Discovery of 'mini-brains' could change understanding of pain medication

April 4, 2017, University of Leeds
Ganglia. Credit: Nikita Gamper, University of Leeds

The human body's peripheral nervous system could be capable of interpreting its environment and modulating pain, neuroscientists have established, after successfully studying how rodents reacted to stimulation.

Until now, accepted scientific theory has held that only the central nervous system - the brain and spinal cord - could actually interpret and analyse sensations like pain or heat.

The peripheral system that runs throughout the body was seen to be a mainly wiring network, relaying 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 the 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 previously believed to be restricted to the central nervous system.

The findings are published today in the Journal of Clinical Investigation and have potential future implications for the development of new painkillers, including drugs to target backache and arthritis pain.

Pain relief drugs

Current pain relief drugs are targeted at the central nervous system and often have side effects including 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 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.

Nerve arrangements

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 .

"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."

Research Council support

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."

A view from industry

Lishuang Cao, head of Membrane Physiology at GlaxoSmithKline R&D in Shanghai commented on this research: "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 pain killers.

"Further work is needed to understand the physiological role of GABA in painful situations like inflammatory, neuropathic and chronic . More importantly we need to know if the same mechanism is present in human beings' peripheral nervous systems."

Explore further: 'Pain paradox' discovery provides route to new pain control drugs

More information: Xiaona Du et al, Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission, Journal of Clinical Investigation (2017). DOI: 10.1172/JCI86812

Related Stories

'Pain paradox' discovery provides route to new pain control drugs

July 28, 2016
A natural substance known to activate pain in the central nervous system has been found to have the opposite effect in other parts of the body, potentially paving the way to new methods of pain control.

Understanding the causes of neurological abnormalities that result from premature birth

January 3, 2017
In the February issue of the American Journal of Pathology, new research from the University of Chicago shows motor abnormalities frequently associated with low birth weight babies could originate due to peripheral nerve ...

New research may pave the way for peripheral nerve damage repair

January 30, 2017
Research published today, 30th January 2017 online in the Journal of Cell Biology, has for the first time identified how a bodily protein allows nerves of the peripheral nervous system (PNS) to repair following injury.

Study identifies specific gene network that promotes nervous system repair

February 19, 2016
Whether or not nerve cells are able to regrow after injury depends on their location in the body. Injured nerve cells in the peripheral nervous system, such as those in the arms and legs, can recover and regrow, at least ...

Blocking neuron signaling pathway could lead to new treatments for peripheral neuropathy

January 17, 2017
Researchers at University of California San Diego School of Medicine, with colleagues at the National Institute of Diabetes and Digestive and Kidney Diseases, the University of Manitoba and St. Boniface Hospital Albrechtsen ...

Recommended for you

Often overlooked glial cell is key to learning and memory

June 18, 2018
Glial cells surround neurons and provide support—not unlike hospital staff and nurses supporting doctors to keep operations running smoothly. These often-overlooked cells, which include oligodendrocytes and astrocytes, ...

Neuroscientists map brain's response to cold touch

June 18, 2018
Carnegie Mellon University neuroscientists have mapped the feeling of cool touch to the brain's insula in a mouse model. The findings, published in the June 15 issue of Journal of Comparative Neurology, provide an experimental ...

Electrically stimulating the brain may restore movement after stroke

June 18, 2018
UC San Francisco scientists have improved mobility in rats that had experienced debilitating strokes by using electrical stimulation to restore a distinctive pattern of brain cell activity associated with efficient movement. ...

Silence is golden when it comes to how our brains work

June 18, 2018
It's the comparative silence between the firing spikes of neurons that tells what they are really up to, scientists report.

iReadMore app improves reading ability of stroke patients

June 18, 2018
A new smart app designed to improve the reading ability of people who have suffered a stroke provides 'significant' improvements, a UCL study has found.

Observing brain plasticity during cello training

June 15, 2018
Music acquisition provides an excellent model of neural plasticity, and has become a hot research subject in neurology. Music performance provides an unmatched array of neural complexities revealing how neural networks are ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.