“The discovery of why sunburn hurts could lead to new treatments for conditions like arthritis and cystitis,” reported The Daily Telegraph . The article said that scientists have identified a molecule that appears to cause sensitivity to pain from ultraviolet radiation, which could be a target for new pain treatments.
This was a laboratory study using rats and humans to identify certain molecules in cells that may play a role in regulating inflammatory pain such as sunburn. Scientists exposed the skin of 10 humans to UVB radiation to create a small patch of sunburn. At the peak of pain, two days later, researchers took biopsies of the affected skin and measured what gene activity there was in response to the sunburn. One molecule, called CXCL5, was found to be particularly active, indicating that it may play a role in sunburn-related pain. Similar results were found in rats.
These early findings are of interest, particularly because the results in humans were similar to those found in rats. Also, the researchers found that a molecule that blocks CXCL5 reduced pain-like behaviour in rats. Still, this is very early research and the importance of the findings for humans is uncertain. Any potential treatments are still a long way off.
The study was carried out by researchers from the University of London. The work is part of the Europain project and was funded by the Innovative Medicines Initiative Joint Undertaking. The study was published in the peer-reviewed journal Science Translational Medicine .
The media stories tended to overstate the potential of this research to lead to new pain treatments, and appear to have relied heavily on the press release for this study. The Daily Mail reported that a possible “lotion or potion” treatment based on an antibody to the molecule identified in this study is at present only theoretical and might be overly optimistic.
This was a laboratory study in which researchers tested their theory that certain molecules in human cells play an important and as yet unrecognised role in triggering inflammatory pain. They say that persistent pain is poorly treated at present, and that identifying key “mediators” of various types of pain could improve such therapies.
The researchers say that, during the inflammatory process, many molecules are released that induce and maintain pain sensations in the skin. Two types of molecules, cytokines and chemokines, are responsible for recruiting inflammatory immune cells to the injured tissue, triggering pain and tenderness.
They also say that most investigations into the different pain mechanisms to date have been in animal models, so the relevance of their findings to human pain is uncertain. By using both animals and human volunteers, the researchers thought they could increase the chances that any findings may be useful for humans.
The scientists recruited 10 healthy volunteers with similar skin types to the study. They all received the same measure of UVB radiation to a small patch of skin on the forearm, to create a small area of “sunburn”. At the peak pain threshold, which occurred within one or two days, researchers took a small biopsy from both irradiated and unirradiated skin. Using DNA technology, they analysed the tissue for changes in gene expression for more than 90 different molecules thought to be involved in the inflammatory process.
The researchers also used UVB rays to induce sunburn in the paws or shaved lower limbs of anaesthetised lab rats. Pain levels were measured in the rats, using standard behavioural measurements for pain, and tissue samples were taken for examination.
After measuring gene expression in humans, the researchers found that gene expression was greatest for one particular molecule, a chemokine called CXCL5. To examine the biology involved, they randomised rats into two groups, a treatment group and a control group. The treatment group rats were injected in their left hind paw with CXCL5 while the control group rats were injected with an inactive vehicle. The researchers wanted to see if this molecule produced a similar effect to UVB radiation in terms of pain-like behaviour.
To evaluate the effects of a CXCL5 antibody, the researchers gave other rats UVB irradiation to the left hind paw. They then allocated the rats to two groups and gave the treatment group an antibody to CXCL5 and the control group an inactive agent.
In both humans and rats, the expression of several genes that have previously been shown to contribute to pain sensitivity were significantly increased after UVB exposure. The researchers noted that:
The researchers say their data supports the notion that a group of molecules called chemokines are a promising and relatively unexplored group of “pain mediators”. Of particular interest was the CXCL5 molecule, which was previously unrecognised. They say that CXCL5 could become a target for medicines to treat inflammatory pain.
The researchers also say that they have shown that there was a similar gene expression in rats to humans, suggesting a similar underlying biological response, and that this finding could facilitate the development of new treatments.
This small and complex laboratory study is of interest in several ways. It has identified a molecule that appears to be important in the production of inflammatory pain caused by sunburn. It also found that the molecular processes underlying sensitivity to pain are similar in both humans and rats, which may make further investigations easier to translate into clinical practice.
It’s important to note that the researchers only looked at processes underlying the pain produced by sunburn and not other types of pain. However, they do point out that sunburn is a good example of inflammatory pain.
This is very early research looking at a specific pain process. Although the molecule identified appears to be key to the pain reaction and therefore merits further exploration, the role of the antibody in humans has not yet been tested. Any potential treatments based on targeting this molecule are still a way off and would need to go through extensive animal and clinical trials to look at safety and efficacy (how well the drug works) before they could be used.