Many a summer vacationer has brought back an unwelcome souvenir from a trip to the beach: a painful, red sunburn. But now scientists think they’ve found a way to wipe that pain – and redness – away.
Duke University neurologist Wolfgang Liedtke and colleagues from Rockefeller University and the University of California San Francisco have found that blocking a single molecule called TRPV4 can plug the pain pathway. They described their research in the Proceedings of the National Academy of Sciences this week. The upshot is, if TRPV4 blockers can be combined with regular sunblock, sunbathers might be able to escape pain, injury, and an appearance resembling a boiled lobster.
“This channel is the ultimate molecule” mediating the pain and tissue injuries associated with sunburn, Liedtke said in a phone interview. “It opens the gate, and calcium comes in.”
Once calcium cascades into the cell, it causes the influx of another molecule called endothelin, which is likely responsible for that itchy feeling you get after a sunburn. Shutting the gate closed, could prevent that pain cascade from taking place.
In their experiments, Liedtke and his colleagues created mice that lacked functional TRPV4 in the cells of their epidermis the outermost layer of the skin. When they exposed the feet of the altered mice to UV-B rays – the component of sunlight implicated most heavily in sunburn injury – they were much less sensitized and damaged than the feet of the normal mice. In a later experiment, when the scientists applied a solution containing a pharmaceutical compound that inhibits TRPV4 to the feet of unaltered mice, they didn’t roast under the UV rays either.
It remains to be seen whether blocking TRPV4 could help protect against the damage wrought by UV-B rays on DNA, which can hike up a person’s susceptibility to cancer. If the influx of calcium through the TRPV4 channel is essential for the body’s natural DNA repair mechanisms, inhibiting the channel would be a bad thing; but, if calcium interferes with that repair work, TRPV4 could be a powerful assistant. More research is needed.
Several pharmaceutical companies already have TRPV4 blockers in production. Blocking the channel may lessen the risk of edema, or fluid leakage from the lungs, in people that have suffered heart failure, according to a 2012 paper from GlaxoSmithKline scientists published in Science Translational Medicine. TRPV4 inhibition is also a promising treatment for overactive bladder. Because the components are already identified, getting a commercial sunscreen with TRPV4 blockers to market could only take a matter of a few years, Liedtke estimates.
Combining TRPV4 blockers with traditional sunscreen would be essential, since the reddening and pain of a sunburn is a natural alarm system that alerts a person to potentially harmful levels of sun exposure. Avoiding the pain of sunburn doesn't necessarily mean a person's immune to harmful effects from the sun. Liedtke thinks that as long as people take the appropriate precautions of protecting themselves from UV rays, there will likely be no harm in making it easier for people to avoid sunburn.
Not only does the discovery point towards an even stronger sunburn protectant, it also suggests that our skin cells are much more active than we might appreciate, Liedtke says. The way UV-B radiation is sensed in the epidermis bears some resemblance to how the light-sensitive cells in our retinas act.
In both the retina and the epidermis, “light is translated into language the cell can speak,” Liedtke says.
Liedtke’s path to this discovery began in 2000, when he and colleagues at Rockefeller wrote one of the first papers on the TRPV4 molecule. Since then, he’s been working to unravel its secrets. He admits it’s a bit out of the ordinary for a neuroscientist to be so deeply involved in looking at skin, but as this work shows, the skin cell is more than just part of a barrier against the elements: it can moonlight as a sensory organ, and an immune system foot soldier. Pain isn’t just in the brain.
“When we look above the rim of the usual mousehole we’re in, that’s when things get interesting,” he said.
SOURCE: Moore et al. “UVB Radiation Generates Sunburn Pain and Affects Skin By Activating Epidermal TRPV4 and Triggering Endothelin-1 Signaling.” Proceedings of the National Academy of Sciences published online 5 August 2013.