Vagus Nerve and Inflammation

[MomWithOCDSon]

A few of us have discussed the vagus nerve before. This popped up in my FB feed this morning.

 

http://mentalfloss.com/article/65710/9-nervy-facts-about-vagus-nerve

 

[jan251]

Very interesting! A few months ago I came across an article about the neurosurgeon who pioneered work with the vagus nerve.

http://bcm.bc.edu/issues/winter_2016/features/the-generator.html

 

Because nerves communicate by means of electrical signals, the finding raised the possibility that Tracey could dampen TNF production without any drugs at all. He borrowed a handheld nerve stimulator from one of the hospital’s operating rooms and used it to tickle the vagus nerve in several rats. The stimulation suppressed TNF production in the liver and reduced the amount of TNF circulating in the blood.

The discovery, published in Nature in 2000, suggested that the brain acted as a brake on the immune system, and led Tracey to propose what he called “the inflammatory reflex.” During an infection, he theorized, information about the body’s immune response zips up the vagus nerve to the brain. The brain then helps to calibrate this response by sending signals, via the vagus nerve, that curb the production of inflammatory molecules such as TNF. When it works properly, the circuit helps prevent the immune system from spiraling out of control and damaging the body’s own cells and tissues.

Given the dangers that inflammation can pose, it makes sense that this sort of self-regulatory pathway would evolve, says Alejandro Aballay, an immunologist at Duke University, who has identified specific neurons that control the immune response in roundworms. “It’s surprising that it has taken this long for the scientific community to appreciate this neural-immune connection.”

 

http://www.feinsteininstitute.org/our-researchers/kevin-j-tracey-md/

 

The major focus of Dr. Tracey’s laboratory is the molecular basis of inflammation and identifying the mechanism by which neurons control the immune system.

Dr. Tracey participated in the discovery of the direct inflammatory activity of tumor necrosis factor-alpha (TNF) and the therapeutic role of monoclonal anti-TNF. He and his colleagues discovered the role of HMGB1 in inflammation, and identified the molecular mechanisms for signal transduction by signaling through pattern recognition receptors. This provided the first direct evidence to unify mechanisms of inflammation produced by molecules derived from the pathogen and host.

His laboratory discovered the molecular mechanism for the neural control of inflammation, now termed the inflammatory reflex. They delineated the neurophysiological mechanism as dependent upon action potentials transmitted in the vagus nerve, which regulate a T cell subset in spleen that produce acetylcholine. This lymphocyte derived neurotransmitter interacts with alpha-7 nicotinic receptors expressed in macrophages. Signal transduction via this receptor-ligand interaction inhibits cytokine release by suppressing inflammasome activation.

These discoveries enabled Dr. Tracey and his colleagues to develop devices to replace anti-inflammatory drugs. This new field, termed bioelectronic medicine, utilizes electrons delivered to neurons to modulate pathogenic targets in disease. The lead program utilizes devices to stimulate the inflammatory reflex which inhibits TNF in healthy subjects and in patients with rheumatoid arthritis. His lab participated in reporting the first successful clinical trial demonstrating that vagus nerve stimulation can be effective in methotrexate-resistant rheumatoid arthritis patients

 

Edited June 21, 2016 by jan251