What’s common between a scratchy sweater, a mosquito bite, and poison ivy? A brush with any of them guarantees an itchy spot on the skin. Scratching that itch is extremely tempting because of how satisfyingly good it feels, but there can be consequences. For skin conditions like dermatitis, where itch is a common symptom, scratching can exacerbate the ailment.1 Even though scratching feeds the craving, spawning a vicious itch-scratch cycle, it does not trigger aversion and remains enjoyable, which begs the question: What is the benefit of scratching an itch?
One potential purpose of this evolutionarily conserved behavior is to remove parasites, mites, or other irritants from the skin’s surface. “There are some things about that concept that are off,” said Isaac Chiu, an immunologist at Harvard Medical School, who studies itch. “For example, a mosquito usually bites you and then you feel itchy. You don't scratch right when the mosquito is biting you.”
Now, in a study published today in Science, researchers at the University of Pittsburgh show that scratching is a double-edged sword—it activates the immune system to drive skin inflammation and enhances the host’s defense against bacterial infections.2 These findings can pave the way towards better treatments for skin conditions like eczema by either reducing the resulting inflammation or curbing the need to scratch.
About 10 years ago, Daniel Kaplan, a dermatologist at the University of Pittsburgh, observed that host defenses against microbial skin infections required the involvement of the nervous system. “We found that pain sensing neurons were necessary and sufficient to drive inflammation in the skin. So, we started to think, ‘What about itch? How does itch work in all of this?’” he reminisced.

Daniel Kaplan is a dermatologist at the University of Pittsburgh who studies how itch-sensing neurons modulate immune responses.
Nate Langer, University of Pittsburgh
To answer that question, Kaplan and his colleagues engineered mice lacking a specific type of itch-sensing neuron, preventing them from scratching. When they exposed their ears to different allergens, the ears of the control mice, which scratched their itch, grew thick from inflammation within a day. In contrast, the ears of the mutant mice looked almost normal. “This is not what we were expecting. It was a total surprise,” Kaplan said. In fact, Kaplan observed the same result with control mice that were wearing tiny Elizabethan collars to prevent scratching, suggesting that the effects are the result of scratching rather than itching. This motivated him to explore the mechanism by which scratching modulates inflammation.
One of the major immune cells driving inflammatory reactions is the mast cell.3 Upon encountering antibodies targeting an allergen, mast cells become activated and release a flurry of molecules, including histamine. After examining the ear tissue more closely, the team observed a fluid buildup, neutrophil infiltration, and increased expression of the tumor necrosis factor gene in the control mice—all indicators of mast cell activation. In contrast, the unscratched ears of the mutant mice showed significantly less swelling and fewer activated mast cells.
To understand how scratching stimulated mast cells, Kaplan and his colleagues explored two possible mechanisms: activation through allergens or through factors released by surrounding cells. Pain-sensing neurons can turn on mast cells by releasing neuropeptides that bind to receptors on immune cells. When the team chemically stimulated these receptors in mice ears, they observed that inflammation levels were similar in both scratching and non-scratching mice, indicating that scratching could activate pain-sensing neurons. However, when they activated mast cells by stimulating the receptors that respond to allergens, the researchers noticed a different pattern. After an initial spike in inflammation, the ears of mice that couldn’t scratch eventually showed reduced swelling, but those of control mice remained inflamed. Based on these findings, Kaplan hypothesized that scratching could exacerbate inflammation by amplifying allergen-mediated mast cell activation with the pain-sensing pathway.
Researchers have previously shown that itch and pain are deeply connected, but the interactions between the two are only partially understood.4 “When you scratch, you scratch until you damage the skin, but also scratch until you feel pain,” said Chiu, who was not involved in the study. Kaplan speculated that scratching could stimulate the release of peptides from pain-sensing neurons, many of which are known to bind to mast cell receptors. After measuring the levels of a few such molecules, the researchers observed that the neuropeptide substance P varied depending on whether scratching occurred. To further investigate its role, they engineered mice lacking the genes for substance P and its receptor on mast cells. When exposed to an allergen, these mice exhibited reduced ear inflammation compared to normal mice. Similarly, inhibiting pain-sensing neurons produced the same anti-inflammatory effect. Notably, all groups scratched at similar levels, indicating that scratching stimulates pain-sensing neurons to release substance P, which in turn activates mast cells and increases inflammation.
Inflammation is the body’s response to harmful stimuli. Skin conditions like dermatitis that induce itching are associated with an altered skin microbiome and superficial Staphylococcus aureus infections.5 So, Kaplan wondered if scratching-induced inflammation could work to protect the host against pathogens. To test this, the team infected the mice with S. aureus, waited a few days for adaptive immunity to develop, and then induced allergen-mediated mast cell activation in their ears. The mice that were allowed to scratch their ears showed the expected increase in inflammation but also had lower levels of S. aureus compared to those that did not scratch. This suggests that scratching can protect the host by reducing bacteria on the skin, which is a brand-new function for scratching.
This new understanding of the interplay between itch, the immune system, and the nervous system could lead to the development of more effective therapies for managing itch and reducing inflammation in skin disorders. “This is really fertile territory to develop therapies that can modulate immune responses in the skin without having to immunosuppress the whole body,” Kaplan said. His team has developed a topical cream based on a natural compound that targets the pathways described in the paper.
In this study, the researchers focused exclusively on short-term scratching. But what about conditions like psoriasis and scabies, where the itch just won’t budge? The team has already started exploring the point at which the benefits of scratching no longer outweigh its negative effects. “Some scratching might provide a benefit against Staph aureus, but if you scratch a lot, you're going to cause a lot of damage to the skin,” Kaplan explained. “So, if you have an itch, don’t scratch it. It’ll only make the rash worse.”
- Cevikbas F, Lerner EA. Physiology and pathophysiology of itch.Physiol Reviews. 2020;100(3):945-982.
- Liu AW, et al. Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation.Science. 2025;387:eadn9390.
- Galli SJ, Tsai M. IgE and mast cells in allergic disease.Nat Med. 2012;18(5):693-704.
- Sun S, et al. Leaky gate model: Intensity-dependent coding of pain and itch in the spinal cord.Neuron. 2017;93(4):840-853.e5.
- Kobayashi T, et al. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis.Immunity. 2015;42(4):756-766.