Study Suggests New Way to Treat Chronic Pain

Gene that encodes crucial pain receptor may be key to therapy for major health problem

TORONTO, ON–(ENEWSPF)–March 26, 2012.  A University of Toronto scientist has helped identify a major gene affecting chronic pain sensitivity, an often debilitating problem that impacts nearly one in five people.

While there have been many breakthroughs in understanding the basic biology of pain over the past two decades, a major scientific challenge has been understanding why certain people develop pain and why others – including those with similar disorders or injuries – do not. Another challenge has been developing individualized therapies for specific patient populations.

Now, research published online in Nature Medicine points to solutions to both challenges. A research team led by U of T Professor Michael Salter of The Hospital for Sick Children (SickKids) and Professor Jeffrey Mogil of McGill University in Montreal has identified a major gene affecting chronic pain sensitivity. The findings also suggest a new approach to individualizing treatment of chronic pain.

The gene identified by the researchers encodes the pain receptor known as P2X7. Specifically, they 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. The researchers found that pain behaviours were dramatically reduced by using a peptide that targets pore formation.

The team examined genetic differences in human patients suffering from chronic post-mastectomy pain and osteoarthritis. In both cases, they found 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 Mogil, E.P. Taylor Professor of Pain Research in McGill’s Department of Psychology.

Salter, a Professor in U of T’s Department of Physiology who holds the Canada Research Chair in Neuroplasticity and Pain, 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.