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.
Edwin Chen, Wellcome Trust (Jul 2016), £98,341
Stefan Kepinski, Michelle Peckham, BBSRC (Apr 2016), £461,760
David Brockwell, Sheena Radford, BBSRC (Apr 2016), £358,570
Ryan Seipke, BBSRC (Apr 2016), £340,536
Neil Ranson, Mark Harris, Ade Whitehouse, Peter Stockley, Sheena Radford, Alan Berry, Wellcome Trust (Mar 2016), £1,000,000
James Duce, Alzheimer's Society (Mar 2016), £84,834
Thomas Edwards and colleagues in the School of Chemistry, EPSRC (Feb 2016), £2,228,732
Patricija Van Oosten-Hawle, Wellcome Trust (Feb 2016), £89,900
William Hoppitt, EU (Feb 2016), £34,345
Mark Harris, Thomas Edwards, John Barr and colleagues from the School of Chemistry, Wellcome Trust (Jan 2016), £204,959
Katie Field, BBSRC (Jan 2016), £830,381
Alan Berry, Alex Breeze, Adam Nelson, BBSRC (Jan 2016), £479,490
Sarah Calaghan, Isuru Jayasinghe, BHF (Jan 2016), £52,050
Paul Knox, BBSRC (Jan 2016), £40,000
Andrew Smith, Rosetrees Trust (Jan 2016), £20,000
Richard Bayliss, Cancer Research UK (Jan 2016), £10,000
Richard Bayliss, BBSRC (Jan 2016), £8,000
Richard Bayliss, MRC (Jan 2016), £8,000
Joe Cockburn, Royal Society (Dec 2015), £14,960
Katie Field, Royal Society (Dec 2015), £14,700
Stephanie Wright, Kay Kendall Leukaemia Fund (Dec 2015), £207,286
Zahra Timsah, Royal Society (Nov 2015), £15,000
Jessica Kwok, Wings For Life Spinal Cord Research (Nov 2015), £134,981
Alan Berry, Wellcome Trust (Oct 2015), £752,365
Julie Aspden, MRC (Oct 2015), £633,020
Steve Sait, NERC (Oct 2015), £386,061
Urwin, Howard Atkinson, BBSRC (Oct 2015), £200,293
Helen Miller, ABNA Ltd (Oct 2015), £115,000
Mark Harris, Royal Society (Oct 2015), £74,000
Eric Hewitt, Andrew Macdonald, Yorkshire Kidney Research Fund (Oct 2015), £46,621
Christine Foyer, Royal Society (Oct 2015), £12,000
Dave Westhead, Bloodwise (Sep 2015), £664,109
Ade Whitehouse, Alison Ashcroft, Ian Carr, BBSRC (Sep 2015), £438,975
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
Helen Miller, Agriculture & Horticulture Develpmnt Brd (Aug 2015), £63,560
Tim Benton, M & W MACK LTD (Aug 2015), £48,711
Eileen Ingham, John Fisher, EPSRC (Jul 2015), £1,458,439
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
Helen Miller, ABNA Ltd (Jul 2015), £22,968
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