February 19, 2025 from Medscape
Scratching is often seen as a sign of irritation — a symptom to suppress in inflammatory conditions like dermatitis. But emerging research suggests it may serve a deeper biological purpose. A recent study in Science shows that scratching helps regulate the immune system and the skin’s microbiome, potentially evolving as a natural defense against infection.
Scratching Sparks an Immune Cascade
Researchers studied mice genetically modified to lack MrgprA3-expressing neurons — the cells responsible for triggering itch. These mice, as well as regular mice physically prevented from scratching, failed to mount an immune response after exposure to allergens. In contrast, mice allowed to scratch showed neutrophil infiltration and mast cell activation — key signs of localized inflammation.
The findings suggest that it’s not the itch sensation itself, but the act of scratching, that activates the immune system.
Delving deeper, researchers found that scratching stimulates TRPV1-expressing neurons, which release a neuropeptide called substance P. This, in turn, prompts mast cells to release tumor necrosis factor, ramping up immune activity in the skin. Blocking this pathway — either by silencing TRPV1 neurons or inhibiting substance P — prevented the immune response, while triggering the neurons with capsaicin recreated it.
A Defense Against Bacteria
So why is this mechanism tied to scratching rather than direct immune activation? The answer may lie in the skin’s microbiome.
The same study found that scratching changes the bacterial landscape at the site of inflammation. In particular, scratching reduced levels of potentially harmful bacteria like Staphylococcus aureus. This suggests scratching does double duty — not only triggering an immune response but also helping clear dangerous microbes from the skin’s surface.
Balancing the Good and Bad
These findings help explain why scratching is an instinctive and even pleasurable behavior across species — from fish to humans. It may be a built-in survival mechanism, offering protection against infection in the absence of modern medicine.
But there’s a tradeoff. While scratching can activate useful immune defenses, it can also aggravate skin conditions like eczema by driving excessive inflammation.
Understanding the neuroimmune pathway behind scratching opens the door to new treatments. Future therapies might reduce harmful inflammation while preserving the antimicrobial benefits of this ancient behavior — helping patients manage chronic itch without triggering flare-ups.
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