Harvard Researchers Unravel the Enduring Mystery of Itch
Harvard Medical School researchers have made a groundbreaking discovery, revealing that the skin bacterium Staphylococcus aureus can directly induce itching by interacting with nerve cells. The study, published in the journal Cell and based on experiments with mice and human cells, provides crucial insights into the longstanding puzzle of itchiness.
The research explains why persistent itching is often associated with skin disorders like eczema and atopic dermatitis. In these conditions, the imbalance of skin microorganisms allows S. aureus to thrive, challenging the previous belief that itchiness in these disorders resulted from skin inflammation.
Unraveling the Itch-Inducing Mechanism of S. aureus and Potential Treatment Breakthroughs
The study identified a novel mechanism, showing that S. aureus independently causes itch by initiating a molecular chain reaction leading to the urge to scratch. Senior author Isaac Chiu noted that this discovery could pave the way for new treatments, as experiments demonstrated that an FDA-approved anti-clotting medicine successfully interrupted the itch-scratch cycle, relieving symptoms and minimizing skin damage.
The results have the potential to guide the development of oral medications and topical creams for addressing persistent itch associated with various conditions linked to an imbalance in the skin microbiome, such as atopic dermatitis, prurigo nodularis, and psoriasis.
The frequent scratching characteristic of these conditions can lead to skin damage and intensify inflammation.
“For individuals dealing with chronic skin conditions, itch can be highly incapacitating. It’s noteworthy that many of these patients harbor on their skin the very microorganism we’ve demonstrated, for the first time, can trigger itch,” explained Liwen Deng, the first author of the study and a postdoctoral research fellow in the Chiu Lab.
V8’s Activation of PAR1 in Skin Neurons
The analysis revealed that V8 induces itch by activating a protein known as PAR1, present on skin neurons originating in the spinal cord, responsible for transmitting various signals like touch, heat, pain, and itch from the skin to the brain. Under normal circumstances, PAR1 remains inactive, but upon contact with specific enzymes, including V8, it becomes activated. The study demonstrated that V8 precisely cleaves one end of the PAR1 protein, awakening it. Experiments in mice demonstrated that once activated, PAR1 initiates a signal interpreted by the brain as an itch. When the experiments were replicated using lab dishes containing human neurons, they also responded to V8.
Interestingly, the experiments indicated that exposure to bacteria did not prompt the itch-inducing activity typically associated with immune cells related to skin allergies, such as mast cells and basophils. Furthermore, inflammatory chemicals like interleukins and white cells, activated during allergic reactions and often elevated in skin diseases and certain neurological disorders, did not play a role in triggering itch.
Liwen Deng remarked, “When we initiated the study, it was unclear whether the itch was a result of inflammation or not. We show that these factors can be separated, indicating that inflammation is not a prerequisite for the microbe to induce itch, although the itch does exacerbate skin inflammation.”
Breaking the Itch-Scratch Cycle
Given that PAR1, the protein activated by S. aureus, plays a role in blood clotting, researchers sought to determine whether an already approved anti-clotting drug that inhibits PAR1 could alleviate itch. Indeed, it did.
Mice experiencing itchiness due to S. aureus exposure exhibited rapid improvement when treated with the anti-clotting drug. Their inclination to scratch significantly diminished, along with the reduction in skin damage caused by scratching.
Furthermore, after receiving PAR1 blockers, the mice no longer displayed abnormal itch in response to harmless stimuli.
The PAR1 blocker, already utilized in humans to prevent blood clots, holds promise for repurposing as an anti-itch medication. The researchers suggest that the active ingredient in the drug could serve as the foundation for topical creams targeting itch.
A pressing question for future research is whether microbes other than S. aureus can also instigate itch
“We know that many microbes, including fungi, viruses, and bacteria, are associated with itch, but how they induce itch remains unclear,” noted Chiu.
Additionally, the study prompts a broader inquiry: Why would a microbe induce itch? From an evolutionary standpoint, what benefits does the bacterium gain?
One speculation is that pathogens might exploit itch and other neural reflexes for their advantage. For instance, prior research has demonstrated that the TB bacterium directly activates vagal neurons to induce coughing, potentially facilitating its spread from one host to another.
Deng remarked, “It’s a speculation at this point, but the itch-scratch cycle could benefit the microbes and enable their spread to distant body sites and to uninfected hosts. Why do we itch and scratch? Does it help us, or does it help the microbe? That’s something that we could follow up on in the future.”
Read the original article on: ScitechDaily
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