The technique we are going to talk about is called vagus nerve stimulation and it has been used since the 1990s to treat epilepsy and depression.
Nowadays the function of this technique has expanded to the treatment of rheumatoid arthritis and autoimmune disorders that result in the destruction of cartilage around joints and other tissues.
What is surprising is that this vagus-nerve stimulation is the first experiment that links the nervous and the immune systems.
After many studies, the scientist Kevin Tracey has discovered that the major component of this link is the vagus nerve and that the electrical stimulation could represent a better way to treat autoimmune diseases.
In fact, many pharmaceutical companies are running over electroceuticals (devices that regulate nerves) to solve many problems, such as cardiovascular and metabolic diseases. But what Tracey is pointing at is the use of these devices to cure inflammations.
Tracey knows that nerves are not well understood yet, but he relies a lot on these because he thinks that delivering shocks to the vagus nerve, or to other peripheral nerves, can treat a big number of diseases as diabetes, high blood pressure and chronic bleeding.
Chemical aspect
In 1998 Tracey was studying a particular drug called CNI-1493, which was used to cure inflammations in animals by reducing the level of the strong immune protein TNF-a ( tumor-necrosis factor-a).
Usually CNI-1493 was injected in the bloodstream, but one day Tracey decided to inject it in the brain of a rat, because he wanted to see if the level of the immune proteins would become lower during a stroke. During the experiment Tracey discovered that when the drug was injected in the brain the effect was 100 000 times more powerful than when injected in the bloodstream; so he hypothesized that the drug was acting on neural signals.
He was right. In fact, some minutes after having injected the drug in the brain he observed a burst of activity through the vagus nerve of the rat.
So, the vagus nerve is a pathway of neurons that regulates many involuntary actions of our body, as heart rate, breathing and muscle contractions that push the food to the gut.
As the vagus nerve controls all these actions, Tracey thought that it could regulate inflammations too. This hypothesis was correct; in fact, when he cut the vagus nerve, the effect of the drug disappeared quickly. The meaning of this experiment was crucial: if one could stimulate the vagus nerve, the drug would not be necessary anymore.
Is it now that Tracey made a central experiment.
He injected in the rat a fatal dose of endotoxin, a component of bacterial cells’ wall that sends animals into a spiral of inflammation, organ failure and death.
Then he stimulated the vagus nerve of the rat with an electrode and he found out that the quantity of the TNF-a in the rat was one-quarter lower than its quantity in an untreated rat.
Tracey immediately understood that the vagus-nerve stimulation could be useful in medicine field as a way to block the peaks of TNF-a and other inflammatory molecules.
Till that moment companies were using implantable stimulators only to treat epilepsy, but he wanted to use it also for inflammations; so, to reach this purpose, he needed to present a clear plan of how it might work.
Tracey’s team performed a series of animal experiments to identify where and how vagus-nerve stimulation acted: they tried to cut the nerve in different places and they used drugs that block specific neurotransmitters. These experiments seemed to show that, when the vagus is zapped with electricity, a signal goes into the abdomen and then through a second nerve into the spleen, which can be considered as a bus stop where immune cells park for a while before returning in the bloodstream.
Tracey’s team found out also that the nerve entering the spleen releases a neurotransmitter called noradrenaline, which communicates directly with white blood cells in the spleen called T cells. The junctions between nerve and T cell actually are similar to synapses between two nerve cells and, when stimulated, the T cells release another neurotransmitter, called acetylcholine, which binds to macrophages in the spleen.
These are the immune cells that normally send TNF-α into the bloodstream when an animal receives endotoxin. Exposure to acetylcholine prevents macrophages from producing the inflammatory protein.
What’s more, other scientists found out that all this complex, which uses hybrid neuron-T cells synapses, has been discovered also in other parts of our body, such as gut, lymph nodes and thymus and we have now understood that the hybrid neurons-T cells belong to the sympathetic system and they stimulate the T cells for the production of noradrenaline.
FRIScIence 