), £272,979
Keith Hamer, Department of Energy & Climate Change (Mar 2015), £58,066
Andrew Macdonald, Yorkshire Kidney Research Fund (Mar 2015), £41,171
Les Firbank, DEFRA Dept for Env. Food & Rural Affairs (Feb 2015), £20,000
Ian Hope, Marie-Anne Shaw, BBSRC (Jan 2015), £381,998
Paul Knox, BBSRC (Jan 2015), £5,000
Andrew Peel, BBSRC (Jan 2015), £359,077
Christine Foyer, BBSRC (Jan 2015), £408,334
Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521
Mike McPherson, Christoph Walti, DSTL Porton Down (Jan 2015), £625,125
Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015
Alison Ashcroft, Peter Stockley, Sheena Radford, Nicola Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Jan 2015), £340,937
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
Neil Ranson, BBSRC (Nov 2014), £355,253
Alan Berry, Wellcome Trust (Oct 2014), £749,865
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