Steve McMahon at Kings College London and colleagues used ultraviolet-B radiation to burn a small patch of skin in rats and 10 healthy humans. They then took skin biopsies and screened them for molecules involved in the inflammatory response.
In both rats and humans, the molecule that was most overexpressed after UV exposure was a protein called CXCL5 – a so-called chemokine molecule. Although CXCL5 is known to be involved in inflammation, "there is no previous literature suggesting it has anything to do with pain", says McMahon.
To verify the role of CXCL5 in inflammatory pain, McMahon's team injected the molecule into healthy rats without exposing them to UV. When they then tested the rats' pain thresholds, they were similar to those typical of sunburn. This sensitivity was reversed by an antibody known to neutralise the molecule.
Sunburn is one of a number of pain conditions caused by the body's inflammatory response. UV damage to the skin causes the immune system to recruit numerous signalling molecules – such as chemokines – and immune cells to fight infection. Together, these can activate nerve fibres and cause pain long after the sun sets. Inflammatory pain also causes more long-lasting chronic pain conditions, such as arthritis.
Neutralising these pain mediators could be an effective way to treat chronic pain directly, says McMahon – although it is unclear how many such pain mediators are involved in the pain response more generally. "Is there one and we can all go home, or is there going to be one for every disease state? I think the answer is going to be somewhere in between," he says.
McMahon now plans to screen tissues from people with a range of conditions, from painful bladder syndrome to chronic tendonitis, to see whether similar molecules are responsible.
Most drug discovery research starts with animal models that often don't hold up in human trials. Ru-Rong Ji, who studies chronic pain at Brigham & Women's Hospital in Boston, Massachusetts, thinks that because the findings are consistent in both humans and animals, they should be easier to translate to the clinic. "This is a very significant study," he says.
Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.3002193