Scientists think they have found a way to prevent the painful, red skin that comes from too much time in the sun. They report that the pain is caused by a molecule in the skin’s epidermis.

Blocking this molecule, known as TRPV4, protects against sunburn pain, say the researchers, whose work is published this week in the Proceedings of the National Academy of Sciences, Early Edition online. The study, which was conducted in mouse models and human skin samples, could yield a way to combat sunburn and possibly several other causes of pain, note the investigators.

Wolfgang Liedtke, M.D., Ph.D., one of the senior authors of the study and associate professor of neurology and neurobiology at Duke University School of Medicine, worked with a multi-institutional team of researchers: Elaine Fuchs, Ph.D., professor at Rockefeller University and an investigator with the Howard Hughes Medical Institute, and Martin Steinhoff, M.D., Ph.D., professor of dermatology and surgery at the University of California, San Francisco. They investigated whether the TRPV4 molecule, which is abundant in skin cells and has been shown to be involved in other pain processes, might play a role in the pain and tissue damage caused by UVB overexposure. TRPV4 is an ion channel, a gateway in the cell membrane that allows the rapid entry of positively charged ions such as calcium and sodium.

First, the researchers built a mouse model that was missing TRPV4 only in the cells of the epidermis, the outermost layer of the skin. They took these genetically engineered mice and their normal counterparts and exposed their hind paws, which most resemble human skin, to UVB rays. The hind paws of the normal mice became hypersensitive and blistered in response to the UVB exposure, while those of the mutant mice showed little sensitization and tissue injury.

Next, they used cultured mouse skin cells to dissect the activities of TRPV4. Using a device engineered by Nan Marie Jokerst, Ph.D., a professor of electrical and computer engineering at Duke’s Pratt School of Engineering, the researchers showed that UVB caused calcium to flow into the skin cells, but only when the TRPV4 ion channel was present.

Further molecular analysis uncovered the entire sequence of events in this pathway, with each event affecting the next: UVB exposure activates TRPV4, which causes the influx of calcium ions, which brings in another molecule, endothelin, which triggers TRPV4 to send more calcium into the cells. Endothelin is known to cause pain in humans and also evokes itching, which could explain the urge that sunburned patients feel to scratch their skin.

To test whether these findings in mice and mouse cells have human relevance, the researchers used human skin samples to successfully demonstrate increased activation of TRPV4 and endothelin in human epidermis after UVB exposure.

“The results position TRPV4 as a new target for preventing and treating sunburn, and probably chronic sun damage including skin cancer or skin photo-aging, though more work must be done before TRPV4 inhibitors can become part of the sun-defense arsenal, perhaps in new kinds of skin cream, or in treating chronic sun damage,” said Dr. Steinhoff, co-senior author of the study.

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