Scientists have identified a molecule in the skin’s epidermis called TRPV4 that causes the pain we feel from a sunburn. By identifying and inhibiting it, the researchers may have found a way to block the pain.
The research, published online in the journal Proceedings of the National Academy of Sciences, involved studies conducted with both mouse models and human skin samples.
A team, led by Dr. Wolfgang Liedtke from Duke University School of Medicine, looked at whether TRPV4 – a “gateway” in the cell membrane that allows in positively charged calcium and sodium ions – could be involved in the pain and tissue damage from long-term UVB exposure.
To conduct their study, the researchers built a mouse model with an epidermis that was missing TRPV4. These engineered mice, along with a group of normal control mice, then had their hind paws exposed to UVB rays. Researchers chose the hind paws because it is the area most similar to human skin.
The researchers noticed that the normal mice blistered and were hypersensitive as a result of the UVB, but the engineered mice without TRPV4 displayed very little sensitivity or tissue injury.
Following their observations, Dr. Liedtke and his team analyzed the activities of the molecule and found that UVB caused calcium to flood into the skin cells, but only in the presence of TRPV4. Furthermore, they found a circular chain of events that follows from UVB exposure:
- UVB exposure activates TRPV4
- TRPV4 causes the inpouring of calcium ions
- The calcium ions bring in another molecule called endothelin (which causes pain and itching in humans)
- Endothelin triggers TRPV4 to send more calcium to the cells.
The team then used human skin samples to test whether the mice findings have human relevance, and they found that increased TRPV4 activity and endothelin activation also occurs in the human epidermis after exposure to UVB.
Dr. Liedtke says:
“We have uncovered a novel explanation for why sunburn hurts.
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.”
To try and block the pain associated with sunburns, the researchers used a compound called GSK205, which specifically inhibits TRPV4. When they treated the hind paws of the normal mice, they found that they were resistant to the painful skin effects of sunburn.
They also found that the compound stopped the inpouring of calcium ions into the skin cells, stopping the chain of events that leads to pain.
Dr. Martin Steinhoff, co-author of the study from the University of California-San Francisco, says:
“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.”
But he notes that more work must be done before the inhibitors can be incorporated into skin creams for protection, or before they can be used to treat the damaging effects of the sun.
Dr. Liedtke adds that he thinks “we should be cautious because we want to see what inhibition of TRPV4 will do to other processes going on in the skin.”