The red and irritated skin that forms the «badge» left on the body by prolonged exposure to the sun appears to be the result of the action of a molecule that is found in abundance in the skin, according to a new study.
Against different «sources» of pain
The blocking of this molecule called TRPV4 may protect against the painful effect of sunburn on the skin. These results, which involved mice as well as human skin samples, were published in the online edition of the journal «Proceedings of the National Academy of Sciences» and it is estimated that they can open the way to tackling both sunburns and other «sources» of pain.
"We have found a new explanation for why sunburn hurts," said Wolfgang Lindke, associate professor of neurology and neurobiology at Duke University School of Medicine and one of the study's lead authors. "If we understand sunburn better, we will understand pain better."
UVB radiation
The majority of sunburns are caused by ultraviolet B (UVB) radiation. Moderate exposure to this specific type of radiation is good for the body as it provides a dose of vitamin D and possibly acts as an antidepressant. However, extensive exposure to UVB radiation causes damage to the DNA of skin cells and increases the risk of cancer. Sunburns are essentially the «alarm bell» of nature to warn people that they must stop exposure to solar radiation.
Professor Linke collaborated with an international team of researchers to investigate whether the molecule TRPV4, which is abundantly found in skin cells and has been shown to be involved in other processes related to pain, may play a role in pain and in tissue destruction caused by UVB overexposure. TRPV4 is an ion channel, a gate in the cell membrane that allows positively charged ions such as calcium and sodium to enter the cell.
The experiments
Initially, the researchers created a mouse model that exhibited a lack of TRPV4 only in the skin cells. They then exposed the foot skin of both genetically modified mice and normal mice to UVB radiation. As a result, the skin of the normal mice became hypersensitive and developed blisters after UVB exposure, whereas the skin of the genetically modified mice showed minimal sensitivity to ultraviolet radiation.
Subsequently, the scientists cultured mouse skin cells in the lab in order to discover the precise properties of TRPV4. Using a device developed by specialists from the Pratt School of Engineering at DeWitt University, they showed that UVB radiation induces sodium influx into the skin cells, but only when TRPV4 is present.
Further molecular analyses revealed the entire «chain» of events: UVB radiation activates TRPV4, which causes an influx of calcium ions, leading to the release of another molecule called endothelin which in turn causes TRPV4 to send more calcium into the cells. Endothelin is known to cause pain and itching in humans, which explains the intense itching sensation experienced by individuals with sunburn.
After the mice, experiments on human skin cells followed to see if the previous findings could be verified. Increased activation of TRPV4 and endothelin was demonstrated in human skin cells after exposure to UVB ultraviolet radiation.
New therapeutic target
The scientists, however, went one step further trying to block this pain pathway. They used a compound with the code name GSK205 which selectively inhibits TRPV4. They introduced the compound into a solution of alcohol and glycerol – essentially a skin antiseptic – and applied the solution to the feet of normal mice. They discovered that the experimental animals on which the solution was applied became again resistant to pain and the itching sensation caused by sunburn. When the pharmaceutical compound was administered to mouse skin cells that were in culture it appeared to stop the influx of calcium ions into the cells.
"The findings suggest that TRPV4 may be a new target for the prevention and treatment of sunburn and possibly chronic skin damage due to sun exposure, including skin cancer and photoaging. However, further research is needed before TRPV4 inhibitors can add to our arsenal against harmful sun radiation. For example, they could be used in skin creams to treat chronic sun damage," the researchers note.
However, Dr. Lindke stressed that we must be careful as we do not know what TRPV4 inhibition may cause in other processes that take place in the skin. "When we have evidence in our hands that will testify to the safety of the procedure, we should adapt TRPV4 inhibitors so that they are suitable for topical application. I imagine, for example, that they could be introduced into classic sunscreen to offer stronger protection against UVB radiation," the expert concluded.
