Until now, accepted scientific theory has held that only the central nervous system – the brain and spinal cord – could actually interpret and analyse sensations such as pain or heat.
The peripheral system that runs throughout the body was seen to be a mainly wiring network, relaying information to and from the central nervous system by delivering messages to the ‘control centre’ (the brain), which then tells the body how to react.
In recent years there has been some evidence of a more complex role for the peripheral nervous system, but this study by Hebei Medical University in China and the University of Leeds highlights a crucial new role for the ganglia, a collection of ‘nodules’.
Previously these were believed to act only as an energy source for messages being carried through the nervous system. In addition, researchers now believe they also have the ability to act as ‘mini-brains’, modifying how much information is sent to the central nervous system.
The five year study found that nerve cells within the ganglia can exchange information between each other with the help of a signalling molecule called GABA, a process that was previously believed to be restricted to the central nervous system.
Current pain relief drugs are targeted at the central nervous system and often have side effects that can include addiction and tolerance issues.
The new research opens up the possibility of a route for developing non-addictive and non-drowsy drugs, targeted at the peripheral nervous system. Safe therapeutic dosage of these new drugs can also be much higher, potentially resulting in higher efficacy.
Whilst the study showed a rodent’s peripheral nervous system was able to interpret the type of stimulation it was sensing, further research is still needed to understand how sensations are interpreted and whether these results apply to humans.
In addition, the theory would need to be adopted by drug development companies and extensively tested before laboratory and clinical trials of a drug could be carried out. Should the findings be adopted, a timescale of at least 15-20 years might be required to produce a working drug.
Neuroscientist Professor Nikita Gamper, who led the research at both universities, said: “We found the peripheral nervous system has the ability to alter the information sent to the brain, rather than blindly passing everything on to the central nervous system.
“We don’t yet know how the system works, but the machinery is definitely in place to allow the peripheral system to interpret and modify the tactile information perceived by the brain in terms of interpreting pain, warmth or the solidity of objects.
“Further research is needed to understand exactly how it operates, but we have no reason to believe that the same nerve arrangements would not exist in humans.
“When our research team looked more closely at the peripheral system, we found the machinery for neuronal communication did exist in the peripheral nervous system’s structure. It is as if each sensory nerve has its own ‘mini-brain’, which to an extent, can interpret incoming information.”
Co-author of the study, Professor Xiaona Du from Hebei Medical University, added: “This dramatically changes our understanding of pain medication because in theory it is now possible to target drugs at the peripheral nervous system which could widen the type of treatments available.”
Professor Gamper believes the findings may present a challenge to the accepted ‘Gate Control Theory of Pain’. The theory holds that a primary ‘gate’ exists between the peripheral and central nervous systems, controlling what information is sent to the central system.
The study now suggests the transmission of information to the central nervous system must go through another set of gates, or more accurately a process similar to a volume control, where the flow of information can be controlled by the peripheral nervous system.
“Peripheral nerves have the ability to dial up or down the signal which goes through these gates to the brain”, said Professor Gamper. “Importantly, we believe that these gates can be exploited for therapeutic control of pain.”
Dr Kathryn Adcock, Head of Neurosciences and Mental Health at the Medical Research Council, which part-funded the work, said: “These findings are an interesting step in advancing scientists’ understanding of the mechanisms underpinning pain perception. We are committed to supporting work such as this to aid the continued search for new and better pain treatments.”
Lishuang Cao, head of Membrane Physiology at GlaxoSmithKline R&D in Shanghai, said: “This interesting finding could pave the way for developing novel pain medicines by targeting the peripheral GABA signaling pathway and at the same time avoiding or reducing the side effects of many existing painkillers.
“Further work is needed to understand the physiological role of GABA in painful situations like inflammatory, neuropathic and chronic pain. More importantly we need to know if the same mechanism is present in human beings’ peripheral nervous systems.”
Professor Nikita Gamper is available to be interviewed, contact Peter Le Riche in the University of Leeds press office on 0113 343 4031 or email email@example.com.
The research was funded by Hebei Medical University, the National Natural Science Foundation of China, Hebei Province and the Medical Research Council in the UK.
To test their findings, the researchers developed several new approaches as well as using rats and mice in the study. They grew neurons in a petri dish under lab conditions and tested their interaction with the use of ‘sniffing cells’, which detected and reported signals released by neurons for communication with each other. They also developed ways to trigger and manipulate peripheral nerve communication in freely behaving rodents using optical, chemical and genetic manipulations.
Steve Clapcote, Jamie Johnston, The Dunhill Medical Trust (Jun 2018), £254,874
Adrian Goldman, MRC (Jun 2018), £98,627
Darren Tomlinson, Michelle Peckham, Megan Wright, BBSRC (Jun 2018), £150,443
Simon Walker, Royal Society (Jun 2018), £337,601
Tom Thirkell, N8 Agrifood (Jun 2018), £14,870
Stephen Muench with Glaxo SmithKline & UCB Celltech, BBSRC Industrial Partnership Award (Apr 2018), £480,225
Steve Clapcote, BBSRC (Apr 2018), £443,072
Helen Miller, Innovate UK (Apr 2018), £999,960
Elisabetta Groppelli, David Rowlands & Stanley Lemon (University of North Carolina), Medical Research Foundation Fellowship (Apr 2018), £293,494
Nikesh Patel, Medical Research Foundation fellowship (Apr 2018), £290,976
Graham Askew with colleagues in Hull and Liverpool, BBSRC (Apr 2018), £150,498
Andrew Macdonald, Neil Ranson & Richard Foster, Kidney Research UK (Apr 2018), £82,821
Jessica Kwok & Ralf Richter, Leverhulme Trust (Apr 2018), £298,273
Julie Aspden, Royal Society (Apr 2018), £20,000
Liz Duncan, Royal Society (Mar 2018), £14,602
Alex O'Neill & Ryan Seipke, BBSRC (Feb 2018), £45,489
Jim Deuchars, Royal Society (Feb 2018), £16,300
Stefan Kepinski & Netta Cohen, Leverhulme Trust (Feb 2018), £320,387
Lisa Collins, BBSRC (Feb 2018), £49,950
Alison Baker, BBSRC (Feb 2018), £30,000
Lars Jeuken, BBSRC (Feb 2018), £30,000
Nikita Gamper, BBSRC (Feb 2018), £30,000
Scott Bowen, Leducq Foundation Grant (Feb 2018), £28,470
Jessica Kwok and Ronaldo Ichiyama, International Spinal Research Trust (Feb 2018), £94,450
Alex O'Neill, Oxford Drug Design (Jan 2018), £86,098
Dave Lewis and Colleagues in South Africa, HEFCE Global Challenge Research (Jan 2018), £48,000
Sarah Calaghan, Ed White, John Colyer, Isuru Jayasinghe, BHF (Jan 2018), £128,308
Christine Foyer and Alison Baker, HEFCE GCRF Grant (Jan 2018), £71,158
Alison Baker, Yun Yung Gong and Lindsay Stringer and ICRISAT India, HEFCE GCRF Grant (Jan 2018), £27,000
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Alison Dunn, NERC (Dec 2017), £18,000
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