If you experience itching, scratching it will usually subside after a while. Scientists have discovered a part of the biological system that tells the brain when enough scratches have occurred. The findings reveal how the nervous system naturally limits scratching and may help explain why this process doesn’t work in people with chronic itch disorders. The findings were presented at the 70th Annual Meeting of the Biophysical Society.
Researchers from Roberta Guardani’s lab at the University of Leuven in Brussels have identified an unexpected role for a molecule known as TRPV4 in itch induced by mechanical stimuli such as scratching.
“We initially studied TRPV4 in the context of pain,” Guardani explained. “But what emerged very clearly was not the pain phenotype, but the disruption of itch, and in particular how scratching behavior is controlled.”
TRPV4 and the nervous system
TRPV4 is part of a family of ion channels that act like small molecular gateways for sensory neurons. These channels allow ions to pass through the cell membrane in response to physical or chemical changes. These help the nervous system detect sensations such as temperature, pressure, and tissue stress.
Scientists have long suspected that TRPV4 plays a role in sensing mechanical stimuli, but its involvement in itch, especially chronic itch, remains unclear and hotly debated.
To investigate more precisely, Guardani’s team created genetically engineered mice that removed TRPV4 only from sensory neurons. Previous studies had deleted molecules throughout the body, making it difficult to determine exactly where it was working.
Using genetic analysis, calcium imaging, and behavioral tests, researchers discovered that TRPV4 appears in touch-sensitive neurons known as Aβ low-threshold mechanoreceptors (Aβ-LTMRs). This channel was also present in certain sensory neurons associated with itch and pain pathways, such as those expressing TRPV1.
Why I can’t stop scratching sometimes
Next, the research team created a chronic itching condition similar to atopic dermatitis in mice. The results surprised the researchers. Mice lacking TRPV4 in their sensory neurons scratched less frequently overall, but each scratching episode lasted much longer than normal.
“At first glance, it seems paradoxical,” Guardani said. “But it actually revealed something very important about how itch is controlled.”
Research shows that TRPV4 does more than just cause the sensation of itching. Instead, it appears to help activate negative feedback signals in mechanosensory neurons. This signal tells the spinal cord and brain that scratching has provided sufficient relief.
Without this feedback system, scratching becomes less satisfying and you end up scratching for longer periods of time. Therefore, the researchers say, TRPV4 may function as part of an “anti-scratch” mechanism inside the nervous system.
“When we scratch an itch, at some point we stop because there is a negative feedback signal that we are satisfied,” Guardani explained. “Without TRPV4, mice don’t feel this feedback, so they keep scratching for much longer than normal.”
Impact on chronic itch treatment
The findings also suggest that TRPV4 plays a more complex role in itch than previously thought. In skin cells, this channel may help cause itching. However, neurons appear to help control and limit scratching behavior.
This difference could be important for future drug development.
“This means that broadly blocking TRPV4 may not be the solution,” Guardani noted. “Future treatments could be more targeted, perhaps acting only on the skin without interfering with the neural mechanisms that tell us when to stop scratching.”
Chronic itch affects millions of people living with conditions such as eczema, psoriasis and kidney disease, but treatment options remain limited. Researchers believe that understanding how the body controls itch, including the signals that tell you when to stop scratching, could ultimately lead to more effective treatments.
