Researchers have discovered a molecule responsible for triggering the inflammatory pain of sunburn caused by the sun’s UVB rays, reports a new study in the 6 July issue of Science Translational Medicine.
The molecule—part of a family of proteins called chemokines—works by activating nerve fibers to cause pain and tenderness. The findings could lead to drugs that block the activity of this molecule, called CXCL5, to reduce or stop pain in sunburned skin.
“This finding might be indicative of a more general role of CXCL5 in a variety of clinically relevant inflammatory pain states, for instance osteoarthritis or cystitis,” said Stephen McMahon, senior author of the paper and professor of physiology at King’s College London.
CXCL5 provides a lead that researchers can follow to other pain mediators responsible for a variety of chronic inflammatory pain conditions, which currently affect 1 in 5 people in the Western world.
UVB rays from the sun are the main cause of sunburn pain, although UVB and UVA rays both contribute to skin cancer. In the study, McMahon and colleagues took small samples of sunburned human skin and screened the tissue for pain mediators. They found that CXCL5 in particular was dramatically overexpressed in sunburned human skin. Higher levels of CXCL5 were also seen in the skin of sunburned rats.
Not only was CXCL5 most elevated at the time of maximum pain in the rats, its injection into healthy rat skin caused hypersensitivity. Some of CXCL5’s pain-causing effects are due to its ability to recruit inflammatory immune cells called neutrophils and macrophages, the researchers found. These immune cells presumably secrete CXCL5 and other pain-sensitizing molecules, which act on sensory nerve fibers.
Encouragingly, the researchers showed in rats that pain caused by UVB rays can be eliminated with a neutralizing antibody targeting CXCL5.
The results provide new insights into the role of chemokines in persistent pain states. In an ongoing quest to identify these proteins in other conditions such as chronic bladder inflammation, for example, the team is currently collecting biopsy specimens from chronic pain patients to see if they can pinpoint pain mediators in these conditions.
“The real reason we did this experiment was an attempt to do biomedical research and drug discovery in a new way,” McMahon said, “that is, to start with human biopsy specimens from the disease or pain state, identify potential mediators here, and then test the mechanism of action of these putative mediators in pre-clinical experiments.”
“We think this might be a way of improving the drug discovery process,” McMahon added, “starting with candidates that by definition are relevant to human chronic pain states.”
Read the report, “UVB Irradiation as a Translational Pain Model Reveals CXCL5 as a Pain Mediator” by Stephen McMahon and colleagues.
Visit Science Translational Medicine.