OU researchers explore vagus nerve stimulation for multiple conditions

OKLAHOMA CITY AND TULSA – The vagus nerve, which takes a long, winding path from the brain to the large intestine and branches out to several organs along the way, is increasingly viewed as a potential key to the treatment of multiple medical and mental health conditions.

The vagus nerve controls body functions such as digestion, heart rate and the immune system by sending signals telling the body how to operate. By stimulating the vagus nerve with electrical impulses, University of Oklahoma researchers are achieving promising results in their studies for the treatment of musculoskeletal diseases like osteoarthritis, major depression, and heart conditions such as postural tachycardia syndrome and atrial fibrillation.

Osteoarthritis

Osteoarthritis (OA) is the most common form of arthritis, affecting more than 500 million people worldwide. Despite its prevalence, therapies are limited. There are no drugs to slow the progression of OA, and although there are treatments for pain, many have side effects that limit their long-term use.

Stimulating the vagus nerve through a simple clip on the ear may hold the key to improving quality of life. Rheumatologist and OU College of Medicine Professor Mary Beth Humphrey, M.D., Ph.D., has studied the approach in mice and is developing a clinical trial that she plans to begin next year.

In two different models of OA in the knee (ACL rupture and destabilized medial meniscus), Humphrey’s team discovered that vagus nerve stimulation decreased pain and limited the progression of OA in mice.

Specifically, she found that vagus nerve stimulation decreased central pain sensitization, which, in humans, is pain in the joint that causes a person to feel pain all over. Interestingly, female mice primarily saw this improvement. However, vagus nerve stimulation limited the progression of OA in both male and female mice.

“It’s very exciting to think that this may work for the treatment of OA,” said Humphrey, who primarily sees patients at the VA in Oklahoma City. “Veterans have more OA than those who have not served in the military. And veterans get OA much earlier in life, which means they need a knee replacement much earlier. If we had a way to help our patients feel better without the side effects of pain medication, and to delay the need for a knee replacement, that would be exciting.”

Treatment-resistant depression

Sometimes called a “pacemaker for the brain,” vagus nerve stimulation therapy is approved by the Food and Drug Administration for the treatment of several types of depression, and clinical trials continue to study its effectiveness for improving mental health. At the OU School of Community Medicine in Tulsa, psychiatry faculty members are offering a trial studying an implanted vagus nerve device for its potential to alleviate depression symptoms in patients who have not been successfully treated with other therapies. Sponsored by the company LivaNova, the trial is for adults with treatment-resistant major depressive disorder and bipolar depression.

In the trial, a surgeon implants the VNS Therapy™ device just under the skin on the left side of the chest below the collarbone, and a small wire coming out of the device is then attached to the left vagus nerve in the neck. An electrode passes stimulation to the vagus nerve, which, in turn, sends electrical impulses to areas of the brain associated with mood regulation. Psychiatry faculty members regulate the device settings, which can be adjusted as needed.

The study is double-blinded, meaning that neither the study participants nor the investigators know whether the device is actually turned on. After participants have been in the study for a year, the ones who received the placebo stimulation have their devices turned on. The trial is ongoing, and all participants’ psychiatric symptoms are evaluated over a five-year period.

Although there are many treatments for depression, some patients don’t respond to traditional options. Studying a new treatment option like vagus nerve stimulation is gratifying, said Ondria Gleason, M.D., professor and chair of the Department of Psychiatry at the OU School of Community Medicine, who is leading the trial for OU.

“Treating depression is so important because it affects not just mental health, but physical health and social health,” she said. “If you can make a difference in someone’s mental health, you can make a difference in the totality of their life.”

Cardiac conditions

Millions of people suffer from postural tachycardia syndrome (POTS), and the condition has increased significantly since the arrival of COVID-19 because the virus can affect the heart. People with POTS experience symptoms like dizziness and heart palpitations every time they stand up after they’ve been sitting or lying down.

Stavros Stavrakis, M.D., Ph.D., a professor of cardiology in the OU College of Medicine, has conducted studies showing that stimulating the vagus nerve through a clip on the ear significantly lessens the woozy symptoms of POTS.

In one study, published in JACC: Clinical Electrophysiology, patients’ heart rates still increased upon standing, but not as much – 15 beats less per minute than without the stimulation. In addition, the research team discovered that the stimulation decreased the surge of adrenaline in the body and the level of inflammation in the blood, which also contribute to POTS.

“There is a lot of excitement about vagus nerve stimulation in the field of cardiology,” Stavrakis said. “It is non-invasive and inexpensive, and it doesn’t have side effects the way that medication would. I’m optimistic that it will become a treatment that can help improve the quality of life for people with POTS.”

Stavrakis has also studied vagus nerve stimulation for atrial fibrillation (an irregular heartbeat), discovering that it decreased atrial fibrillation by 85% when patients were monitored, compared to those who didn’t receive the treatment. He is now conducting larger clinical studies for both POTS and atrial fibrillation to better understand how the treatment works, which patients are best suited for the treatment, and how long its benefits last.

Vagus nerve stimulation is somewhat unusual in a complex medical field like cardiology, but its promise is its ease of use and affordability. Stavrakis envisions a future where people with conditions like POTS could wear a wireless stimulation device resembling an ear pod.

“With advancements in technology, people could be listening to music on their phone while also stimulating their vagus nerve,” he said. “We’re not there yet, but I think it’s the way of the future.”

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About the University of Oklahoma

Founded in 1890, the University of Oklahoma is a public research university with campuses in Norman, Oklahoma City and Tulsa. As the state’s flagship university, OU serves the educational, cultural, economic and health care needs of the state, region and nation. In Oklahoma City, OU Health Sciences is one of the nation’s few academic health centers with seven health profession colleges located on the same campus. OU Health Sciences serves approximately 4,000 students in more than 70 undergraduate and graduate degree programs spanning Oklahoma City and Tulsa and is the leading research institution in Oklahoma. For more information about OU Health Sciences, visit www.ouhsc.edu.