Scratching found to both aggravate inflammation and boost immune defenses

New research uncovers the dual nature of scratching an itch; although it can worsen skin inflammation, it can also boost immune defenses against bacterial infections at the injury site. The findings 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 is a natural, instinctive response to the sensation of itching, and it plays a central role in many skin conditions and injuries, such as dermatitis and insect bites, where chronic itching can be a major source of discomfort. 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. Using a novel genetically modified mouse model, Andrew Liu and colleagues explored how eliminating the function of itch-sensing neurons called nonpeptidergic 2 (NP2) affects the connection between itch, scratch and inflammation.

Liu et al. 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. "Beyond defining a previously unidentified neuroimmune itch-scratch circuit, the findings of Liu et al. may lay a foundation for discoveries to help people suffering from chronic itch," writes Aaron Ver Heul in a related Perspective.