New Research on Chronic Pain Management
Summary: Millions suffer from chronic pain, and while opioids have been a common treatment, they carry risks of addiction and side effects. Researchers have identified specific neurons in the amygdala that heighten the unpleasant sensation of pain, paving the way for new medications that could alleviate discomfort without dulling normal sensations.
With a significant $12 million grant from the NIH, scientists are working on developing small molecules that can safely target these neurons. Though this research is still in its early stages, it holds the potential to change how chronic pain is treated and lessen the dependency on opioids.
Key Facts
- Target Identified: Neurons in the amygdala are linked to the emotional distress of pain.
- Non-Opioid Strategy: New drug options aim to block the unpleasant feelings of pain while keeping normal sensation intact.
- Major Support: A $12 million NIH grant backs the early development of this strategy.
Chronic pain affects countless individuals, often leading to profound disruptions in daily life. Matt Mauck, an anesthesiologist and pain specialist at the UNC Hospitals Pain Management Center, witnesses this struggle firsthand.
“Chronic pain influences quality of life, impacts relationships, and can even affect sleep and mood,” Mauck noted. “We really need better therapies for these patients.”
Pain management typically involves a variety of treatment methods, like medications, therapies, injections, and specialized procedures, to help patients regain control over their pain. But these approaches sometimes fall short of what patients need.
Opioids, such as oxycodone and tramadol, can be effective, especially in the short term, but their long-term use can lead to tolerance, addiction, and other complications.
Researchers like Gregory Scherrer are committed to finding new pain relief methods that mitigate addiction risks. With the recent NIH funding, the team aims to transform their foundational scientific discoveries into applicable solutions.
“Pain is intrinsically unpleasant,” Scherrer explained. “We are working on various drug candidates that could selectively target specific neurons in the brain to reduce the unpleasantness of pain while preserving the ability to sense bodily issues.”
The Role of Pain
Pain serves as a critical warning, letting us know when something might be harming our body. When a painful stimulus is detected, the information travels through nerves to the spinal cord and up to the brain, where the emotional experience of pain is created. This alerting system encourages us to avoid harmful situations—like removing a hand from a hot stove.
However, in chronic pain conditions—where discomfort persists for six months or longer—the sensation lingers even after the initial injury has healed.
Pharmaceutical companies have long sought to develop effective treatments for chronic pain, yet they’ve encountered many challenges and side effects. Opioids, used for centuries, work by binding to specific brain receptors, offering pain relief and a sense of euphoria.
“The tricky part is that some pain treatments, like local anesthetics, can block all sensation, while opioids activate reward pathways in the brain, potentially leading to dependence,” Scherrer noted.
A New Target in Pain Management
To better manage pain with fewer side effects, Scherrer has focused on understanding how our nervous system perceives pain and relief. For years, researchers struggled to identify which neurons contribute to the unpleasant nature of pain.
“We suspected that finding these cells could offer a novel treatment for pain,” Scherrer said. “By addressing these cells, we could reduce the unpleasantness of chronic pain while still allowing patients to feel their body’s signals.”
After extensive research, Scherrer identified these crucial neurons. A 2019 study published in Science confirmed that they are located in the amygdala, a small region of the brain that plays a role in emotional reactions to pain.
Using a miniature microscope on the heads of mouse models, researchers monitored which neurons activated in response to pain. Out of thousands, one particular group was consistently activated.
Following his 2019 breakthrough, Scherrer aimed to identify specific receptors in these neurons that could serve as targets for drug-like compounds. Using funding from the NIH’s HEAL Initiative, he isolated these neurons and employed RNA sequencing to discover potential drug targets.
Entering Preclinical Development
In March, Scherrer’s project earned a $12 million U19 grant from the NIH, fostering further exploration. This prestigious grant supports collaborative efforts to tackle significant scientific and public health challenges.
Now, researchers from the UNC School of Medicine, Stanford University, and the University of California, San Francisco are developing small molecules designed to activate receptors in both mouse models and human amygdalae.
In collaboration with medicinal chemist Jeff Aubé and therapeutic drug discovery expert Bryan Roth, Scherrer is making strides toward developing new pain management options. Although clinical trials are still a way off, the goal is to create a pain relief drug.
“We aim to finalize a candidate and submit an Investigational New Drug application with the FDA to start clinical trials in the next five years or so,” Scherrer stated.
