What causes itching? It’s a question that many have asked themselves as children. But science, for reasons that go beyond simple infantile curiosity, is also interested in solving what is defined still today a mystery not completely solved. A team of researchers from Harvard Medical School (HMS) has investigated and announces in a study published in ‘Cell’ that they have new clues that point in a single direction. An unprecedented ‘guilty’ ends up under accusation: it is “a common skin bacterium, ‘Staphylococcus aureus’, which can cause itching by acting directly on nerve cells”, they explain.
For the experts it is “an important piece to the long-standing puzzle” on the origins of itching and should explain why common skin diseases such as eczema and atopic dermatitis are often accompanied by a persistent need to scratch. The results reported by the authors are based on research conducted on mice and human cells. The thesis is that the balance of microorganisms that keep our skin healthy is often thrown out of balance, allowing S. aureus to thrive, the researchers explain. Until now, it was believed that the itching that occurs in eczema and atopic dermatitis resulted from a resulting inflammation of the skin. But new findings show that this common and so far ‘unsuspected’ microbe causes itching on its own triggering a molecular chain reaction that culminates in the urge to scratch.
“We have a completely new mechanism identified: the protagonist is the ‘Staph aureus’ bacterium, which is found in almost all patients suffering from chronic atopic dermatitis – says senior author Isaac Chiu, associate professor of immunology at the Blavatnik Institute of Hms – We have shown that itching can be caused by microbe itself.” Experiments have shown that it releases a chemical that activates a protein on nerve fibers that transmit signals from the skin to the brain. Treating the test animals with an FDA-approved anti-clotting drug successfully blocked the activating the protein by interrupting this key step in the ‘itch-scratch’ cycle.
The treatment relieved symptoms and minimized skin damage. The results obtained, the experts explain, can guide the development of oral drugs and topical creams for the treatment of persistent itching, which occurs with various conditions linked to an imbalance of the skin microbiome, such as atopic dermatitis, prurigo nodularis, psoriasis. “Itching can be quite debilitating in patients suffering from chronic skin diseases,” notes study first author Liwen Deng, a postdoctoral researcher in the Chiu Lab.
The researchers exposed the mice’s skin to the bacterium, and the animals developed itching that intensified for several days. They also have become hypersensitive to harmless stimuli that do not normally cause itching. Exposed mice were more likely than those who had not come into contact with the bacterium to develop abnormal itching in response to light touch. This overactive response is common in patients with chronic skin conditions characterized by persistent itching. But it can also occur in people without underlying pathologies: just think of that itchy sensation you might feel when wearing a wool sweater. The authors focused on 10 enzymes known to be released by this microbe upon contact with the skin. One by one they eliminated nine suspects, proving that the enzyme called V8 protease was solely responsible for initiating itching in the mice.
The molecular ‘fuse’ that lights it is in a mechanism that starts right here. Human skin samples from atopic dermatitis patients also had more S. aureus and higher V8 levels than healthy skin samples. Analyzes showed that V8 triggers itching by activating a protein called Par1, which is found on neurons in the skin that originate in the spinal cord and carry various signals – touch, heat, pain, itching – from the skin to the brain. Normally, Par1 remains dormant but, upon contact with certain enzymes, including V8, it is activated. “When we started the study, it wasn’t clear whether the itching was the result of inflammation or not,” Deng highlights. “We showed that these things can be decoupled, that you don’t necessarily need inflammation for the microbe to cause itching, but that itching exacerbates the inflammation on the skin.”
Beyond that, scientists asked: why would a microbe cause itching? Evolutionarily speaking, what’s in it for him? One possibility, they say, is that pathogens exploit itch and other neural reflexes to their advantage. For example, previous research has shown that the tuberculosis bacterium directly activates vagal neurons to cause coughing, which may allow it to spread more easily from one host to another. “It’s speculation, but the itch-scratch cycle could benefit microbes and enable their spread to distant body sites and to uninfected hosts,” concludes Deng. “Why do we itch and scratch? Does it help us or does it help the microbe? This is something we could follow up on in the future.”
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