The vagus nerve runs from the human brainstem to major peripheral organs and acts as the main conduit for the body’s inflammatory immune response to disease, bacteria and viruses. For the first time, researchers at The Feinstein Institutes for Medical Research have shown the ability to turn on specific receptors in the vagus nerve, activating the inflammatory reflex. The study, published in the journal Molecular Medicine, builds on decades of research into how to control the vagus nerve through electrical stimulation, which is the foundation of bioelectronic medicine.

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Sangeeta Chavan, PhD, is senior author on the Molecular Medicine paper. (Credit: Feinstein Institutes)

The body releases inflammatory proteins to fight disease, which is part of the immune response. The communication pathway, known as the inflammatory reflex, is signaled through the vagus nerve – the longest cranial nerve made up of more than 100,000 individual nerve fibers. Through electrical signals, the brain, via the vagus nerve, can tell the body when to stop releasing inflammatory molecules. If not regulated correctly, the inflammation can be destructive and the root cause of acute and chronic diseases like Crohn’s, rheumatoid arthritis, diabetes and even cancer.

Although the existence of a vagus nerve circuit that protects against excessive inflammation was identified more than 20 years ago, how this response is activated was previously unknown. The new research, led by the Feinstein Institutes’ Sangeeta S. Chavan, PhD, professor in the Institute of Bioelectronic Medicine, identifies a specific subset of sensory neurons on the vagus nerve that sends inflammation-related information to the brain to trigger hypothermia and activates the anti-inflammatory response.

“The vagus nerve is crucial for signaling to the brain and the body’s organs when to turn on or off inflammation – this is our body’s natural response to disease and infection,” said Dr. Chavan, senior author on the paper. “With this new research, we have a better understanding of how to manipulate the vagus nerve’s function through stimulation.”

In the Molecular Medicine paper, titled “Transient Receptor Potential Ankyrin-1-expressing vagus nerve fibers mediate IL-1β induced hypothermia and reflex anti-inflammatory responses,” researchers explain how with the use of light, known as optogenetics, they were able to stimulate the mice’s vagus nerve and record their physiological responses, including body temperature. Scientists studied how Interleukin-1β (IL-1β), a proinflammatory cytokine, interacts with a sensory neuron Transient Receptor Potential Ankyrin-1 (TRPA1). TRPA1, typically a detector of cold, pain and itch, when activated by IL-1β can slow cytokine release, reducing lethal levels of inflammation.

“We continue to learn new mechanisms for vagus nerve control of inflammation,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes, Karches Family Distinguished Chair in Medical Research and co-senior author on the new paper. “These new findings reveal for the first time how the vagus nerve informs the brain about inflammation in the body.”

The Feinstein Institutes is known as the global scientific home of bioelectronic medicine because of early discoveries in its labs. Decades ago, Dr. Tracey and his colleagues discovered the role the vagus nerve plays in controlling our body’s immune response, defining it as the inflammatory reflex. Researchers continue to build off that discovery worldwide to develop devices to cure disease.

About Bioelectronic Medicine

The Feinstein Institutes for Medical Research is the global scientific home of bioelectronic medicine, which combines molecular medicine, neuroscience and biomedical engineering. At the Feinstein Institutes, medical researchers use modern technology to develop new device-based therapies to treat disease and injury.

Built on years of research in molecular mechanisms of disease and the link between the nervous and immune systems, our researchers discover neural targets that can be activated or inhibited with neuromodulation devices, like vagus nerve implants, to control the body’s immune response and inflammation. If inflammation is successfully controlled, diseases – such as arthritis, pulmonary hypertension, Crohn's disease, inflammatory bowel diseases, diabetes, cancer and autoimmune diseases – can be treated more effectively.

Beyond inflammation, using novel brain-computer interfaces, our researchers developed techniques to bypass injuries of the nervous system so that people living with paralysis can regain sensation and use their limbs. By producing bioelectronic medicine knowledge, disease and injury could one day be treated with our own nerves without costly and potentially harmful pharmaceuticals.

About the Feinstein Institutes

The Feinstein Institutes for Medical Research is the home of the research institutes of Northwell Health, the largest health care provider and private employer in New York State. Encompassing 50 research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health system science, and molecular medicine. We make breakthroughs in genetics, oncology, brain research, mental health, autoimmunity, and are the global scientific leader in bioelectronic medicine – a new field of science that has the potential to revolutionize medicine. For more information about how we produce knowledge to cure disease, visit http://feinstein.northwell.edu and follow us on LinkedIn.

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