'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.

The discovery could explain the repeated - and costly - failure over the last 20 years of of potential pain-killing drugs that targeted the substance, known as 'Substance P'.

Substance P is produced in both the central nervous system (CNS) - the brain and spinal cord - and in our peripheral nervous system (PNS) - all the other nerves and nerve cells that send signals to the brain.

The new research, by the Hebei Medical University in China and the University of Leeds in the UK, has found that, in the peripheral nervous system, Substance P makes nerve cells less responsive and excitable, thereby reducing sensations of pain. This is in direct contrast to its role in the central nervous system, where it triggers very different signals, exciting neurons and so promoting pain.

Lead researcher Professor Nikita Gamper, from the University of Leeds, explains: "We were really surprised by the results - Substance P is described in the literature as a molecule that gets nerve cells excited and promotes pain. But we've discovered a paradox - that in the peripheral nervous system it acts as one of the body's natural painkillers and actually suppresses pain.

"This means that when drugs were used in trials to suppress Substance P's action in the central nervous system, they may have also prevented it from acting as a painkiller in the peripheral system. So, although the drugs looked like they worked in the lab, when they moved to clinical trials, they failed."

Substance P works in the peripheral system by modulating the action of certain proteins that control the ability of pain-sensing neurons to respond to 'painful' stimuli. In particular, Substance P makes one type of these proteins extremely sensitive to zinc, so that natural trace levels of zinc in circulation are enough to dampen their activity and suppress the neuronal responses.

Professor Gamper - who is also a visiting professor at Hebei Medical University - believes this discovery could open the door to new drugs that don't have the negative side effects currently associated with stronger painkillers.

"Drugs like morphine hijack the body's natural painkilling mechanisms, such as those used by endorphins, but because they act within the central nervous system, they can affect other brain cells that use similar pathways, leading to side effects such as addiction or sleepiness," says Professor Gamper. "If we could develop a drug to mimic the mechanism that Substance P uses, and ensured it couldn't pass the into the CNS, so was only active within the peripheral , it's likely it could suppress pain with limited side effects."

The study - which looked at the action of Substance P within in the lab and in animal models - focused on , but Professor Gamper aims to look at its role within chronic as well.

Explore further: Researchers reveal different mechanisms of pain

More information: Dongyang Huang et al, Redox-Dependent Modulation of T-Type CaChannels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P, Antioxidants & Redox Signaling (2016). DOI: 10.1089/ars.2015.6560

Related Stories

Researchers reveal different mechanisms of pain

May 14, 2012
Researchers at the University of Leeds have found a previously unknown mechanism through which pain is signalled by nerve cells – a discovery that could explain the current failings in the drug development process for ...

New findings point to central nervous system role in painful diabetic peripheral nerve disease

January 27, 2016
Emerging evidence suggests that the central nervous system (CNS) is a key contributor to the problem of painful peripheral nerve disease in people with diabetes, according to a special article in the February issue of Pain, ...

Scientists turn blood into neural cells

May 21, 2015
Scientists at McMaster University have discovered how to make adult sensory neurons from human patients simply by having them roll up their sleeve and providing a blood sample.

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 ...

Narcotic painkillers prolong pain in rats, study finds

May 30, 2016
The dark side of painkillers - their dramatic increase in use and ability to trigger abuse, addiction and thousands of fatal overdoses annually in the United States is in the news virtually every day.

Recommended for you

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

New technique overcomes genetic cause of infertility

August 17, 2017
Scientists have created healthy offspring from genetically infertile male mice, offering a potential new approach to tackling a common genetic cause of human infertility.

Inhibiting a protein found to reduce progression of Alzheimer's and ALS in mice

August 17, 2017
(Medical Xpress)—A team of researchers with Genetech Inc. and universities in Hamburg and San Francisco has found that inhibiting the creation of a protein leads to a reduction in the progression of Alzheimer's disease ...

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

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.