Scientists from Duke University in North Carolina say that blocking this molecule, called TRPV4, greatly protects against the painful effects of sunburn, having conducted research published in Proceedings of the National Academy of Sciences (PNAS) Early Edition online, that could yield a way to combat sunburn and possibly several other causes of pain.
"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," says Wolfgang Liedtke, M.D., Ph.D., one of the senior authors of the study.
The vast majority of sunburns are caused by ultraviolet B or UVB radiation; which, in moderation, does the body good, giving a daily dose of vitamin D and perhaps improving mood.
However, if people get too much, it can damage the DNA in their skin cells and increase their susceptibility to cancer. Sunburn is body’s natural way of telling people to avoid further damage.
The researchers, comprising Liedtke, Elaine Fuchs, Ph.D., a professor at Rockefeller University and Martin Steinhoff, M.D., Ph.D., professor of dermatology and surgery at the University of California, investigated whether the TRPV4 molecule, which is abundant in skin cells, might play a role in the pain and tissue damage caused by UVB over-exposure.
TRPV4 is an ion channel, a gateway in the cell membrane that rapidly lets in positively charged ions such as calcium and sodium.
"The results [of the study] 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," says Steinhoff.
"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 adds.
"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."
The team exposed mouse models that were missing TRPV4 to UVB rays and compared them to ‘normal’ mice; and found that whilst the latter became hypersensitive and blistered in response to the UVB exposure, the mutant mice showed little sensitization and tissue injury
Next, they used cultured mouse skin cells to dissect the activities of TRPV4, showing 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 called endothelin, which triggers TRPV4 to send more calcium into the cells.
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, before using a pharmaceutical compound, GSK205, to see if they could block the novel pain pathway.
They found that the mice treated with the compound were again largely resistant to the pain-inducing and skin-disrupting effects of sunburn.