The individuality of pain

Discovery
by Mark Witten
Luda1

Luda Diatchenko is McGill’s new Canada Excellence Research Chair in Human Pain Genetics (Photo: Claudio Calligaris)

Why does one person with minimal tissue damage from arthritis suffer debilitating chronic pain, while another with major damage reports very little? The question is a riddle that Luda Diatchenko, McGill’s new Canada Excellence Research Chair (CERC) in Human Pain Genetics, is aiming to solve by pinpointing crucial genetic differences in people’s susceptibility to developing chronic pain conditions.

One in five Canadians suffers from chronic pain, but the root causes remain a perplexing puzzle for science and current treatments fail to give most patients effective pain relief. “Pain is the number one reason people consult doctors. But there’s no drug we can give that makes chronic pain go away. On a scale of zero to 10, existing treatments reduce the pain by only two to three units and a lot of people don’t respond at all,” says Diatchenko, a world leader in pain genetics who was formerly at the University of North Carolina. She joined McGill’s Alan Edwards Centre for Research on Pain in September.

Gene studies reveal that about half of our sensitivity to pain is determined by our genetic makeup. Diatchenko’s goal is to personalize pain diagnosis and treatment by unlocking the secrets of how specific variations in genes affect an individual’s pain perception and sensitivity. The right medications could then be developed and prescribed to more precisely fit the genetic and molecular pain profile of patients.

“If there were five drugs available to treat a particular condition, blood tests with genetic or other molecular markers would predict and help choose which drug will benefit the patient,” says Diatchenko, the recipient of McGill’s first CERC. Her research program will receive $10 million in federal funding and over $20 million in matching funds from private and public partners.

In 2005, Diatchenko uncovered a critical piece of the pain puzzle when she discovered that some people carry a specific variant of a gene, called COMT, which amplifies pain sensitivity. She further found that there were three commonly occurring variants of the COMT gene, resulting in low, average and high pain sensitivity. Those with the high pain sensitivity variant (HPS) were also more likely to develop chronic pain conditions, such as fibromyalgia and temporomandibular joint disorders, which affect about 10 per cent of Canadians.

Later, in a highly cited paper in Science, Diatchenko explained how the ultra-sensitive gene amplifies pain and can trigger a domino effect in chronic pain disorders. Diatchenko found that individuals with the HPS gene variant make smaller amounts of the COMT enzyme, which is crucial for regulating pain processing and signalling because it controls the release of stress hormones — dopamine, norepinephrine and epinephrine (adrenalin). Her study also suggested new possibilities for treating this patient subgroup, using drugs that would selectively target Beta 2 and Beta 3 receptors (proteins that bind to stress hormones like adrenalin).

Diatchenko is now working on developing new personalized treatments that will help chronic pain sufferers who carry the high-pain-sensitivity COMT gene by targeting the underlying pain mechanisms.

She will also team up with other McGill pain specialists to investigate other genetic differences that heighten pain sensitivity and which may contribute to chronic pain disorders — such as low back pain, tension headaches and arthritis — using her COMT studies as a model for translating basic discoveries into personalized treatments. “Our current drugs are extremely inefficient in treating chronic pain. People live with this for years and my goal is to reduce their chronic pain and suffering,” she says.

 

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