Could this ‘decoy molecule’ help to create better drugs for pain?
They believe that what they have discovered about their “decoy molecule” will pave the way for a new class of drugs that prevent pain at the outset without risk of addiction.
A study paper published in the journal Nature Communications describes how the “synthetic RNA mimic reduces pain sensitization in mice” by blocking the creation of pain-signaling proteins.
“We’re manipulating one step of protein synthesis,” explains senior study author Dr. Zachary Campbell, whose laboratory specializes in researching the molecular mechanisms of pain.
“Our results indicate that local treatment with the decoy can prevent pain and inflammation brought about by a tissue injury,” he adds.
Need to tackle the opioid crisis
Around a third of the United States population — which is an estimated 100 million people — is affected by chronic pain, “the primary reason Americans are on disability.”
“Poorly treated pain causes enormous human suffering,” explains Dr. Campbell, “as well as a tremendous burden on medical care systems and our society.”
Another major concern is the rapid rise in prescriptions for opioid pain drugs that has occurred in recent years, which has been accompanied by increases in accidental overdoses as well as hospital admissions for addiction to the medications.
National U.S. survey data that was collected in 2015 shows that nearly 92 million people had used prescription opioids during the previous year. This figure includes around 11.5 million people who “misused” the drugs, the majority of whom said that they had obtained them to relieve pain.
Pain relief that avoids the brain
Opioids are the “most widely used and effective” drugs for treating pain. However, they have a major disadvantage: they interact with areas of the brain that deal with reward and emotion.
The work that Dr. Campbell and his team are doing could lead to pain drugs that do not affect the brain.
They suggest that their study shows that “development of chronic pain requires regulated local protein synthesis” at the site of injury.
The decoy molecule that they have devised acts in molecular mechanisms that involve nociceptors, which are specialized cells at the site of injury that communicate pain signals to the brain.
Following an injury, messenger RNA molecules translate code held in DNA into instructions for making proteins that signal pain.
By mimicking RNA, the decoy molecule interrupts the process that makes the proteins. Injected into the site of injury in mice, it reduced “behavioral response to pain,” say the researchers..
RNA-mimicking molecule slow to degrade
“When you have an injury, certain molecules are made rapidly. With this Achilles’ heel in mind,” says Dr. Campbell, “we set out to sabotage the normal series of events that produce pain at the site of an injury.”
“In essence,” he adds, “we eliminate the potential for a pathological pain state to emerge.” The new molecule that he and his colleagues have devised also overcomes a major challenge of RNA-based medicine: that RNA compounds metabolize very quickly.
“Molecules that degrade quickly in cells are not great drug candidates,” explains Dr. Campbell, adding, “The stability of our compounds is an order of magnitude greater than unmodified RNA.”
He notes that their study is the first to create a “chemically stabilized mimic to competitively inhibit RNA to disrupt RNA-protein interactions.”
He and his team suggest that their findings also improve our understanding of these interactions and open up a completely “new area of science.”