Customizing relief

By Mark Witten

One in five Canadians suffers from chronic pain. Not every patient responds to medication in the same way – and some people don’t respond at all. Renowned pain genetics researcher Luda Diatchenko is working on personalizing treatment for each sufferer.

Imagine pressing your hand on a stove burner and turning it on. How long would it take you to feel pain? Depends on your genes, says Dr. Luda Diatchenko, a professor in the Faculty of Medicine’s Department of Anesthesia and in the Faculty of Dentistry. “Half of our pain sensitivity is determined by our genetic makeup,” explains the scientist, who joined McGill and its Alan Edwards Centre for Research on Pain in 2013 as Canada Excellence Research Chair (CERC) in human pain genetics.

A decade ago, Diatchenko performed similar pain-sensitivity tests on 202 healthy female volunteers at the University of North Carolina (UNC). In this pivotal experiment, researchers pressed a small metal cylinder against the skin of the volunteers, heating it mildly to determine the tolerance level of the subject and then delivering pulses of heat at a slightly lower temperature. The results led Diatchenko to uncover a key genetic clue to help solve the perplexing puzzle of why some people are able to withstand high levels of discomfort while comparable pain causes others to suffer intensely. She discovered that the women who felt the heat more quickly and experienced more pain with each additional pulse of heat carried a variant of a gene called COMT, which produces an enzyme that controls the level of stress hormones by metabolizing them.

This high-pain sensitivity (HPS) variant amplifies pain because it produces less of the COMT enzyme, leading to an excess of non-metabolized stress hormones. Carriers of the HPS variant are also more likely to develop chronic pain conditions, such as fibromyalgia (characterized by widespread musculoskeletal aches and stiffness) and temporomandibular joint disorder (a facial muscle pain condition), which affect about 10 per cent of Canadians. “This finding was exciting because it was the first time a researcher showed an association between a common genetic marker and substantially different experiences of pain,” says Diatchenko.

Building on these findings, Diatchenko’s goal today is to map out other genetic mechanisms at the roots of chronic pain to help develop much more effective personalized pain therapy strategies for common conditions like lower back pain, tension headaches and arthritis. “Pain is the number one reason why people see doctors, and the economic costs to society are greater than the costs of cancer, diabetes and heart disease combined,” she says. “Clinicians want to know what medication will be best for each patient and we want to give them the tools to tailor treatment to the patient’s genetic profile.”

One avenue Diatchenko is exploring is the treatment of pain using drugs that block beta receptors (proteins that bind to stress hormones, thereby weakening their effects), a class of drugs commonly used to manage heart disease. In a 2010 study, Diatchenko showed that chronic pain patients carrying the HPS variant of the COMT gene got more pain relief from the beta blocker propranolol than those with other variants of the gene. Now, she plans to test the effectiveness of another beta blocker for the carriers of the HPS variant. “This beta blocker targets the pain receptors better, so it reduces pain more efficiently and has fewer side effects. [Propranolol’s side effects include drowsiness and depression.] At a later stage, if we find it’s not effective enough, we could also modify the drug specifically for the treatment of pain,” she says.

Diatchenko, who holds a medical degree and a PhD in molecular biology from the Russian State Medical University, started her career in the biotech industry in California, developing new and still widely used tools for analyzing gene expression and regulation. In 2000, she joined a pain research group at the University of North Carolina. “I found the field of chronic pain research so fascinating and so neglected from a medical research point of view, given the complexity of the problem. I thought it showed a lot of promise in terms of what could and needed to be done,” says Diatchenko.

In 2005, she also co-founded Algynomics, a pain genomics company that is helping to move some of her promising discoveries toward clinical applications faster. For example, the results of her UNC pain-sensitivity study led to the development of a test for the HPS variant of the COMT gene that is used by biotechnology companies that use genetic markers. “Coming from an industry background, I saw Algynomics as providing me with the opportunity to oversee the transformation process from discovery to application. Also, by collaborating with pharmaceutical companies, it gives our research group access to large additional cohorts of chronic-pain patients,” says Diatchenko, who continues to be involved with Algynomics.

The CERC program, established by the Canadian government in 2008, provides Diatchenko’s research team at McGill with $10 million in federal funding over seven years and more than $20 million in matching funds from private and public partners. This funding will allow the University to recruit five new professors to support Diatchenko’s research. “Personalized medicine to treat chronic pain is a new, cutting-edge area that we wanted to develop,” says Fernando Cervero, director of the Alan Edwards Centre for Research on Pain. “We have excellent people doing brain imaging, preclinical studies in pain genetics and epigenetics, and a very strong clinical research group. Luda’s expertise will help build on our worldwide reputation as a pain research centre so that McGill can be a leader in developing personalized pain medicine over the next 15 years.”

Luda Diatchenko holds the Canada Excellence Research Chair in Human Pain Genetics. The $10-million CERC funding from the government of Canada is matched by more than $20 million from private and public sources, including the government of Quebec, the Canada Foundation for Innovation, Pfizer Canada and McGill University. The Alan Edwards Centre for Research on Pain is supported by the Louise and Alan Edwards Foundation.