Gene that encodes crucial pain receptor may be key to individualizing therapy for major health problem
Nearly one in five people suffer from the insidious and often devastating problem of chronic pain.
That the problem persists and is growing, is striking given the many breakthroughs in understanding the basic biology of pain over the past two decades. A major challenge for treating chronic pain is to understand why certain people develop pain while others, with apparently similar disorders or injuries, do not. An equally important challenge is to develop individualized therapies that will be effective in specific patient populations.
Research published online in Nature Medicine points to solutions to both challenges. A research team led by Prof. Jeffrey Mogil of McGill University in Montreal and Prof. Michael Salter of The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, has identified a major gene affecting chronic pain sensitivity. The findings also suggest a new approach to individualizing treatment of chronic pain.
The gene that the researchers identified encodes the pain receptor known as P2X7. Specifically, the scientists discovered that a single amino-acid change in P2X7 controls sensitivity to the two main causes of chronic pain: inflammation and nerve damage.
The amino-acid change is known to affect only one function of P2X7 receptors - the forming of pores that permit large molecules to pass through - while leaving intact the other function, of allowing much tinier ions to flow through. Using a peptide that targets pore formation only, the researchers found that pain behaviours were dramatically reduced.
The scientists then examined genetic differences among human patients suffering from two distinct types of persistent pain: chronic post-mastectomy pain and osteoarthritis. In both cases, they found that individuals with genetically inherited low pore formation in P2X7 receptors experienced lower pain levels.
"Our findings indicate that it may be possible to develop drugs that block pores in this crucial receptor, while leaving its other function intact - thereby killing pain while minimizing side effects," said Prof. Mogil, E.P. Taylor Professor of Pain Research in McGill's Department of Psychology.
Prof. Salter, Anne and Max Tanenbaum Chair in Molecular Medicine at SickKids, said these discoveries "point toward a new strategy for individualizing the treatment of chronic pain." Scientists from the U.S. and Israel also contributed to the study.
The study was supported by the Krembil Foundation, the Louise and Alan Edwards Foundation, the US National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR) and SickKids Foundation.
About McGill University
Founded in Montreal, Que., in 1821, McGill is Canada's leading post-secondary institution. It has two campuses, 11 faculties, 11 professional schools, 300 programs of study and more than 36,000 students, including 8,300 graduate students. McGill attracts students from over 150 countries around the world, with more than 7,200 international students making up 20 per cent of the student body. Almost half of McGill students claim a first language other than English, including more than 6,200 francophones. For more information, please visit www.mcgill.ca
About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world's foremost paediatric health-care institutions and is Canada's leading centre dedicated to advancing children's health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada's most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit www.sickkids.ca.
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