Mice lacking the TRPV4 protein scratch less frequently but can’t stop once they start
People who can’t stop scratching their itch might finally have someone to blame.
In mice (and probably in humans), a protein called TRPV4 is involved in both trigger an itch and stop it after scratching, explains neuroscientist Roberta Gualdani. She will present her results on February 24 at the annual meeting of the Biophysical Society in San Francisco.
Among other places in the body, this protein is found in the nerves involved in pain and itching. Gualdani, of the Catholic University of Louvain in Brussels, and his colleagues therefore thought that TRPV4 could be a pain sensor. Its role in itching was controversial. It turns out that the protein is also located in nerve cells that detect touch and other mechanical sensations, including scratchingthe researchers discovered.
Gualdani’s team genetically engineered mice to lack TRPV4 in certain nerve cells. These mice responded to pain like mice with intact proteins.
Next, the team applied a vitamin D-like substance to the mice to mimic eczema, a chronic inflammatory skin disease that affects about 10 percent of people in the United States and causes itchy, dry skin and rashes. Mice that made TRPV4 had many brief periods of scratching. Mice lacking proteins in their nerves don’t scratch as often, suggesting that TRPV4 is involved in triggering the itch. It’s not the only one molecule involved so the mice were still itchy sometimes.
When mice lacking protein scratch, they “experience a very, very long episode of scratching before [they] stop. So this suggests that they lost the regulatory mechanism that caused the scratch relief,” says Gualdani.
The findings could be important for understanding chronic itch in humans. Ultimately, this knowledge could lead to treatments for eczema and other itchy skin conditions. But it’s a delicate balance, Gualdani says. Substances that deactivate TRPV4 can make itching less frequent, but reducing the protein’s activity too much could mean people have trouble stopping scratching once they start. Conversely, increasing the activity of the protein may relieve stubborn itch, but could lead to even more frequent itching and scratching.