A nonaddictive painkiller is on the horizon
Scientists at Carolina have focused research on a drug that targets the “unpleasantness” the brain associates with pain.
Pain management providers use a combination of evidence-based treatment options: medications, therapy, injections and specialized procedures. But these therapies are sometimes not enough to control the pain. Opioid medications, like oxycodone and tramadol, can help in the short term, but long-term use can be problematic, complicated by tolerance and addiction.
Researchers in the UNC School of Medicine and UNC Eshelman School of Pharmacy are determined to create a new pain medication that can offer relief to those in need — without the addictive properties. Now supported by a multimillion-dollar grant from the National Institutes of Health, the research team is converting their basic science findings into clinically relevant results.
“The fundamental problem is that pain is unpleasant,” said Gregory Scherrer, an associate professor in the medical school’s cell biology and physiology and pharmacology departments and the UNC Neuroscience Center. “We are currently working on several drug candidates that can target specific neurons in the brain and turn off the ‘unpleasantness’ of pain, while maintaining sensation in the body.”
The purpose of pain
Pain serves as a warning signal to our bodies, alerting us that something is actually or potentially harming the body’s tissues.
When neurons first sense a painful stimulus, the nerves relay that information through the spinal cord to the brain. From there, the pain becomes a conscious, emotional experience. This painful, negative signal motivates us to avoid whatever is causing pain — to remove our hand from a hot stove or to mend a bone fracture.
Treatment can get tricky, Scherrer said, especially when the pain is chronic, lasting for six months or longer after an injury. Local anesthetics, for example, prevent a patient from feeling any sensation at all, while opiates and opioids can lead to dependence or withdrawal symptoms once the therapy is stopped.
A new way to target pain
To reduce suffering pain more efficiently and reduce side effects, Scherrer has focused his research on the nervous system and how it perceives pain and pain relief. He was looking for a way for chronic pain patients to experience enough pain to sense a problem without its being unpleasant.
After years of research, Scherrer was able to pinpoint the exact brain cells responsible for making pain unpleasant. They are located in the amygdala, a peanut-sized area of the brain that regulates emotional responses to pain and fear, as revealed in a 2019 study in Science that Scherrer co-authored.
Scherrer needed to know what receptors within these cells could serve as docking stations for a drug-like molecule. With funding from the NIH’s Helping to End Addiction Long-term initiative, he isolated these neurons and identified these docking sites and small molecules for these receptors.
Preclinical development stage
In March, Scherrer received a prestigious, multiyear cooperative award of $12 million from the NIH to further his research.
Experts from the UNC School of Medicine, Stanford University and the University of California, San Francisco, are now developing a small molecule with drug-like properties that can activate receptors in mouse models and the human amygdala.
Jeff Aubé, a medicinal chemist at the UNC Eshelman School of Pharmacy, and Dr. Bryan Roth, an expert on therapeutic drug discovery at the UNC School of Medicine, will be working alongside Scherrer to elevate their research efforts. Although far from clinical trials, the team is closer than ever to creating a new pain drug,
“Our goal over the next five years or more is to develop a pain drug candidate and then to file an Investigational New Drug application with the FDA to begin clinical trials,” said Scherrer.
