Sunburn offers clues for pain drug development

Scientists have found a molecule in the body which controls sensitivity to pain from UVB irradiation, or sunburn, and say it may help them develop new drugs to treat pain in other common conditions such as arthritis.

The CXCL5 molecule is part of a family of proteins called chemokines which recruit inflammatory immune cells to injured tissue, triggering pain and tenderness, the researchers said in a study in the journal Science Translational Medicine.

"We've identified this chemokine as an important factor that drives some forms of pain, and we did that in the context of UVB irradiation or sunburn," said Stephen McMahon from the Wolfson Center for age-related diseases at King's College London and head of a research group called the London Pain Consortium.

"But this study isn't just about sunburn. More broadly we have identified a mediator that may be important in a variety of different pains states - particularly those associated with inflammation - and there are lots of those out there, for example in arthritis," he said in a telephone interview.

UVB radiation typically affects the outer layer of skin, the epidermis, and is the primary agent responsible for sunburn.

McMahon and colleague David Bennett, also of King's College London, recruited health volunteers and exposed patches of their skin to UVB irradiation, creating a small area of sunburn.

The affected skin became tender over the following hours and the pain grew to a peak roughly one to two days later. At this peak the researchers took small biopsies of the affected skin and searched the tissue for hundreds of pain mediators.

They found high levels of several of these mediators, including CXCL5, so they then examined the biology of these factors in rats to find out whether they were likely to be responsible for driving the pain in the sunburnt skin.

Their results showed that CXCL5 was present at high levels in the human biopsies and in the biology of the chemokine protein in rats - suggesting it is responsible for a significant amount of the pain in the sunburn. Further tests on the rats showed that a neutralizing antibody which targeted CXCL5 was able to reduce the sensitivity to pain caused by the UVB irradiation.

McMahon said the next step would be to develop a human version of the antibody for testing in clinical trials.

Several major drugmakers, including Pfizer, AstraZeneca and GlaxoSmithKline, have drug research programs looking at chemokines and McMahon said there were likely to be candidate compounds that could be tested in human trials fairly swiftly.

"Giving an antibody is quite an attractive treatment strategy, because even though you have to inject it... the antibody then often hangs around for weeks, and it almost totally blocks the availability of the factors it binds to," McMahon explained.