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.
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Jennifer Tomlinson, Royal Society-Research Fellows Enhancement Award (Dec 2017), £94,681
Helen Miller, AB AGri Grant (Dec 2017), £73,600
Simon Walker, Royal Society Enhancement Award (Dec 2017), £10,000
Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
Ralf Richter, Royal Society (Dec 2017), £6,000
Christine Foyer, British Council Newton Fund (Dec 2017), £49,840
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
Neil Ranson, Juan Fontana, Mark Harris, Michelle Peckham, Ralf Richter, Peter Stockley, Patricija Van Oosten-Hawle and colleagues in Engineering, FMH and MAPS, Wellcome Trust Equipment Call (Sep 2017), £418,000
Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576
Sheena Radford, Wellcome Trust (Mar 2017), £1,836,482
Beatrice Filippi, Royal Society (Mar 2017), £15,000
Tom Bennett, Royal Society (Mar 2017), £15,000
Jamie Johnston, Royal Society (Mar 2017), £15,000
Ryan Seipke, BBSRC (Feb 2017), £52,116
Mary O'Connell, BBSRC (Feb 2017), £46,986
Hannah Dugdale, NERC (Feb 2017), £504,138
Anastasia Zhuravleva, EPSRC (Jan 2017), £100,792