"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." – Prof Stephen McMahon, King’s College London
Breakthrough research identifying the molecule responsible for making sunburn hurt (and an antibody that makes it stop hurting) has produced a juicy new target for development of therapies to treat inflammatory pain.
The molecule, known as “CXCL5,” is part of a family of proteins in the body called chemokines (responsible for issuing chemical ‘orders’), which recruit inflammatory immune cells to the injured tissue, triggering pain and tenderness.
The study, by a pain research team led by Prof Stephen McMahon and Dr. David Bennett at King’s College London, was the first to reveal this chemokine’s role in mediating pain. (See "CXCL5 Mediates UVB Irradiation-Induced Pain,” Jul 7, 2011, Science Translational Medicine.)
The study started by exposing patches of skin in healthy subjects to UVB irradiation, creating small areas of sunburn.
• The treated skin became tender over the following hours, with peak sensory change one to two days later. At this peak the researchers took small biopsies of the affected skin and analyzed the tissue for hundreds of pain mediators.
• They found that several of these mediators were over-expressed, 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 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,” Prof McMahon says. “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 [bladder pain].”
”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.”
Reversing the Animal-to-Human Research Paradigm
“Traditionally scientists have first studied the biology of diseases in animal models to identify mechanisms relevant to creating that state, but this often does not translate into effective treatments in the clinic,” Dr. Bennett points out.
“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.
“Improving healthcare by translating research more rapidly into clinical practice in this way is at the heart of our Academic Health Sciences Centre, King’s Health Partners.”
The research was funded by the Wellcome Trust (as part of the London Pain Consortium), and the Biotechnology and Biological Sciences Research Council.
Source: King’s College London press release, Jul 7, 2011