TORONTO - The author C.S. Lewis once observed that pain is God's megaphone. But for a handful of individuals around the world with an extremely rare genetic condition, pain is the sound of silence or, at most, a faint whisper.
A Canadian-led international research team has identified 17 people from seven countries born with a mutated gene that has rendered them either unable to feel pain or to experience it at levels far below normal.
And the scientists hope the knowledge they have gleaned from these individuals' unique genetic makeup will one day lead to drugs that mimic the effects of the mutation to help millions of people worldwide suffering from uncontrolled chronic pain.
"Pain is a very important defence mechanism for all humans and this disorder called congenital insensitivity to pain (CIP) is actually a very rare human genetic disease," said Dr. Simon Pimstone, President and CEO of Xenon Pharmaceuticals Inc., one of the investigators involved in the research.
"We have pinpointed the gene that could be responsible for cases of patients who have an inability or reduced ability to feel pain."
The scientists worked with members of nine families in isolated parts of Canada (Newfoundland), Argentina, France, the United States, Switzerland, Italy and England. DNA testing showed that each had mutations on the same gene, called SCN9A, on chromosome 2.
When mutated, the SCN9A gene does not express a specific protein that allows pain to be felt. It mucks up the signals between nerve cells at the site of an injury -- say from a burn or cut -- and the neurons in the brain responsible for recognizing pain.
"It's just like electricity moving on an electricity line," Pimstone said from Vancouver. "We send the particular signals from cell to cell in our nervous system."
While feeling little or no pain may seem like a godsend (think painless childbirth, for instance), in day-to-day life it can have devastating repercussions.
An affected child placing a hand on a hot stove would discern heat, but would not feel the scorching pain that would make most of us yank our hand away at lightning speed.
People born with the genetic mutation have reported scalding themselves with boiling water, burning their mouths on red-hot food and drinks; biting their tongues until they bleed; bruising and cutting themselves from head to toe; and even breaking bones -- all unaware of the damage their bodies have sustained.
"Trauma is a very helpful preventive action, you do something if you've got pain and you do it early," said senior researcher Dr. Michael Hayden, a geneticist from the University of British Columbia and a co-founder of Xenon. "If you've got appendicitis, if you've got a pain in your tummy, you go to your doctor."
Being unaware of pain can mean delaying treatment -- and that can prove disastrous, Hayden said.
One affected individual from a French family unknowingly broke a leg and kept on walking around. Severe infection set in and the person "eventually lost their limb," he said.
Hayden said his role in the research, to be published online next week in the journal Clinical Genetics, was conceptual: looking for genetic abnormalities that can be turned on their heads to produce therapies for the widespread benefit of patients.
In this case, finding families with CIP has provided one of several target genes that the investigators hope will lead to drugs to treat people with chronic pain.
Xenon, a biotech company formed as an offshoot of UBC, "has made a few genetic discoveries that could potentially lead to the development of novel drugs for the treatment of pain," said Pimstone. But he expects it could be 10 years before such medications could be developed, tested and brought to market.
The researchers aren't the only scientists to pinpoint the genetic root of CIP. In December, a U.K.-led group reported on six members from three Pakistani families with mutations in the SCN9A gene.
That paper described a 10-year-old boy who performed "street theatre" by poking knives into his arms and walking on burning coals, never experiencing any pain. He died a few years later after jumping off the roof of a house.
The Canadian-led team, which identified the gene mutation about a year earlier, wanted to carefully confirm their findings in different ethnic groups before publishing their results.
"We wanted to make sure we had validated the discovery in different families," said Pimstone. "So not only is it from ... families from Pakistan, but we've now confirmed different mutations in the same gene in families from probably five or six other ancestries (family lines)."
Dr. James Henry, scientific director of the Michael G. DeGroote Institute for Pain Research and Care at McMaster University, said the findings from both the Canadian-led and U.K.-led research are "very enlightening."
While "cautiously optimistic" about the findings, Henry said "we're still very much at a primitive stage in understanding and harnessing this kind of knowledge."
But it is knowledge that is desperately needed, he said, noting that chronic, non-cancer pain affects one in five Canadians, many of whom get inadequate or zero relief from current drugs used to treat their conditions.
Those conditions include chronic pain from car accidents, diabetic and other forms of neuropathy, arthritis and the most common type of unremitting discomfort, low back pain.
"And these people are so debilitated we don't know about them," Henry said from Hamilton. "They don't go out. They can't go out... It's a silent epidemic."
The fallout from chronic low back pain alone costs the Canadian economy an estimated $8 billion a year, he said. "That's a huge amount, but it's also atrocious. It means that we're not reaching out adequately to such a huge number of people."
Unfortunately for the individuals affected by the mutated gene, the work they have "so generously" contributed to is unlikely to provide them with any benefit, said Hayden.
"It's their gift to the world in a way," he said. "It's a gift because delineating this provides opportunities for such important pain relief for the rest of the world."
"But it's a gift in the highest sense of the word, because it may not help them."
