Belgian Science Reveals Why People Itch 0 16

When you itch, the brain receives a signal about when to stop. This feeling of "enough scratching" does not occur by chance. Scientists have identified key molecular and neural mechanisms that provide this built-in braking system, offering new insights into how the body controls itching and why this control is disrupted in chronic conditions.

In a new study conducted at the University of Leuven laboratory in Brussels, researchers uncovered an unexpected role of the ion channel TRPV4 in mechanical itching. TRPV4 belongs to a family of ion channels that function as molecular "gates" in the membranes of sensory neurons, allowing ions to move in response to physical or chemical stimuli. These channels help the nervous system perceive temperature, pressure, and tissue stretch. Although it has long been assumed that TRPV4 is involved in mechanical sensation, its role in itching, especially chronic itching, has remained contentious.

To clarify this issue, the team created a genetic model of mice in which TRPV4 was removed only from sensory neurons. This approach avoided the limitations of previous studies where the channel was removed from all tissues, making it difficult to determine its specific site of action. Using a combination of genetic methods, calcium imaging, and behavioral tests, the researchers demonstrated that TRPV4 is present in neurons traditionally associated with touch – low-threshold mechanoreceptors Aβ (Aβ-LTMR), as well as in subgroups of sensory neurons involved in transmitting signals of itch and pain, including cells expressing TRPV1. When the researchers induced chronic itching in mice, similar to atopic dermatitis, the results were striking. Mice lacking TRPV4 in sensory neurons scratched less frequently, but each scratching session lasted significantly longer than usual.

The data show that TRPV4 does not simply cause itching. In mechanosensory neurons, this channel is involved in triggering a negative feedback signal – a neural signal that informs the spinal cord and brain that scratching has been sufficient. Without this signal, the feeling of relief diminishes, and scratching becomes excessive. In other words, TRPV4 is part of an internal neural circuit that helps stop the scratching process. The study's findings also indicate that the role of TRPV4 in the formation of itching is much more complex than previously thought. While in skin cells the channel promotes the sensation of itching, in neurons it helps control and limit these sensations. This dual function is significant for the development of new anti-itch medications.