vagus nerve

Stimulating the vagus nerve in the neck might help ease pain associated with PTSD

February 13, 2019

Science Daily/University of California - San Diego

In a randomized, controlled pilot trial, researchers found that participants pre-treated with noninvasive vagus nerve stimulation experienced less pain after heat stimulus than mock-treated participants.

 

Post-traumatic stress disorder, or PTSD, is a mental condition caused by a traumatic event. People with PTSD may experience intrusive memories, negative thoughts, anxiety and chronic pain. The condition is typically treated with a combination of psychotherapy, anti-depressants and anti-anxiety medications.

 

It's this connection between mental health and pain that interests Imanuel Lerman, MD, associate professor at University of California San Diego School of Medicine, Jacobs School of Engineering and Qualcomm Institute, and a pain management specialist at UC San Diego Health and Veterans Affairs San Diego Healthcare System.

 

Lerman especially wants to know how the emotional pain experience may be influenced by the vagus nerve, which runs down both sides of our necks from the brainstem to the abdomen. The vagus nerve also plays a critical role in maintaining heart rate, breathing rate, digestive tract movement and many other basic body functions.

 

In a study published February 13, 2019 in PLOS ONE, Lerman and colleagues tested noninvasive vagus nerve stimulation as a method for dampening the sensation of pain.

 

"It's thought that people with certain differences in how their bodies -- their autonomic and sympathetic nervous systems -- process pain may be more susceptible to PTSD," Lerman said. "And so we wanted to know if we might be able to re-write this 'mis-firing' as a means to manage pain, especially for people with PTSD." Lerman led the study with Alan N. Simmons, PhD, director of the fMRI Research Laboratory at Veterans Affairs San Diego Healthcare System and associate professor of psychiatry at UC San Diego School of Medicine.

 

The team used functional magnetic resonance imaging (fMRI) to get a look at the brains of 30 healthy study participants after a painful heat stimulus was applied to their legs. To determine how the body's sympathetic nervous system responds to pain, they also measured the sweat on the skin of participants before the heat was applied, and at several points as the heat increased.

 

Half the participants were treated with noninvasive vagus nerve stimulation for two minutes -- via electrodes placed on the neck -- approximately 10 minutes before the heat stimulus. The other half received a mock stimulation.

 

Lerman and colleagues report three main findings from this study. First, vagus nerve stimulation blunted peak response to heat stimulus in several areas of the brain known to be important for sensory and discriminative pain processing, as well as in emotional pain centers. The treatment also delayed the pain response in these brain regions -- pain-related brain regions were activated ten seconds later in participants pre-treated with vagus nerve stimulation than in sham-treated participants.

 

Second, the sweat measurements revealed that vagus nerve stimulation altered autonomic responses to painful heat stimulus. For participants pre-treated with vagus nerve stimulation, the sweat response decreased over time, in contrast to the sham-treatment group.

 

Third, vagus nerve stimulation dampened the usual brainstem centers critical for the fight-or-flight-type responses, which are also known to control the sweat response to pain.

 

"Not everyone is the same -- some people may need more vagus nerve stimulation than others to achieve the same outcomes and the necessary frequencies might change over time -- so we'll need to personalize this approach," Lerman said. "But we are hopeful and looking forward to the next steps in moving this approach toward the clinic."

 

Next, Lerman and colleagues will launch a Veterans Affairs Healthcare System-funded clinical trial in San Diego with military veterans, with and without PTSD. They want to determine if at-home vagus nerve stimulation can reduce emotional pain and underlying neural inflammation associated with PTSD. To learn how to participate, please call 858-552-8585.

 

Vagus nerve stimulation is a form of neuromodulation, an approach to pain management that also includes spinal cord and dorsal root ganglion (DRG) stimulation. The U.S. Food and Drug Administration (FDA) has approved noninvasive vagus nerve stimulator for the treatment of episodic and chronic cluster headache and acute migraine, as well as an implantable device for epilepsy. An implanted vagus nerve stimulator is now being tested in a clinical trial for the treatment of rheumatoid arthritis. Side effects of implanted vagus nerve stimulation can include hoarseness, shortness of breath and nausea.

https://www.sciencedaily.com/releases/2019/02/190213142700.htm

Vagus nerve stimulation boosts post-stroke motor skill recovery

March 27, 2018

Science Daily/University of Texas at Dallas

Researchers have demonstrated a method to accelerate motor skill recovery after a stroke by helping the brain reorganize itself more quickly. In a preclinical study, the scientists paired vagus nerve stimulation with a physical therapy task aimed at improving the function of an upper limb in rodents. The results showed a doubled long-term recovery rate relative to current therapy methods.

