Itch is a dominant symptom in dermatitis (eczema), and scratching promotes cutaneous inflammation, thereby worsening disease. However, the mechanisms through which scratching exacerbates inflammation and whether scratching provides benefit to the host are largely unknown. New research conducted in mice uncovers the dual nature of scratching: although it can worsen skin inflammation, it can also boost immune defenses against bacterial infections at the injury site.
Scratching synergizes with FcεRI mast cell activation to drive allergic skin inflammation. Image credit: Liu et al., doi: 10.1126/science.adn9390.
Scratching is an often irresistible, stereotypical, and evolutionarily conserved behavioral response to the sensation of cutaneous itch.
In many common skin diseases, such as dermatitis, protracted itching is the dominant symptom and represents a substantial source of morbidity.
Scratching in response to itch is clinically well recognized to exacerbate dermatitis and is pathogenic in some diseases.
However, scratching an itch is often a pleasurable sensation and does not trigger avoidance behavior, which suggests that it may provide some benefit to the host.
“Scratching is often pleasurable, which suggests that, in order to have evolved, this behavior must provide some kind of benefit,” said University of Pittsburgh’s Professor Daniel Kaplan.
“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, Professor Kaplan and colleagues 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.
The findings suggest that scratching serves both as a pathological driver of inflammation and an evolutionary mechanism to bolster protection against infection.
“The finding that scratching improves defense against Staphylococcus aureus suggests that it could be beneficial in some contexts,” Professor Kaplan said.
“But the damage that scratching does to the skin probably outweighs this benefit when itching is chronic.”
The findings appear in the journal Science.
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Andrew W. Liu et al. 2025. Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation. Science 387 (6733); doi: 10.1126/science.adn9390
Source : Breaking Science News