Research goal: Noninvasive therapy for chronic pain

Chronic pain is a major public health challenge.

According to the Centers for Disease Control, 1 in 4 adults experienced chronic pain in 2023. Of those, almost one in 10 had pain severe enough to limit them in life or work.

Gabriel Isaac, a neuroscience doctoral student conducting research at the Fralin Biomedical Research Institute at VTC, is working to develop safe, effective treatments for chronic pain — without the need for surgery.

“We can’t treat what we can’t reach — and unfortunately, these deep pain neuronal circuits remain out of range for most existing therapies,” Isaac said.

Isaac is this year’s recipient of the Jeanine L. Matte Fellowship through the Fralin Biomedical Research Institute at VTC. The fellowship will support his research with Wynn Legon, assistant professor at the institute who studies the use of low-intensity focused ultrasound, or LIFU, to treat addiction, chronic pain, and mental health indications including anxiety.

LIFU sends acoustic energy deep in the brain with high spatial resolution; numerous studies have shown that it can reduce the subjective experience of pain. But human studies have been inconsistent. “LIFU risks remaining a laboratory curiosity rather than evolving into a viable therapeutic intervention,” Isaac said.

Isaac was inspired to pursue health research after witnessing firsthand the downstream effects of chronic illnesses on family members’ mental and physical health. It became even more present when his grandmother was diagnosed with dementia and moved from Puerto Rico to live with his family in Tennessee. “Seeing her decline and the effect of her illness on my family was a huge influence,” he said. “As a high schooler I was like, ‘Alright, I’m going to go fix that.’”

As an undergraduate student at the University of Tennessee he pursued a dual degree in biomedical engineering and neuroscience. Like others before him, he found out the brain is a complex organ.

He studied the effect of heavy metal contamination on zebrafish behavior and neurophysiology. In a research internship with Professor Warren Bickel at the Fralin Biomedical Research Institute, he built a custom-analysis pipeline for behavioral datasets related to substance use. Back in Tennessee, he analyzed the impact of fentanyl on neural activity in rodent models in the lab of Professor Ralph Lydic.

In Legon’s lab, he was inspired by the direct line between moving research findings from the lab into clinical practice. For his research project, Isaac is working to determine how different focused ultrasound intensities, durations, and pulsing parameters interact in the human brain.

“This work tackles a major public health challenge — chronic pain — by advancing a breakthrough brain stimulation technique into a safe, noninvasive treatment,” Isaac said. The fellowship will support experiments that can move the technology toward clinical relief.

“Gabriel is driven by a clear translational vision of transforming LIFU from an intriguing technology into a dependable therapeutic tool,” said Legon, who also holds an appointment in the School of Neuroscience in the College of Science. “His work combines methodological rigor with a deep commitment to clinical relevance, positioning him as a future leader in noninvasive neuromodulation.”

Through his experiences in Legon’s lab, Isaac’s been inspired by a different type of translational science. “As a biomedical engineering undergrad, you want to make medical devices that are complicated and have so many moving parts,” he said. “Sometimes in health, the simplest things stand the test of time, when you can immediately accomplish a therapeutic result.”

Isaac plans to use functional MRI (fMRI), a neuroimaging tool, to personalize the therapy. Focused ultrasound will target each research participant’s unique brain network, which will be identified through scans collected during a task-based fMRI. The fellowship will support the collection of the scans used for individualized targeting and allow him to share his findings with other researchers with expertise in neuromodulation and neuroimaging. The lab is still recruiting participants for the research.

The fellowship is made possible because of gift from Matte ’71. The award prioritizes novel approaches to unsolved questions in neuroscience research, particularly those that accelerate the pace of brain research and its translation to public health applications.