by A breakthrough study conducted by scientists at Harvard Medical School has revealed that a commonly found skin bacterium, Staphylococcus aureus, can directly cause itch by acting on nerve cells. The findings, published in Cell, shed new light on the long-standing puzzle of itch and provide an explanation as to why skin conditions like eczema and atopic dermatitis are often accompanied by persistent itch.
Traditionally, itch associated with these conditions was believed to be a result of skin inflammation. However, the study shows that S. aureus is solely responsible for inducing itch by initiating a molecular chain reaction that leads to the urge to scratch.
The skin microbiome, a delicate balance of microorganisms that keep our skin healthy, is often disrupted in these conditions, allowing S. aureus to thrive. The researchers discovered that S. aureus releases a chemical that activates a protein on nerve fibers responsible for transmitting signals from the skin to the brain. By treating animals with an FDA-approved anti-clotting medicine, the activation of the protein was blocked, interrupting the itch-scratch cycle and providing relief from symptoms.
These findings have significant implications for the development of oral medicines and topical creams to treat persistent itch in conditions associated with an imbalance in the skin microbiome, such as atopic dermatitis, prurigo nodularis, and psoriasis. The excessive scratching that typically occurs with these conditions can cause further skin damage and worsen inflammation.
The study involved exposing the skin of mice to S. aureus, which resulted in intensifying itch and worsening skin damage. The mice also exhibited hypersensitivity to innocuous stimuli that would not typically cause itch. This hyperactive response, known as alloknesis, is often observed in patients with chronic skin conditions characterized by persistent itch.
Through a series of experiments, the researchers identified a bacterial enzyme called protease V8 as the key initiator of itch in mice. Human skin samples from patients with atopic dermatitis also exhibited higher levels of S. aureus and V8 compared to healthy skin samples. The researchers found that V8 triggers itch by activating a protein called PAR1, which is present in skin neurons responsible for transmitting various signals like touch, heat, pain, and itch from the skin to the brain.
Interestingly, immune cells typically associated with itch, such as mast cells and basophils, did not contribute to itch after bacterial exposure. Additionally, inflammatory chemicals called interleukins and white cells, which are elevated in allergic reactions and skin diseases, did not play a role in itch induction.
To test whether an already approved anti-clotting drug that blocks PAR1 could alleviate itch, the researchers treated mice whose skin was exposed to S. aureus. The treatment resulted in rapid improvement, reducing the desire to scratch and minimizing skin damage. Furthermore, the mice no longer experienced abnormal itch in response to innocuous stimuli upon treatment.
The findings suggest that the PAR1 blocker, already used in humans to prevent blood clots, could be repurposed as an anti-itch medication. The active ingredient in the medication could potentially be the basis for the development of topical creams to alleviate itch.
The researchers plan to further explore whether other microbes besides S. aureus can trigger itch. There is evidence that various microorganisms, including fungi, viruses, and bacteria, are associated with itch, but the mechanisms are not yet understood.
The study also raises the question of why a microbe would cause itch in the first place. The researchers speculate that pathogens may exploit itch and other neural reflexes to their advantage. For example, it has been discovered that the tuberculosis bacterium directly activates neurons to cause coughing, potentially facilitating its spread between hosts.
The researchers believe that studying the itch-scratch cycle and its relationship to microbes could provide valuable insight into the benefit to both the microbe and the host. Further research in this area could uncover new therapeutic strategies and improve the management of chronic skin conditions associated with persistent itch.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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