Researchers at the UNC School of Medicine and UNC Eshelman School of Pharmacy are working on a new pain drug candidate aimed at targeting specific neurons in the brain that control the emotional response to pain. This approach could lead to a non-addictive treatment for chronic pain.
Chronic pain affects many people, impacting their quality of life, relationships, daily activities, and sleep. Matt Mauck, MD, PhD, an anesthesiologist and chronic pain researcher at the UNC Hospitals Pain Management Center, said, “Chronic pain impacts quality of life, relationships, general activity, sleep and so many other essential life functions, and often is accompanied with many symptoms such as fatigue and low mood. Research is needed to develop new therapies to help these patients.”
Current treatments for chronic pain include medications such as opioids. While effective in the short term, opioids can lead to tolerance and addiction over time. Gregory Scherrer, PharmD, PhD, an associate professor at UNC involved in this research effort explained that his team is developing new drug candidates with support from a multi-million U19 grant from the National Institutes of Health (NIH). “The fundamental problem is that pain is unpleasant,” Scherrer said. “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.”
Pain serves as a warning signal for bodily harm. When someone experiences chronic pain—lasting six months or longer—the discomfort persists long after any physical injury has healed. Pharmaceutical companies have tried to address this issue but with limited success due to side effects or risk of addiction associated with traditional opioid medications.
Scherrer noted some challenges: “Where it gets tricky is that some pain management treatments like local anesthetics can prevent you from feeling any sensation at all, painful or otherwise. On the other hand, opioids directly activate reward circuits in the brain and can lead to dependence or withdrawal symptoms once the therapy is stopped.”
Scherrer’s research focuses on understanding how certain neurons contribute to making pain unpleasant. He identified a set of cells within the amygdala responsible for this aspect through studies using mouse models and advanced imaging techniques. In 2019, his work pinpointed these neurons’ role in emotional responses to pain.
With funding from NIH’s HEAL Initiative (Helping to End Addiction Long-term), Scherrer’s team used RNA sequencing techniques to identify receptors on these amygdala neurons as potential targets for new drugs.
A $12 million U19 grant awarded by NIH in March supports ongoing preclinical development work led by experts from UNC School of Medicine alongside Stanford University and University of California San Francisco collaborators. The research team—including Jeff Aubé, PhD (UNC Eshelman School of Pharmacy) and Bryan Roth, MD, PhD (UNC School of Medicine)—is developing small molecules designed to activate these receptors both in animal models and human tissue samples.
Scherrer described next steps: “Our goal over the next five years or more is to develop a pain drug candidate and then to file an Investigational New Drug (IND) application with the FDA to begin clinical trials.”
