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

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

Recent
News

Bats wake up and smell the coffee

20th August 2015

Intensive agriculture is taking a toll on bats in the Western Ghats of India, one of the world’s most biodiverse regions, but shade-grown coffee, remnant rainforest patches and riverine vegetation strips may help struggling species hang on.


Food production shocks 'will happen more often because of extreme weather'

14th August 2015

Professor Tim Benton (biology), from University of Leeds has conducted research that suggests climate change and a rising demand in food from a high population could cause a frightening situation. 


“Brainy” mice raise hope of better treatments for cognitive disorders

14th August 2015

Researchers have created unusually intelligent mice by altering a single gene and as a result the mice were also less likely to feel anxiety or recall fear. 


Study finds non-genetic cancer mechanism

27th July 2015

Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found.


Physiological Society Oral Communication Prize Winners

17th July 2015

Ewan Fowler and Sabine Lotteau from the Cardiovascular, Sport and Exercise Sciences group (School of Biomedical Sciences) have been awarded the Physiological Society’s Oral Communication Prizes


Age doesn’t dull damselflies' love lives

16th July 2015

Aging damselflies never lose their libidos and are just as likely as younger competitors to mate.


The University of Leeds is investing in 250 new academic fellowships.

1st July 2015

Are you one of the 250 Great Minds we are looking for?


Leeds academics recognised for teaching excellence

11th June 2015

Two University of Leeds academics have received a prestigious teaching award, a National Teaching Fellowship.


The Quest to Engineer the Perfect Potato

8th June 2015

Researchers in the U.K. aim for a new commercial potato that resists many of the worst vulnerabilities of potato crops around the world.


Impact
Stories

Professor Sheena Radford has undertaken research to determine how peptides self-aggregate and form fibrils under certain conditions.

The Yorkshire Dales Environment Network is a partnership involved in the daily life and long term protection of the Yorkshire Dales.

Professors Urwin and Atkinson have developed three novel technologies for nematode control.

Professor Miller has demonstrated a weanling pig feed formulation which avoids the use of antibiotics.

All impact stories