Scratching an itch can worsen skin inflammation, but it can also boost immune defenses against bacterial infections at the injury site, new research suggests.
The findings, which appear in Science, shed light on a pharmacologically targetable pathway that explains how scratching triggers inflammation, resolving the paradox of scratching as both a harmful pathological process and a beneficial evolutionary adaptation.
Scratching can aggravate the condition by promoting inflammation in a self-perpetuating “itch-scratch cycle,” where the scratching intensifies the itch and can exacerbate the injury. Yet unlike pain, which typically causes an aversion response, scratching can feel pleasurable, which suggests it might serve some adaptive benefit. However, the mechanisms by which scratching contributes to skin inflammation and whether the itch-scratch reflex offers any benefits to the host remain poorly understood.
“At first, these findings seemed to introduce a paradox: If scratching an itch is bad for us, why does it feel so good?” says senior author Daniel Kaplan, MD, PhD, professor of Dermatology and Immunology at the University of Pittsburgh in Pittsburgh, PA, in a news release. “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.”
Using a novel genetically modified mouse model, researchers .explored how eliminating the function of itch-sensing neurons called nonpeptidergic 2 (NP2) affects the connection between itch, scratch and inflammation. They discovered that scratching activates pain-sensing neurons that release substance P (SP), which stimulates mast cells to increase inflammation, mainly by attracting neutrophils. However, while scratching can aggravate issues like dermatitis, it may also help host immune defense by reducing bacteria, such as Staphylococcus aureus, during infections. Moreover, scratching can influence the skin’s microbiome at the injury site, potentially preventing microbiota imbalances, although chronic conditions like atopic dermatitis complicate this. According to the authors, the findings suggest that scratching serves both as a pathological driver of inflammation and an evolutionary mechanism to bolster protection against infection.
“In contact dermatitis, mast cells are directly activated by allergens, which drives minor inflammation and itchiness,” explains Kaplan. “In response to scratching, the release of substance P activates mast cells through a second pathway, so the reason that scratching triggers more inflammation in the skin is because mast cells have been synergistically activated through two pathways.”
In experiments led by coauthor Marlies Meisel, PhD, assistant professor of immunology at Pitt, the team showed that scratching reduced the amount of Staphylococcus aureus, the most common bacteria involved in skin infections, on the skin.
“The finding that scratching improves defense against Staphylococcus aureus suggests that it could be beneficial in some contexts,” says Kaplan. “But the damage that scratching does to the skin probably outweighs this benefit when itching is chronic.”
Now, the researchers are investigating new therapies for dermatitis and other inflammatory skin conditions such as rosacea and urticaria that suppress inflammation by targeting receptors on mast cells.
