fight-or-flight response

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

Stress can impair memory, reduce brain size in middle age

October 25, 2018

Science Daily/University of Texas Health Science Center at San Antonio

Stress may be causing impaired memory and brain shrinkage in middle-age adults, even before symptoms of Alzheimer's or other dementia begin, according to a new study.

 

Adults in their 40s and 50s with higher levels of cortisol -- a hormone linked to stress -- performed worse on memory and other cognitive tasks than peers of the same age with average cortisol levels, research found. Higher cortisol in the blood also was associated with smaller brain volumes, according to the study, published Oct. 24 in Neurology, the medical journal of the American Academy of Neurology.

 

"In our quest to understand cognitive aging, one of the factors attracting significant interest and concern is the increasing stress of modern life," said study senior author Sudha Seshadri, M.D., professor of neurology at UT Health San Antonio and founding director of the university's Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases. "One of the things we know in animals is that stress can lead to cognitive decline. In this study, higher morning cortisol levels in a large sample of people were associated with worse brain structure and cognition."

 

The cognitive data are from 2,231 participants in the Framingham Heart Study, for which Dr. Seshadri is a senior investigator; 2,018 participants also underwent magnetic resonance imaging (MRI) to measure brain volume. The team included Framingham collaborators at Harvard Medical School; the National Heart, Lung, and Blood Institute; Boston University School of Medicine; the University of California, Davis, at Sacramento; and UT Health San Antonio.

 

Blood serum cortisol, which varies in level throughout the day, was measured in early morning (between 7:30 and 9 a.m.) in each fasting participant. The study featured a relatively young sample of male and female participants (mean age 48.5).

 

"Cortisol affects many different functions, so it is important to fully investigate how high levels of the hormone may affect the brain," said study lead author Justin B. Echouffo-Tcheugui, M.D., Ph.D., of Harvard Medical School. "While other studies have examined cortisol and memory, we believe our large, community-based study is the first to explore, in middle-aged people, fasting blood cortisol levels and brain volume, as well as memory and thinking skills."

 

Memory loss and brain shrinkage were found in the study's middle-age participants before the onset of any symptoms, Dr. Echouffo-Tcheugui noted. He said it is important for physicians to counsel people with higher cortisol levels on ways to reduce stress, such as getting enough sleep and engaging in moderate exercise.

 

"The faster pace of life today probably means more stress, and when we are stressed, cortisol levels increase because that is our fight-or-flight response," Dr. Seshadri said. "When we are afraid, when we are threatened in any way, our cortisol levels go up. This study adds to the prevailing wisdom that it's never too early to be mindful of reducing stress."

 

Findings were adjusted for factors including age, sex, smoking and body mass index. The team asked whether having APOE4, a genetic risk factor for cardiovascular disease and Alzheimer's disease, might be associated with higher cortisol level. This did not prove to be the case.

https://www.sciencedaily.com/releases/2018/10/181025084043.htm

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