PIEZO2, a molecular target for treating clinical pain

October 10, 2018, The Scripps Research Institute
Left to right: Swetha Murthy and Ardem Patapoutian led the study at Scripps Research. Credit: Scripps Research

If you've ever been sunburned, you've experienced the dreaded pain of putting on a shirt the next day. Fabric that should feel soft turns into a layer of painful pressure. That kind of pain-from what should feel like a gentle touch-is called allodynia, and it's a fact of life for many people who suffer from chronic conditions, such as fibromyalgia or nerve damage from chemotherapy. There are limited options to help these patients.

Now scientists at Scripps Research have identified the molecule in neurons responsible for tactile allodynia, a protein called PIEZO2. It was originally discovered in the lab of Ardem Patapoutian, Ph.D., who led the work to determine its role in allodynia in .

The new Scripps Research study was published this week in the journal Science Translational Medicine alongside a study led by the National Institutes of Health that showed Piezo2 is also responsible for allodynia in humans.

"These two studies provide validation that targeting PIEZO2 could be beneficial in the clinic," says Patapoutian, professor at Scripps Research and investigator with the Howard Hughes Medical Institute.

"We hope that these results will help researchers develop better treatments for managing this common form of pain," says Alexander T. Chesler, Ph.D., a Stadtman Investigator at the NIH's National Center for Complementary and Integrative Health (NCCIH) and study author of the study in humans.

For both studies, the researchers induced allodynia using various methods including application of capsaicin, the irritating molecule active in chili peppers, to areas of the skin. Capsaicin is known to sensitize neurons, causing inflammation similar to a sunburn.

Swetha Murthy, Ph.D., first author of the Scripps Research study, looked at how mice reacted to gentle touch after they were exposed to capsaicin. While normal mice experienced allodynia, the mice with PIEZO2 "knocked out" did not react. The same held true when Chesler tested humans with mutations that inactivated their PIEZO2.

"It was very gratifying to see this in both studies," says Murthy. "It usually takes years to confirm if results observed in mice hold true in humans, so I think it was mutually exciting for both groups."

Going forward, the researchers want to understand exactly how inflammation interferes with normal touch signals. They are also interested in identifying small molecules that block PIEZO2. Topical application of such PIEZO2 blockers could be beneficial for patients suffering from neuropathic pain.

Explore further: Genetic study paves way for new neuropathic pain treatments

More information: Swetha E. Murthy et al, The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice, Science Translational Medicine (2018). DOI: 10.1126/scitranslmed.aat9897

M. Szczot el al., "PIEZO2 mediates injury-induced tactile pain in mice and humans," Science Translational Medicine (2018). stm.sciencemag.org/lookup/doi/ … scitranslmed.aat9892

Related Stories

Genetic study paves way for new neuropathic pain treatments

February 22, 2018
A pioneering, multi-institutional research group has conducted an in-depth analysis of the molecular differences between the most common symptoms associated with neuropathic pain. The project may pave the way for the development ...

Scientists provide new grasp of soft touch

April 6, 2014
A study led by scientists at The Scripps Research Institute (TSRI) has helped solve a long-standing mystery about the sense of touch.

Study finds long-sought protein sensor for the 'sixth sense'—proprioception

November 9, 2015
Can you touch a finger to the tip of your nose with your eyes closed? Most of us can, thanks to a sense called proprioception, which tells us where our body parts are relative to each other and our environment. Not surprisingly, ...

'Sixth sense' may be more than just a feeling

September 22, 2016
With the help of two young patients with a unique neurological disorder, an initial study by scientists at the National Institutes of Health suggests that a gene called PIEZO2 controls specific aspects of human touch and ...

Scientists identify principal protein sensor for touch

December 3, 2014
A team led by biologists at The Scripps Research Institute (TSRI) has solved a long-standing mystery in neuroscience by identifying the "mechanoreceptor" protein that mediates the sense of touch in mammals.

Fighting pain through knowledge about sensory organs in the fingertips

October 12, 2016
That a finger can distinguish the texture of satin from suede is an exquisite sensory discrimination largely relying on small sensory organs in the fingertips called Merkel discs. Jianguo Gu, Ph.D., of the University of Alabama ...

Recommended for you

Research shows signalling mechanism in the brain shapes social aggression

October 19, 2018
Duke-NUS researchers have discovered that a growth factor protein, called brain-derived neurotrophic factor (BDNF), and its receptor, tropomyosin receptor kinase B (TrkB) affects social dominance in mice. The research has ...

Good spatial memory? You're likely to be good at identifying smells too

October 19, 2018
People who have better spatial memory are also better at identifying odors, according to a study published this week in Nature Communications. The study builds on a recent theory that the main reason that a sense of smell ...

How clutch molecules enable neuron migration

October 19, 2018
The brain can discriminate over 1 trillion odors. Once entering the nose, odor-related molecules activate olfactory neurons. Neuron signals first accumulate at the olfactory bulb before being passed on to activate the appropriate ...

Scientists discover the region of the brain that registers excitement over a preferred food option

October 19, 2018
At holiday buffets and potlucks, people make quick calculations about which dishes to try and how much to take of each. Johns Hopkins University neuroscientists have found a brain region that appears to be strongly connected ...

Gene plays critical role in noise-induced deafness

October 19, 2018
In experiments using mice, a team of UC San Francisco researchers has discovered a gene that plays an essential role in noise-induced deafness. Remarkably, by administering an experimental chemical—identified in a separate ...

Brain cells called astrocytes have unexpected role in brain 'plasticity'

October 18, 2018
When we're born, our brains have a great deal of flexibility. Having this flexibility to grow and change gives the immature brain the ability to adapt to new experiences and organize its interconnecting web of neural circuits. ...

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.