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Inflammation is the body’s natural response to infection or physical injury. However, this response may be enhanced in inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. In such cases, inflammatory processes can damage healthy cells and lead to detrimental consequences for the entire body. Because the vagus nerve is known to play a key role in controlling inflammation, the researchers identified a specific receptor there that, when stimulated, could lead to a significant reduction in inflammatory symptoms in mice. Ultimately, this discovery could lead to more targeted treatments for various inflammatory diseases.
Throughout our body, inflammation is mediated and controlled by the vagus nerve. This nerve is made up of over 100,000 individual nerve fibers that travel from the brain to the organs and carry sensory information. During an infection, this nerve doses the inflammatory response, which, among other things, promotes healing. Some studies suggest that in the case of an autoimmune disease, there are areas of exacerbation of inflammation, in particular, due to the lack of control at the level of the vagus nerve.
Thus, previous studies have tested the hypothesis that stimulating this nerve may be a promising way to combat inflammation caused by inflammatory diseases. However, non-specific or inappropriate stimulation of nerve fibers can have unforeseen consequences and reduce the effectiveness of therapy. For example, clinical trials have documented significant side effects (on the vocal cords and cough reflex system) with global vagus nerve stimulation.
Namely, that “the vagus nerve is one of the most important nerves in our body that helps us maintain our daily functions such as breathing and heart rate,” explained Stravos Zanos, assistant professor at the Institute of Medicine. York, who did research on electrical stimulation of the vagus nerve. Therefore, it is very important to stimulate this particular nerve in the hope of developing effective therapeutic strategies against inflammatory diseases.
New research, also from the Feinstein Institute, reveals a novel strategy in this idea to target a specific inflammatory protein receptor located at the level of the vagus nerve. Previous research has shown that vagus nerve stimulation can alleviate the symptoms of inflammation, as a kind of “brake”. But until now, “we didn’t know what was slowing down,” said Kevin J. Tracy, a Feinstein researcher and co-author of the new study.
On the other hand, other studies have also demonstrated the involvement of transient ankyrin receptor-1 (TRPA1) in inflammatory processes. Located at the level of the vagus nerve, this receptor is sensitive to changes in calcium concentration seen in inflammation. This receptor will also allow detection of certain inflammatory proteins such as bradykinin and cytokines. However, the exact role that TRPA1 may play in inflammation remains relatively unknown, especially when these receptors are stimulated by specific cytokines. A new study published in the journal Molecular Medicine aims to decipher the mechanisms associated with the TRPA1 receptor, with the hope of stimulating the vagus nerve more precisely and possibly leading to more effective therapy (against inflammatory diseases).
Receptor that detects and controls inflammation
To pinpoint the role of TRPA1, the researchers genetically engineered mice to lack the receptor. They were then injected intraperitoneally with interleukin 1-beta, an inflammatory cytokine that causes fever. After observations, it was found that in genetically modified mice, the body temperature was maintained at a normal level, while in control mice, hypothermia developed.
Second, the researchers injected 19 mice with a toxic molecule that causes a septic infection. By causing an overproduction of cytokines, this type of infection is potentially fatal. In 10 mice, TRPA1 receptors were stimulated using optogenetics (a technique that allows a gene to be activated or deactivated using light). After injection of the toxic molecule, this group produced half as many cytokines as compared to mice in which TRPA1 receptors were not activated. The damage associated with sepsis has also been significantly reduced.
These results demonstrate the predominant role of the TRPA1 receptor in the detection of inflammation as well as in its control. It will be “new insights into how the brain and nervous system interact with the immune system to control the effects of infection and injury,” concludes Tracey.