Everyone has happened to have it itching for one reason or another. You scratch and, after a few seconds, a feeling of relief arrives that makes you understand that this can be enough. For years, scholars have focused above all on how itching arises; it was more difficult to understand what made that feeling go away. New research published by researchers at the University of Louvain on Biophysical Journal suggests that a protein present in neurons may also play the role of natural “brake”.. The experiments, conducted on genetically modified micehave shown, in fact, an unexpected result: animals lacking a particular channel (called TRPV4) in the sensory neuronsthey scratched less often, but each episode lasted longer. The data fits into a broader picture built by previous studies, which had already linked this protein to substances such as histamine And serotonin and to the continuous dialogue between skin, neurons And immune cells.
The TRPV4 protein: the ion channel at the center of the study on itch
The protagonist of this story is called TRPV4. Behind this unfriendly name lies a ion channelthat is, a microscopic structure present on the surface of cells that functions like a door. When it receives certain stimuli, this door opens and lets through electrically charged particles, called ionsallowing cells to communicate with each other. These systems participate in the perception of temperature, pressure, pain and, according to numerous research, also of itching. In recent years several studies had already suggested that TRPV4 had a role in itchingalthough it wasn’t clear which one.
In some experiments published on International Journal of Molecular Sciencesmice lacking TRPV4 showed a reduction in scratching caused by substances such as histamine, serotonin And composed 48/80molecules known to induce itching. More research on Acta Dermato-Venereologica indicated that TRPV4 in the skin it could have a different function from that in the neurons. In some skin cells, i keratinocytes (the main cells of the outer layer of the skin) channel appeared to help initiate the itch signal. In neurons, however, it could also have a regulatory function.
The discovery of the mechanism that makes us stop scratching
The story of this new research published on Biophysical Journal it started from another question. Roberta Gualdani and his group atUniversity of Louvain they were studying TRPV4 in relation to pain. The results, however, began to reveal something that didn’t quite fit with the initial idea. The most obvious change was not so much the response to pain, but the animal behavior when the itching appeared.
To understand where the mechanism was hiding, the researchers chose one approach more precise compared to many previous works. They created genetically modified mice so that TRPV4 it would just disappear come on sensory neuronsthe nerve cells responsible for collecting signals from the body and sending them to the central nervous system. In previous studies, however, the protein was eliminated in all tissues at the same time. In such a situation, understanding who is really doing what becomes much more complicated. To understand where he intervened TRPV4 they used tools that allow them to follow what happens in cells while they are active, monitoring changes in the soccera sort of indicator of cellular activity. So they discovered that TRPV4 was present not only in neurons associated with the touchbut also in circuits involved in pain and in itching.
The possible nervous circuit of the stop signal
The most surprising result came when a condition similar to a chronic form of was induced in animals dermatitis. At first glance the observed behavior seemed almost contradictory. Mice devoid of TRPV4 in sensory neurons, in fact, they scratched less oftenbut each episode lasted longer than normal.
This detail has changed the way of interpreting the role of the protein. If TRPV4 were needed only to generate itchingone would simply expect one decrease in scratching. The data, however, suggests something different: it could participate in a system of negative feedback. The term sounds technical, but the concept is familiar: it’s the same principle as thermostat which turns off the heating when the desired temperature is reached. In the case of itching, the nervous system may send a message that communicates: “you’ve scratched enough”. When TRPV4 is missing, this signal appears to weaken. The feeling of relief becomes less effective and the scratching continues longer.
TRPV4 may have different functions in various tissues
The same protein (TPRV4) therefore seems to behave differently based on where it is found. In some cells it could contribute to the appearance of itchingwhile in others it seems to participate in the mechanisms that help keep it under control. Precisely for this reason the researchers urge caution: eliminate or block the TRPV4 indiscriminately it would risk eliminating not only part of the problem, but also part of the system that seeks to limit it.
A fundamental distinction in the development of any future treatments. In fact, it should be remembered that if on the one hand itching, when it is acutehelps us ward off potential threats, when it becomes chronicpersisting for more than six weeks is often linked to skin diseases, neurological problems or other body conditions and can significantly worsen the quality of life of those who suffer from it. The idea is that any future treatments need to be much more targeted and act only on certain ones fabrics or cell types, using as a target, for example, the TRPV4s that trigger itching, without blocking those that turn it off.
