Scratching itchy skin can worsen inflammation and boost immune response.

The study's findings illuminate the pharmacologically targeted pathway explaining how scratching induces inflammation, resolving the paradox of scratching being both a harmful pathological process and a beneficial evolutionary adaptation.

Scratching is a natural, instinctive response to the sensation of itch, playing a crucial role in various skin conditions and injuries, such as dermatitis and insect bites, where chronic itching can be a primary source of discomfort. Scratching can exacerbate the issue by promoting inflammation in a self-perpetuating cycle of "itch-scratch," where scratching intensifies the itch and may worsen the damage.

However, unlike pain, which typically triggers a rejection response, scratching can be pleasurable, suggesting it may provide some adaptive benefit. Yet, the mechanisms by which scratching contributes to skin inflammation and whether the scratching reflex offers any benefit to the host remain poorly understood. Utilizing a new genetically modified mouse model, Andrew Liu and his colleagues investigated how the removal of the function of itch-sensing neurons, known as non-peptidergic 2 (NP2), affects the relationship between itch, scratching, and inflammation.

Liu and colleagues found that scratching activates pain neurons that release substance P (SP), which stimulates mast cells to enhance inflammation, primarily by attracting neutrophils. However, while scratching may worsen issues like dermatitis, it can also assist the host's immune defense by reducing bacteria such as Staphylococcus aureus during infections. Furthermore, scratching may influence the skin microbiome at the site of damage, potentially preventing microbiota imbalance, although chronic conditions like atopic dermatitis complicate this task.

According to the authors, the data suggests that scratching serves as both a pathological factor in inflammation and an evolutionary mechanism for protection against infections. "In addition to identifying a previously unrecognized neuroimmune circuit of 'itch-scratch,' Liu and colleagues' findings may lay the groundwork for discoveries that could help individuals suffering from chronic itch," the researchers write in the journal Perspective.