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 is this connection between mental health and pain that interests Imanuel Lerman, MD, associate professor at the 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 can 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 non-vaginal 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 – may be more susceptible to PTSD," said Lerman. "And so we wanted to know if we could 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 San Diego Healthcare System Veteran Affairs 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 brain of 30 healthy study participants after a painful heat stimulus was applied to their legs. This determines how the body's sympathetic nervous system responds to pain, they also measured the sweat on the skin of the participants before the heat was applied, and at several points as the heat increased.
Half of the patients were treated with noninvasive vagus nervous 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 stimulates the response to heat stimulus in several areas of the brain known to be important for sensory and discriminative pain treatment, as well as in emotional pain centers. The treatment also delayed the pain response in these brain regions – pain-related brain regions were activated 10 seconds later in participants pre-treated with vagus nerve stimulation than in sham-treated patients.
Second, the sweat measurements revealed that vagus nerve stimulation altered autonomic responses to painful heat stimulation. For participants pre-treated with vagus nerve stimulation, the sweat response has 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 nervous stimulation than others to achieve the same outcomes and the necessary frequencies may 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 towards the clinic."
Next, Lerman and colleagues will launch a Veterans Affairs Healthcare-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 or email [email protected]
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. The Food and Drug Administration (FDA) has approved a 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 nervous stimulation can include hoarseness, shortness of breath and nausea.
Co-authors of this study include: Bryan Davis, Linda Sorkin, James Proudfoot, Edward Zhong, Donald Kimball, Ramesh Rao, UC San Diego; Mingxiong Huang, Charles Huang, Andrea Spadoni, Dewleen G. Baker, UC San Diego and the Veterans Affairs San Diego Healthcare System; Bruce Simon, electroCore LLC; and Irina Strigo, Veterans Affairs of the San Francisco Healthcare System.
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