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We're a Whole Lot Closer to a Cure for Itching

Scientists say skin is more than just a barrier to the outside world, a realization that could lead to the end of itching.

Whether it's the result of a mosquito bite, an allergic reaction, or dry skin, few sensations are quite as irritating as the itch. There are dozens of causes of itchiness, yet despite its banality it remains notoriously difficult to classify its cellular mechanisms of action, and as a result, treat. But thanks to new research coming out of Duke University, we're closer than ever to developing a cure for the itch.

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Technically, an itch is just defined as the sensation which results in the reflex to scratch. Some have likened it to pain, and while both pain and itchiness are unpleasant sensations, they result in opposite responses: a painful area will result in a withdrawal reflex whereas itching leads to scratching. Moreover, pain and itchiness are apparently antagonistic insofar as scratching is seen as a method of inflicting pain to relieve itchiness.

Beyond these simplistic classification attempts, scientists have had a tough time determining what causes itchiness to occur on a cellular level. Recently, a team of researchers led by Wolfgang Liedtke, a professor of neurology, neurobiology and anesthesiology at Duke University, brought us significantly closer to a cure for the short-term itch by detailing how an ion channel protein in found abundantly in skin cells plays a significant role in causing the sensation.

In a paper published last week in the Journal of Biological Chemistry, Liedtke and his team followed up their earlier research in which they found that TRPV4, the aforementioned ion channel protein in skin cells, played a critical role in conveying feelings of pain caused from overexposure to UV rays (think sunburn) to the brain. In that study, Liedtke and his colleagues found that ultraviolet radiation activated TRPV4 in the skin cells, causing them to release a molecule called endothelin-1, which has been linked to burning and itching sensations.

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In its most recent paper, the Duke team found that TRPV4 was also intimately linked to feelings of itchiness after exposing genetically-engineered mice in which the TRPV4 protein had been dialed back to chemicals known to cause itchiness.

Remarkably, the team found that those mice with reduced TRPV4 sensitivity were less liable to scratch themselves when exposed to the chemicals, suggesting that TRPV4 plays a critical role in conveying the sensation of itchiness to the brain. More importantly, by isolating this particular protein as the gateway to the molecular path that ultimately leads to reflexive scratching, the team hopes that this will allow for the production of drugs which lower sensitivity to sensations of itchiness.

"This study is exciting for basic science but also from the translational-medical side. It means that [short-term] itch is something we can rationally treat," said Liedtke in a press release. "We can now envision developing topical treatments for the skin that target specific molecular pathways to suppress itch and inflammation."

Moreover, these findings also change the way the researchers are thinking about the body's largest organ, the skin. Previously assumed to be little more than a barrier to the outside world, these findings suggest that the skin has significant sensory capabilities, which could lead to further medicinal breakthroughs for skin conditions.

"For many decades, skin was believed to be a mere barrier, not endowed with sensory capability," Yong Chen, a co-author of the study, said in a statement. "Now it turns out skin has features reminiscent of sensory-neural cells that are instrumental in facilitating the sensation of itch."

Since TRPV4 is present on the surface of skin cells, TRPV4-suppressant itch remedies will likely appear in the form of topically-applied ointments. Liedtke has already begun testing the efficacy of such ointments with researchers at Duke's Department of Dermatology and so far the results have corroborated Liedtke's and his team's findings. In the meantime, Liedtke hopes to probe deeper into the nature of cell-to-cell interactions in the skin, which will lead to improvements in personalized medicine and possible solutions for generalized long term itchiness.