KING’S COLLEGE LONDON (UK) — Discovery of a molecule that controls sensitivity to pain from UV rays may lead to medicines that cool a sunburn’s sting and control other inflammatory conditions like arthritis.
The study, published in the journal Science Translational Medicine, is the first to reveal the role of the CXCL5 molecule in mediating pain. The molecule is part of a family of proteins called chemokines, which recruit inflammatory immune cells to injured tissue, triggering pain and tenderness.
The CXCL5 molecule recruits inflammatory immune cells to injured tissue, triggering pain and tenderness. (Credit: King’s College London)
For the study, volunteers’ had healthy patches of skin exposed to UVB irradiation, creating a small area of sunburn. The treated skin became tender over the following hours, with peak sensory change one to two days later. At the peak researchers took small biopsies of the affected skin and analyzed the tissue for hundreds of pain mediators.
Several of these mediators were over-expressed, and researchers 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 sunburned skin.
The mediator CXCL5 was significantly over-expressed in the human biopsies and the biology of this chemokine in rats, which suggests it is responsible for a significant amount of sensitivity in the sunburn.
Further tests carried out on the rats showed that a neutralizing antibody targeting CXCL5 significantly reduced the sensitivity to pain caused by the UVB irradiation.
“These findings have shown for the first time the important role of this particular molecule in controlling pain from exposure to UVB irradiation,” says Steve McMahon, professor at King’s College London.
“But this study isn’t just about sunburn—we hope that we have identified a potential target which can be utilized to understand more about pain in other inflammatory conditions like arthritis and cystitis. I’m excited about where these findings could take us in terms of eventually developing a new type of analgesic for people who suffer from chronic pain.”
Not only are the findings of importance for understanding the causes of pain, but the approach they used by first identifying the mechanisms in humans and then looking at these in pre-clinical animal models is a novel one in the field of pain research.
“Traditionally scientists have first studied the biology of diseases in animal models to identify mechanisms relevant to creating that state,” says David Bennett, clinical scientist. “But this often does not translate into effective treatments in the clinic.
“What we have done is reverse this traditional method by identifying putative mediators in humans first, and then exploring this further in rats. This enabled us to see that the rats’ response to these pain mediators closely parallel those occurring in humans and identify mechanisms of action in the preclinical studies.
‘”We intend to extend this approach to other types of pain and in particular to study patients suffering from chronic pain with the hope that this will speed up the process of turning science into effective treatments for patients.”
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