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 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,” says 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 says, “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 adds, “starting with candidates that by definition are relevant
to human chronic pain states.”
“UVB Irradiation as a Translational Pain Model Reveals CXCL5 as a Pain Mediator”
