3 Ways to Tell Which Vagus Nerve Fibers Are Being Stimulated

Researchers identify how “A, B, & C” vagus nerve fibers respond to stimulation.

Posted Oct 07, 2020

Medically accurate illustration of the vagus nerve
Source: SciePro/Shutterstock

Kevin Tracey is a pioneer of vagus nerve stimulation (VNS) research. Since the early 2000s, his team at The Feinstein Institutes for Medical Research has been rigorously investigating VNS bioelectronic therapies. In 2014, The New York Times did a feature story, "Can the Nervous System Be Hacked?" about Tracey and his decades-long history of potentially game-changing vagus nerve discoveries.

Over the years, I've reported on various findings from the Feinstein Institutes. For example, a few years ago, I wrote a post, "Vagus Nerve Stimulation Dramatically Reduces Inflammation," about a study (Koopman et al., 2016) which found that VNS inhibits cytokine production and reduces the severity of rheumatoid arthritis. Last year, I reported on findings (Addorisio et al., 2019) by other members of Tracey's team who discovered that noninvasive stimulation of the vagus nerve via the outer ear reduces inflammatory responses. (For more on transcutaneous VNS see "Vagus Nerve Stimulation via the Outer Ear Takes Center Stage")

In everyday parlance, the vagus nerve is typically referred to as a singular entity; however, within different branches of the vagus nerve, there are specialized fibers (e.g., "A," "B," and "C" vagal fibers) that each elicit different physiological responses.

This week, Tracey and his team announced that they've just developed a noninvasive way to tell precisely which vagus nerve fibers are being stimulated during VNS by monitoring different physiological markers in lab rats. These findings (Chang et al., 2020) appear in the November-December issue of Brain Stimulation

 Gray's Anatomy (1918)/Public Domain
Plan of upper portions of glossopharyngeal, vagus, and accessory nerves (Gray's Anatomy, Plate 791)
Source: Gray's Anatomy (1918)/Public Domain

For this study, senior author Stavros Zanos and colleagues administered fiber-specific VNS to rats while closely monitoring how stimulation of individual A, B, and C vagal fibers affected breathing, heart rate, and neck muscles. Zanos et al. found that A-fiber vagal stimulation activated muscles in the neck region; B-fiber stimulation mainly triggered fluctuations in heart rate response; C-fiber stimulation caused breathing intervals to change.

Although this research was conducted using an animal model, the researchers plan to investigate if the same physiological markers can be monitored to fine-tune and tailor VNS in humans. "Such models, after calibration in humans, could provide [a] noninvasive estimation of fiber engagement to guide VNS therapy calibration and monitoring," the authors stated. In their open-access paper, they give more details on potential applications of these findings:

"The physiological responses used in our models have all been described in human VNS studies, even though they will certainly be quantitatively different. The A-fiber estimate could be used to minimize off-site effects of VNS like voice alteration, coughing, and paresthesia. Estimation of B-fiber engagement by VNS could facilitate the optimization of stimulation paradigms to treat heart failure or cardiac arrhythmias. Estimation of C-fiber engagement could be used as an index of therapeutic effect in anti-inflammatory applications of VNS."

"To calibrate stimulation parameters, target specific fibers in individual patients and better understand the effects that VNS has on the body, we need to be able to peek into the activity of the vagus nerve and to do so in a noninvasive manner to make it usable in human subjects," Zanos said in an October 1 news release. "Our methods allow us to estimate vagal fiber activity via noninvasive physiological measurements. This will help clinicians tailor neurostimulation therapies in individual patients using these quantitative tools."

"Dr. Zanos' research brings us one step closer to the clinical realization of targeted bioelectronic therapies," Tracey noted. "His work will allow us to better measure and tailor bioelectronic medicine therapies to treat some of the most devastating and common diseases on an individual patient basis."


Yao-Chuan Chang, Marina Cracchiolo, Umair Ahmed, Ibrahim Mughrabi, Arielle Gabalski, Anna Daytz, Loren Rieth, Lance Becker, Timir Datta-Chaudhuri, Yousef Al-Abed, Theodoros P. Zanos, Stavros Zanos. "Quantitative Estimation of Nerve Fiber Engagement by Vagus Nerve Stimulation Using Physiological Markers." Brain Stimulation (First available online: September 18, 2020) DOI: 10.1016/j.brs.2020.09.002

Meghan E. Addorisio, Gavin H. Imperato, Alex F. de Vos, Steve Fort, Richard S. Goldstein, Valentin A. Pavlov, Tom van der Poll, Huan Yang, Betty Diamond, Kevin J. Tracey, and Sangeeta S. Chavan. "Investigational Treatment of Rheumatoid Arthritis with a Vibrotactile Device Applied to the External Ear." Bioelectronic Medicine (First published: April 17, 2019) DOI: 10.1186/s42234-019-0020-4

Frieda A. Koopman, Sangeeta S. Chavan, Sanda Miljko, Simeon Grazio, Sekib Sokolovic, P. Richard Schuurman, Ashesh D. Mehta, Yaakov A. Levine, Michael Faltys, Ralph Zitnik, Kevin J. Tracey, and Paul P. Tak. "Vagus Nerve Stimulation Inhibits Cytokine Production and Attenuates Disease Severity in Rheumatoid Arthritis." Proceedings of the National Academy of Sciences (First published: July 05, 2016) DOI: 10.1073/pnas.1605635113