 

In a preclinical study, the scientists paired vagus nerve stimulation (VNS) with a physical therapy task aimed at improving the function of an upper limb in rodents. The results showed a doubled long-term recovery rate relative to current therapy methods, not only in the targeted task but also in similar muscle movements that were not specifically rehabbed. Their work was recently published in the journal Stroke.

 

A clinical trial to test the technique in humans is underway in Dallas and 15 other sites across the country.

 

Dr. Michael Kilgard, associate director of the Texas Biomedical Device Center (TxBDC) and Margaret Forde Jonsson Professor of Neuroscience in the School of Behavioral and Brain Sciences, led the research team with Dr. Seth Hays, the TxBDC director of preclinical research and assistant professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science, and postdoctoral researcher Eric Meyers PhD'17.

 

"Our experiment was designed to ask this new question: After a stroke, do you have to rehabilitate every single action?" Kilgard said. "If VNS helps you, is it only helping with the exact motion or function you paired with stimulation? What we found was that it also improves similar motor skills as well, and that those results were sustained months beyond the completion of VNS-paired therapy."

 

Kilgard said the results provide an important step toward creating guidelines for standardized usage of VNS for post-stroke therapy.

 

"This study tells us that if we use this approach on complicated motor skills, those improvements can filter down to improve simpler movements," he said.

 

Building Stronger Cell Connections

 

When a stroke occurs, nerve cells in the brain can die due to lack of blood flow. An arm's or a leg's motor skills fail because, though the nerve cells in the limb are fine, there's no longer a connection between them and the brain. Established rehab methods bypass the brain's damaged area and enlist other brain cells to handle the lost functions. However, there aren't many neurons to spare, so the patient has a long-lasting movement deficit.

 

The vagus nerve controls the parasympathetic nervous system, which oversees elements of many unconscious body functions, including digestion and circulation. Electrical stimulation of the nerve is achieved via an implanted device in the neck. Already used in humans to treat depression and epilepsy, VNS is a well-documented technique for fine-tuning brain function.

 

The UT Dallas study's application of VNS strengthens the communication path to the neurons that are taking over for those damaged by stroke. The experiments showed a threefold-to-fivefold increase in engaged neurons when adding VNS to rehab.

 

"We have long hypothesized that VNS is making new connections in the brain, but nothing was known for sure," Hays said. "This is the first evidence that we are driving changes in the brain in animals after brain injury. It's a big step forward in understanding how the therapy works -- this reorganization that we predicted would underlie the benefits of VNS."

 

In anticipation of the technique's eventual use in humans, the team is working on an at-home rehab system targeting the upper limbs.

 

"We've designed a tablet app outlining hand and arm tasks for patients to interact with, delivering VNS as needed," Meyers said. "We can very precisely assess their performance and monitor recovery remotely. This is all doable at home."

 

Expanding the Possibilities for Therapy

 

The researchers are motivated in part by an understanding of the practical limitations of current therapeutic options for patients.

 

"If you have a stroke, you may have a limited time with a therapist," Hays said. "So when we create guidelines for a therapist, we now know to advise doing one complex activity as many times as possible, as opposed to a variety of activities. That was an important finding -- it was exciting that not only do we improve the task that we trained on, but also relatively similar tasks. You are getting generalization to related things, and you're getting sustained improvement months down the line."

 

For stroke patients, the opportunity to benefit from this technology may not be far off.

 

"A clinical trial that started here at UTD is now running nationwide, including at UT Southwestern," Kilgard said. "They are recruiting patients. People in Dallas can enroll now -- which is only fitting, because this work developed here, down to publishing this in a journal of the American Heart Association, which is based here in Dallas. This is a homegrown effort.

 

"The ongoing clinical trial is the last step in getting approved as an established therapy," Kilgard said. "We're hopefully within a year of having this be standard practice for chronic stroke."

https://www.sciencedaily.com/releases/2018/03/180327162606.htm

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