Sunburn Pain Discovery Could Benefit Inflammation Conditions
There aren't many drugs that work effectively against pain that persists for hours and days, and those that do, don't always give full relief. Also, their prolonged use can result in severe side effects, so finding out more about the chemicals behind pain in the body could be helpful to improving treatments in this field, said the researchers.
Senior author Dr Stephen McMahon, a professor of physiology at King's College London, and colleagues, had a hunch they might find some clues by looking for undiscovered cytokines and chemokines that might be involved in inflammatory pain.
Cytokines and chemokine are "mini-proteins" produced by cells in the immune system. They help regulate immune responses to infection and injury such as inflammation and wound healing.
McMahon and his team used ultraviolet B (UVB) light to induce persistent pain in small patches of skin on humans and rats. (Although UVB and UVA rays both contribute to skin cancer, it is UVB rays that mainly cause sunburn pain.)
Using "custom-made polymerase chain reaction arrays" they analyzed samples from the skin patches taken at time of maximum pain and found over 90 different pain-mediating chemicals. They wrote that there was a "significant positive correlation in the overall expression profiles" between the rats and the humans.
In particular they found significantly increased expression of several genes known to contribute to pain hypersensitivity, and irregular activity in several chemokines.
Among the genes, CXCL5 appeared to be the most affected by UVB treatment in human skin, and when they injected it into the skin of rats, the researchers found it triggered the same "mechanical hypersensitivity caused by UVB irradiation". This hypersensitivity was accompanied by an increase in neutrophils and macrophages, types of inflammatory white blood cell, in the skin tissue.
When McMahon and his team switched off the effect of CXCL5, this reduced the abnormal pain-like response.
They concluded that:
"Our findings demonstrate that the chemokine CXCL5 is a peripheral mediator of UVB-induced inflammatory pain, likely in humans as well as rats."
McMahon told the press that:
"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."
About 1 in 5 people in the Western world suffers from chronic inflammatory pain. The researchers hope that their discovery will help the development of new pain-killing drugs, perhaps along the lines of an antibody that neutralizes CXCL5.
The team is also looking at other roles that chemokines might play in persistent pain states. For instance, they are collecting biopsy samples from patients with chronic bladder inflammation to find out which chemokines might be mediating the pain.
"The real reason we did this experiment was an attempt to do biomedical research and drug discovery in a new way."
He explained that means starting with human samples from the particular disease or painful condition, finding likely candidates that could be mediating the pain, then testing their action in experiments, much as they have done in this study.
Thus by "starting with candidates that by definition are relevant to human chronic pain states", they could establish a way to improve the drug discovery process, he added.
CXCL5 Mediates UVB Irradiation-Induced Pain."
John M. Dawes, Margarita Calvo1, James R. Perkins, Kathryn J. Paterson, Hannes Kiesewetter, Carl Hobbs, Timothy K. Y. Kaan, Christine Orengo, David L. H. Bennett, Stephen B. McMahon.
Sci Transl Med 6 July 2011: Vol. 3, Issue 90, p. 90ra60
Additional source : American Association for the Advancement of Science.
Written by Catharine Paddock PhD
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