For those of you who hit the beach this past holiday weekend, and still have those angry tan lines… researchers have discovered the molecule responsible for your pain.
Called CXCL5, the molecule triggers inflammations caused by UVB rays by activating nerve fibers to cause pain and tenderness. The findings could lead to drugs that block its activity, reducing the pain of that sunburnt sear.
- They first irradiated small patches of skin on people’s arms and rats’ paws, and then took samples of the sunburned skin.
- After screening the tissue for 100s of pain mediators, they found that CXCL5 is dramatically overexpressed in both humans and rats. This molecule is known to be involved in inflammation, but “there is no previous literature suggesting it has anything to do with pain,” says McMahon.
- For rats in particular, CXCL5 is the most elevated at times of max pain, and injecting it into healthy, unexposed rat skin caused hypersensitivity.
They found that part of CXCL5’s pain-causing power is due to its ability to recruit inflammatory immune cells to the injury site. (Pictured, immune cells infiltrate CXCL5 treated skin.) Those cells secrete pain-sensitizing molecules, which act on our sensory nerve fibers, causing pain for days.
And! They also found that in rats, the pain caused by UVB rays can be eliminated with an antibody known to target and neutralize CXCL5.
And! Since the findings were consistent in both humans and animals, they should be easier to translate to the clinic. (They even looked at humans first and used animals as follow-up: “It’s the exact opposite of the normal process of trying to do science in drug discovery,” McMahon says.)
Sunburns are the body’s response to ultraviolet radiation, which kills some skin cells and permanently damages the DNA of others, sometimes leading to skin cancer later on. In an attempt to save the damaged cells with oxygen and nutrients, the body pumps more blood to the skin, turning it red. And the swollen blood vessels ooze plasma, causing blisters.
“I’m excited about where these findings could take us in terms of eventually developing a new type of analgesic for people who suffer from chronic pain,” McMahon says.
He plans to screen tissues from people with conditions ranging from painful bladder syndrome to chronic tendonitis, to see whether similar molecules are responsible. Neutralizing these pain mediators could be an effective way to treat chronic pain directly.
The study was published in Science Translational Medicine today.
Image: King’s College London