Nav: Home

Researchers devise decoy molecule to block pain where it starts

January 16, 2018

For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

"If you have ever hit yourself with a hammer, afterward, even a light touch can be painful for days or even weeks," said Campbell, who researches pain on the molecular level at The University of Texas at Dallas. "While many of us may not be coordinated enough to avoid an accident, my goal is to disrupt the inception and persistence of pain memories."

Campbell directs the Laboratory of RNA Control and recently published a study in the journal Nature Communications in close collaboration with Dr. Ted Price, an associate professor from the Pain Neurobiology Research Group, and Dr. Michael Burton, a new assistant professor from the School of Behavioral and Brain Sciences who conducted postdoctoral work at UT Dallas.

This work describes a new method of reducing pain-associated behaviors with RNA-based medicine, creating a new class of decoy molecules that prevent the onset of pain.

"Even simple memories are nothing short of extraordinary," Campbell said. "To promote healing, our nervous system catalogs our sensory experiences and, under normal circumstances, eventually forgets. Defects in this process can result in chronic pain -- a root cause of enormous suffering."

Reducing Behavioral Response to Pain

The need for research in this field is easy to understand.

"Pain is a pervasive and devastating problem," Campbell said. "It's the most prominent reason why Americans seek medical attention. Poorly treated pain causes enormous human suffering, as well as a tremendous burden on medical care systems and our society."

Campbell's team took the approach of blocking the creation of the proteins that set pain in motion. After an injury, instructions provided by the genome -- the full set of genetic instructions present in each cell -- are translated to create pain-signaling proteins. Those instructions are encoded in molecules called messenger RNA, or mRNA. The decoy Campbell's team constructed interrupts the pain-protein synthesis process that mRNA facilitates, reducing signs of inflammation and impairing pain behaviors.

"When you have an injury, certain molecules are made rapidly," said Campbell, an assistant professor in the Department of Biological Sciences in the School of Natural Sciences and Mathematics. "With this Achilles' heel in mind, we set out to sabotage the normal series of events that produce pain at the site of an injury. In essence, we eliminate the potential for a pathological pain state to emerge."

The RNA mimic that Campbell's team designed was injected at the site of an injury in experiments on mice, and showed the ability to reduce behavioral response to pain.

"We're manipulating one step of protein synthesis," Campbell said. "Our results indicate that local treatment with the decoy can prevent pain and inflammation brought about by a tissue injury."

Overcoming a Molecular Challenge

One huge hurdle in creating such an RNA-based compound was overcoming the rapid metabolism of these molecules.

"Molecules that degrade quickly in cells are not great drug candidates. The stability of our compounds is an order of magnitude greater than unmodified RNA." Campbell said.

Campbell explained that specialized nerve cells called nociceptors communicate with your brain in response to thermal, chemical and mechanical stimuli.

"Imagine touching a hot stovetop, walking into a wall or getting a paper cut," he said. "Part of the cellular origin that causes subsequent pain is initiated by nociceptors, but the molecular mechanisms behind these persistent changes are poorly understood. Our study developed a targeted inhibitor that both shed light on these processes and reduced pain sensitization following an injury."

Campbell emphasized the importance of treating pain at the site of an injury; a major problem with drugs that interact with the central nervous system is that they also can affect the reward center of the brain.

"The ongoing opioid crisis highlights the need for pain treatments that don't create addictions," he said. "Hopefully, this is a step in that direction."

Campbell credits the role of team-based science for the discovery.

"This work was made possible through a tight collaboration between my lab and that of Dr. Price," Campbell said. "These experiments would not have been possible without Ted's tremendous support, dedication and broadly insightful character. Ted is an eminent scholar at the interface of translational control and pain. His deep expertise in pain mechanisms permeates the manuscript.

"I feel incredibly fortunate to benefit from outstanding collaborators here at UT Dallas, which has emerged as a key player on the national stage of pain research," said Campbell, who arrived at the University in 2015.

