Scratching and allergic skin inflammation

Scratching an itch can feel good. It can also activate immune defenses, according to new research. Hananeko_Studio / Shutterstock

Many skin diseases, such as dermatitis, feature a prolonged itching sensation. This sensation encourages scratching, which can bring temporary relief but may also promote skin inflammation and more itching. This prompts further scratching, leading to a vicious cycle of worsening disease. Yet scratching is an automatic response to itch in many species. This suggests that it evolved because it provides some benefit. How scratching promotes inflammation, or what the benefit of scratching might be, are not well understood.

A team of researchers, led by Dr. Daniel Kaplan at the University of Pittsburgh, sought to answer these questions. To investigate, they used genetically engineered mice and models of allergic skin reactions. Their results appeared in Science on January 31, 2025.

The research team began by applying compounds that elicit allergic skin reactions to the ears of mice. Doing so caused the ear tissue to swell and fill with inflammatory immune cells called neutrophils. But in mice that lacked itch-sensing neurons, this inflammation was reduced. These mice scratched their ears less than control mice as well. Collars that physically prevented the mice from scratching also reduced this inflammation.

Itching and neutrophil infiltration are both triggered by the activity of immune cells called mast cells. Mice that scratched less, the researchers found, had reduced mast cell activation. Next, the researchers tried activating mast cells directly, via the mechanism by which allergens do. Mice that scratched less still had less inflammation. This suggested that scratching and allergens activate mast cells via separate, synergistic mechanisms.

Besides allergens, a compound called substance P can also activate mast cells. Substance P is produced by other, pain-sensing, neurons. The team found that mice lacking the gene for either substance P or its receptor on mast cells had less inflammation than control mice. Yet the engineered mice didn’t scratch any less than the control mice. The team saw similar results when the pain-sensing neurons in mice that produce substance P were inactivated.

Another function of mast cells is to help defend the body against skin infection. So, the researchers infected the skin of mice with Staphylococcus aureus bacteria. Once again, mice that scratched less had less inflammation and mast cell activation than control mice. But they also had more S. aureus in their skin 24 hours after infection than the controls.

These results suggest that mast cell activation by an allergen causes some initial inflammation and itching. Scratching then causes pain-sensing neurons to release substance P. Substance P further activates mast cells, leading to more inflammation. This increased inflammation can enhance the body’s defenses against skin infections.

“At first, these findings seemed to introduce a paradox: If scratching an itch is bad for us, why does it feel so good?” Kaplan says. “Scratching is often pleasurable, which suggests that, in order to have evolved, this behavior must provide some kind of benefit. Our study helps resolve this paradox by providing evidence that scratching also provides defense against bacterial skin infections.”

Targeting mast cells or the neurons that promote their activation could prove to be a promising approach for treating itchy inflammatory diseases like dermatitis and eczema.

—by Brian Doctrow, Ph.D.