Possible cure for sunburn and other pain discovered

Teresa Tanoos's picture
New study may lead to cure for sunburn and other pain
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If you’ve ever spent too much time in the sun, you know how painful it can be when, hours later, you find yourself suffering from red, blistery skin – better known as a sunburn, which a new study shows is caused by a molecule that is abundant in the skin’s epidermis.

The study found that blocking this molecule, called TRPV4, significantly protects the skin from the painful aftereffects of a sunburn. The finding, published in this week’s Proceedings of the National Academy of Sciences (PNAS) Early Edition online, resulted from research conducted in mouse models and human skin samples that could lead to new ways to prevent sunburn, as well as other sources of pain.

"We have uncovered a novel explanation for why sunburn hurts," said Wolfgang Liedtke, M.D., Ph.D., associate professor of neurology and neurobiology at Duke University School of Medicine and a lead author of the study.

“If we understand sunburn better, we can understand pain better because what plagues my patients day in and day out is what temporarily affects otherwise healthy people who suffer from sunburn,” added Liedtke.

Most sunburns are caused by ultraviolet B or UVB radiation, but these types of rays are also good for the body because they provide a daily dose of vitamin D and possibly improve mood. However, when people get too many UVB rays, they end up damaging the DNA in their skin cells; thus, increasing their risk of getting skin cancer. In this regard, sunburns are actually nature’s way of warning people to get out of the sun to avoid additional damage.

For this study, Liedtke collaborated with a team of researchers who investigated whether the TRPV4 molecule could play a role in the pain and tissue damage caused by UVB over-exposure. The molecule is plentiful in skin cells, and research shows it’s involved in other pain processes as well. As an ion channel, TRPV4 serves as a gateway in the cell membrane, which rapidly lets in positively charged ions like calcium and sodium.

To find out what role the molecule might play, the researchers built a mouse model without the TRPV4 molecule, but only in the cells of the epidermis, the outermost layer of the skin. They then took these genetically engineered mice and their normal counterparts and exposed their hind paws, which most resemble human skin, to UVB rays.

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As a result, the hind paws of the normal mice became hypersensitive and blistered from exposure to the UVB rays, whereas those of the mutant mice showed little sensitivity and tissue injury from UVB exposure.

The researchers then used cultured mouse skin cells to dissect the activities of the TRPV4 molecule, using a device showing that UVB caused calcium to flow into the skin cells, but only when the TRPV4 ion channel was present. Upon further molecular examination, the researchers also uncovered the entire sequence of events in this pathway, with each event affecting the next.

For example, they found that UVB exposure activates TRPV4, which in turn causes the influx of calcium ions, which then sendss in another molecule called endothelin that triggers TRPV4 to send more calcium into the cells. This other molecule, endothelin, is not only known to cause pain in humans, but it also induces itching, which may be why people with sunburns feel the urge to scratch their skin.

In order to test if these findings in mice and mouse cells have any human relevance, the research team used human skin samples to successfully demonstrate increased activation of TRPV4 and endothelin in the outside layer or epidermis of human skin following exposure to UVB rays.

To see whether they could block this novel pain pathway, the team then used a pharmaceutical compound called GSK205 that selectively inhibits TRPV4 and dissolved it into a solution of alcohol and glycerol before applying it to the hind paws of normal mice.

In so doing, the researchers found that the compound treated mice were, once again, mostly resistant to the pain and skin damaging effects of sunburn. Likewise, when researchers applied the compound to mouse skin cells in culture, they found that it stopped the UV-triggered influx of calcium ions into the cells.

“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 to treat chronic sun damage,” said Steinhoff, co-senior author of the study.

“I think we should be cautious because we want to see what inhibition of TRPV4 will do to other processes going on in the skin,” Liedtke added. “Once these concerns will be addressed, we will need to adapt TRPV4 blockers to make them more suitable for topical application. I could imagine it being mixed with traditional sunblock to provide stronger protections against UVB exposure.”

SOURCE: PNAS – PNAS-Plus, "UVB Radiation Generates Sunburn Pain and Affects Skin By Activating Epidermal TRPV4 and Triggering Endothelin-1 Signaling," Carlene Moore, Ferda Cevikbas, H. Amalia Pasolli, Yong Chen, Wei Kong, Cordula Kempkes, Puja Parekh, Suk Hee Lee, Nelly-Ange Kontchou, Iwei Ye, Nan Marie Jokerst, Elaine Fuchs, Martin Steinhoff, Wolfgang Liedtke (August 5, 2013)

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