This study was supported by a $2 million, five-year grant from the National Institutes of Health to study RNA-binding proteins in peripheral neurons. Price and Dr. Joseph Pancrazio, a professor in the Department of Bioengineering in the Erik Jonsson School of Engineering and Computer Science, are collaborators on the grant.

Campbell believes this effort proposes a new method of treating a broad range of medical issues.

"To the best of our knowledge, this is the first attempt to create a chemically stabilized mimic to competitively inhibit RNA to disrupt RNA-protein interactions," he said. "Our approach suggests that targeting those interactions may provide a new source of pharmacological agents. This proof of concept allows us to open a whole new area of science by virtue of the route that we're attacking it."
Other authors of the Nature Communications paper are: lead author and National Council on Science and Technology-supported postdoctoral scholar Dr. Paulino Barragán-Iglesias, a scientist in the School of Behavioral and Brain Sciences; staff scientist Tzu-Fang Lou; postdoctoral scholar Dr. Salim Megat; and Vandita D. Bhat, a doctoral student in biological sciences.

University of Texas at Dallas

Related Pain Articles:

Pain researchers get a common language to describe pain
Pain researchers around the world have agreed to classify pain in the mouth, jaw and face according to the same system.
It's not just a pain in the head -- facial pain can be a symptom of headaches too
A new study finds that up to 10% of people with headaches also have facial pain.
New opioid speeds up recovery without increasing pain sensitivity or risk of chronic pain
A new type of non-addictive opioid developed by researchers at Tulane University and the Southeast Louisiana Veterans Health Care System accelerates recovery time from pain compared to morphine without increasing pain sensitivity, according to a new study published in the Journal of Neuroinflammation.
The insular cortex processes pain and drives learning from pain
Neuroscientists at EPFL have discovered an area of the brain, the insular cortex, that processes painful experiences and thereby drives learning from aversive events.
Pain, pain go away: new tools improve students' experience of school-based vaccines
Researchers at the University of Toronto and The Hospital for Sick Children (SickKids) have teamed up with educators, public health practitioners and grade seven students in Ontario to develop and implement a new approach to delivering school-based vaccines that improves student experience.
Pain sensitization increases risk of persistent knee pain
Becoming more sensitive to pain, or pain sensitization, is an important risk factor for developing persistent knee pain in osteoarthritis (OA), according to a new study by researchers from the Université de Montréal (UdeM) School of Rehabilitation and Hôpital Maisonneuve Rosemont Research Centre (CRHMR) in collaboration with researchers at Boston University School of Medicine (BUSM).
Becoming more sensitive to pain increases the risk of knee pain not going away
A new study by researchers in Montreal and Boston looks at the role that pain plays in osteoarthritis, a disease that affects over 300 million adults worldwide.
Pain disruption therapy treats source of chronic back pain
People with treatment-resistant back pain may get significant and lasting relief with dorsal root ganglion (DRG) stimulation therapy, an innovative treatment that short-circuits pain, suggests a study presented at the ANESTHESIOLOGY® 2018 annual meeting.
Sugar pills relieve pain for chronic pain patients
Someday doctors may prescribe sugar pills for certain chronic pain patients based on their brain anatomy and psychology.
Peripheral nerve block provides some with long-lasting pain relief for severe facial pain
A new study has shown that use of peripheral nerve blocks in the treatment of Trigeminal Neuralgia (TGN) may produce long-term pain relief.
More Pain News and Pain Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

How to Win Friends and Influence Baboons
Baboon troops. We all know they're hierarchical. There's the big brutish alpha male who rules with a hairy iron fist, and then there's everybody else. Which is what Meg Crofoot thought too, before she used GPS collars to track the movements of a troop of baboons for a whole month. What she and her team learned from this data gave them a whole new understanding of baboon troop dynamics, and, moment to moment, who really has the power.  This episode was reported and produced by Annie McEwen. Support Radiolab by becoming a member today at