PITTSBURGH — If you were to accidentally dip your thumb into boiling water, the searing pain would instantly trigger a response in your brain, urging you to pull away immediately. Not only would this reflex protect you in the moment, but it would also create a lasting memory — one that warns, "Don't do that again!"

So why doesn't our brain respond the same way when we get a mosquito bite or have a brush with poison ivy? We know scratching only makes these things worse — our parents told us so, and experience has proven them right. Yet despite the risk of spreading a rash or worsening the irritation, the urge to scratch is irresistible. It just feels so darn good to give in.

Researchers at the University of Pittsburgh may have uncovered a new way to treat rosacea and other inflammatory skin conditions by targeting mast cells, a key player in immune responses.

Their findings, published last month in the journal Science, found that SYM2081, a compound that activates a specific receptor on mast cells, successfully reduced inflammation in animal models and human skin samples. The takeaways could lead to new topical treatments for conditions such as urticaria, or chronic hives, and rosacea, offering relief for millions who suffer from chronic skin irritation and allergic reactions.

"Scratching an itch can be so, so pleasurable. So in that regard, it's reinforced behavior, suggesting that there should be a benefit to it from an evolutionary standpoint," said Daniel Kaplan, professor of dermatology and immunology at Pitt and a senior author on the study. "We found that when you scratch, you end up activating these pain-sensing neurons that trigger inflammation ... but at the same time, we also found that scratching, at least in a very short-term, acute setting, actually helps control bacteria on the skin. And so in that way, it provides a benefit."

When we scratch our skin after an insect bite, this activates the mast cells, immune cells responsible for many allergic reactions, which then "release a whole bunch of small molecules that trigger inflammation locally" and could lead to hives or the spread of the rash area, Kaplan said.

While studying the inflammatory response caused by mast cells, it became evident to the team that mast cells were playing an "unappreciated role in a lot of these diseases, certainly in hives," Kaplan said. By manipulating these mast cells, the team hopes to pave the way for new topical treatments to prevent itching, hives and other symptoms of skin conditions driven by them.

What are mast cells?

Mast cells are a part of the immune system that are made in our bone marrow and then move through the bloodstream into tissues, according to The Cleveland Clinic. Mature mast cells live in tissues throughout the body and protect our bodies from hazards by fighting infections and regulating our organs.

These cells can become overprotective and react to harmless things in the environment, causing conditions such as seasonal allergies or allergic asthma. Mast cell activation can sometimes cause anaphylaxis, a serious allergic reaction that can be characterized by a number of symptoms including hives, narrowing of airways, swollen tongue, low blood pressure, fainting and more.

Mast cells drive conditions like chronic hives — also called urticaria — and rosacea, which is characterized by flushing and redness, especially on the face. Both conditions are particularly challenging to treat, Kaplan said. Additionally, mast cells may also play a role in diseases like eczema, but he said more study is required to verify that connection.

Mast cells also play key roles in anti-tumor immunity and tumor regulation for cancer patients. They influence tumor cells and their surrounding environment and can either promote or suppress cancer growth, according to a National Institutes of Health study.

"What these findings highlight is that targeting these cells may be a very helpful therapeutic approach to treat these skin diseases," Kaplan said.

The team also examined how scratching the itchy, swollen rashes associated with allergic contact dermatitis triggers further inflammation that worsens symptoms and slows healing.

To determine what drives this vicious cycle, the team used itch-inducing allergens to induce eczema-like symptoms on the ears of normal mice and those that don't get itchy because they lack an itch-sensing neuron.

When the normal mice scratched their ears, the tissues became swollen and filled with inflammatory immune cells called neutrophils. But the inflammation and swelling were much milder among mice that lacked the ability to sense itchiness and normal mice that were dissuaded from scratching by tiny Elizabethan collars, similar to a "cone of shame" that some pets sport after visiting the vet. This experiment confirmed that scratching further aggravates the skin.

However, during their trials the team discovered that there is one solidly beneficial side effect to scratching. In experiments led by study coauthor Marlies Meisel, assistant professor of immunology at Pitt, the team showed that scratching reduced the amount of Staphylococcus aureus, the most common bacteria involved in skin infections, on the skin.

"The finding that scratching improves defense against Staphylococcus aureus suggests that it could be beneficial in some contexts," said Kaplan.

Those same mast cells that often increase inflammation can also "release a lot of molecules that will call the immune system to that site and help prevent infection. And they can also release small molecules that can actually directly combat infection," he said.

Overall, however, it's still best to listen to mom and resist the urge to scratch, he quickly added. "The damage that scratching does to the skin probably outweighs this benefit when itching is chronic."

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