Faculty of Biological Sciences

Research Bulletin

Researchers explain different mechanisms of pain

14th May 2012

The discovery of a new mechanism through which pain is signalled by nerve cells could explain the current failings in the painkiller development process and may offer opportunities for a new approach.

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.


Recent Grants

Mike McPherson (and colleagues in the School of Chemistry), EPSRC (Jul 2014), £819,880

Sheena Radford, Univesity of Michigan (Jul 2014), £138,452

Chris West, Leverhulme Trust (Jun 2014), £181,241

Jon Lippiat, Darren Tomlinson, BBSRC (May 2014), £125,174

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

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

Dave Westhead, MRC (Apr 2014), £18,304

Brendan Davies, BBSRC (Mar 2014), £451,829

Jim Deuchars, MRC (Mar 2014), £300,000

Adam Kupinski, Children with Cancer (Mar 2014), £50,000

Alison Baker, Steve Baldwin, BBSRC (Feb 2014), £403,439

Sarah Zylinski, BBSRC (Feb 2014), £355,869

Dave Lewis, Nigel Hooper, Tony Turner, Hugh Pearson, James Duce, Alzheimer's Society (Feb 2014), £29,871

Ronaldo Ichyama, Samit Chakrabarty, International Spinal Research Trust (Jan 2014), £304,600

Brendan Davies, BBSRC/Bayer Crop Science SA-NV (Jan 2014), £470,053

Adrian Goldman, Steve Baldwin, Stephen Muench, Thomas Edwards, Arwen Pearson , BBSRC (Jan 2014), £467,103

Stefan Kepinski, BBSRC (Jan 2014), £359,269

Elwyn Isaac, EU (Jan 2014), £179,445

Dave Westhead, Leukaemia & Lymphoma Research (Jan 2014), £105,937

John Barr, Thomas Edwards, MRC (Dec 2013), £469,505

Alex O'Neill, MRC (Dec 2013), £349,017

Darren Tomlinson, Yorkshire Cancer Research (Nov 2013), £142,334

Nikita Gamper, MRC (Nov 2013), £336,563

Keith Hamer, Alison Dunn, NERC (Nov 2013), £47,233

Alan Berry, Wellcome Trust (Oct 2013), £749,365

Urwin, Howard Atkinson, BBSRC (Oct 2013), £360,508

Eileen Ingham, Stacey-Paul Wilshaw, NHS R&D (Oct 2013), £356,623

Sheena Radford, BBSRC (Oct 2013), £329,906

Nigel Hooper, Alzheimer's Research (Oct 2013), £327,075

Eileen Ingham, EPSRC (Oct 2013), £276,751

David Beech, BHF (Oct 2013), £109,974

Mark Harris, Medical Research Foundation (Oct 2013), £34,455

James Dachtler, Royal Society (Oct 2013), £15,000

Ade Whitehouse, Teresa Rosenbaum Golden Charitable Trust (Oct 2013), £10,000

Jurgen Denecke, BBSRC (Sep 2013), £382,093

Andy Cuming, EU (Sep 2013), £257,714

Paul Knox, BBSRC (Sep 2013), £411,948

Vas Ponnambalam, Leverhulme Trust (Sep 2013), £245,031

Peter Meyer, EU (Sep 2013), £242,166

Dave Rowlands, Nic Stonehouse, EU (Sep 2013), £202,556

Derek Steele, BHF (Sep 2013), £103,629

Joan Boyes, NC3Rs (Sep 2013), £90,000

Peter Stockley, Royal Society (Sep 2013), £11,400

Darren Tomlinson, Leverhulme Trust (Sep 2013), £5,645

Nic Stonehouse, Dave Rowlands, BBSRC (Aug 2013), £574,906

Eileen Ingham, Wellcome Trust (Aug 2013), £191,470

Adrian Goldman, Royal Society (Aug 2013), £75,000

Mike McPherson, Wellcome Trust (Aug 2013), £40,000

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