What can trigger an itch? Scientists have found a new culprit

If you've got itchy skin, it could be that a microbe making its home on your body has produced a little chemical that's directly acting on your skin's nerve cells and triggering the urge to scratch.

That's the implication of some new research that shows how a certain bacteria, Staphylococcus aureus, can release an enzyme that generates an itchy feeling.

What's more, a drug that interferes with this effect can stop the itch in laboratory mice, according to a new report in the journal Cell.

"That's exciting because it's a drug that's already approved for another condition, but maybe it could be useful for treating itchy skin diseases like eczema," says Isaac Chiu, a scientist at Harvard Medical School who studies interactions between microbes and nerve cells.

He notes that eczema or atopic dermatitis is actually pretty common, affecting about 20% of children and 10% of adults.

In the past, says Chiu, research on itchy skin conditions has focused on the role of the immune response and inflammation in generating the itch sensation. People with eczema often take medications aimed at immune system molecules.

But scientists have also long known that people with eczema frequently have skin that's colonized by Staphylococcus aureus, says Chiu, even though it's never been clear what role the bacteria might play in this condition.

Chiu's previous lab work had made him realize that bacteria can directly act on nerve cells to cause pain.

"So this made us ask: Could certain microbes like Staphylococcus aureus also particularly be in some way linked to itch?" says Chiu. "Is there a role for microbes in talking to itch neurons?"

He and his colleagues first found that putting this bacteria on the skin of mice resulted in vigorous scratching by these animals, leading to damaged skin that spread beyond the original exposure site.

The researchers then identified a bunch of enzymes released by this bacteria once it started growing on skin. They tested each one, to see if it triggered itching.

It turns out that one bacterial enzyme, called protease V8, seemed to do the job.

Additional work showed how this bacterial enzyme activates a protein that's found on nerve cells in the skin. That generates a nerve signal that the brain experiences as an itch.

"Our study is really the first to show that the microbe can directly activate itch neurons and cause itch," says Liwen Deng, a researcher at Harvard Medical School.

The protein activated by the bacteria is also present on certain blood cells and is involved in blood-clotting. And as it turns out, that protein activation on skin neurons can be blocked by an anti-clotting medication that's already on the market.

"We just got lucky that that was already an FDA-approved compound," says Deng, who says that they just tried it out in their lab animals. "We treated them orally with the drug and it completely blocked the itching and scratching that we normally observe when we apply bacteria to mice."

It might be possible to make the same drug in some kind of skin cream or topical medication, she says.

These new findings are "amazing," says Brian Kim, a dermatologist and researcher at the Ichan School of Medicine at Mount Sinai in New York has studied the immune factors that cause itching.

He notes that in the past, some dermatologists treated eczema with diluted bleach baths or oral antibiotics, on the theory that killing off Staphylococcus aureus might have some beneficial effect.

"We were so desperate for anything," says Kim, who points out that itchy conditions can be acutely uncomfortable and even debilitating, as constant scratching can result in damaged skin, poor sleep, and feelings of embarrassment.

This new research opens up a whole new way of thinking about what might produce the urge to scratch, he says.

"Maybe there are other bacteria that live on your skin and can also cause itching," says Kim. "They could be driving itching by directly interacting with your nerves."

A future treatment that aimed at specific itch-producing molecules would allow a much more targeted approach that wouldn't damage beneficial bacteria on and in the body, says Kim.

It's possible that certain bacteria have evolved to provoke people to scratch, the researchers speculate, because scratching helps these microbes to spread to other people or other parts of the body. Or, scratching might damage the skin in a way that lets bacteria get a better foothold.

"We're not actually sure why Staphylococcus aureus would want to be inducing an itching response and whether it's beneficial for the microbe," says Deng. "We're really interested in testing that."

She says even though itching is commonplace, "it's still kind of an enigma to scientists how exactly the mechanisms behind it work."

"We think that we've kind of identified a new way to think about what causes itch," says Deng, "and how we can potentially treat it."