Spinal intrigue

Spinal intrigue

A Calgary researcher tackles the mystery behind chronic back pain
May 6, 2009
Some cell structures in the disc are unusual.

Some cell structures in the disc are unusual. Here, large vacuole 'bubbles' inside cells are surrounded by a multi-layered membrane.
Dr. Christopher Hunter

Early in his university studies as a mechanical engineer, Christopher Hunter thought he wanted to be an aerospace engineer. But after working part-time for five years as an emergency medical responder, he discovered he was more interested in using his engineering expertise to address medical, rather than industrial, challenges. As he advanced through his PhD and then post-doctoral work in the rapidly emerging field of bioengineering, he decided to focus his research efforts on an enduring medical mystery: how and why human spinal discs break down and cause severe back pain.

“Disc-related back pain is a common and debilitating disorder,” says Hunter, an associate professor of mechanical engineering at the University of Calgary and a member of the university’s Centre for Bioengineering Research and Education. “But there’s still a lot we don’t know about why discs fail and what we can do to treat patients who are suffering.”

Hunter is currently one of only a handful of researchers worldwide investigating the role of specialized cells known as notochordal cells, which help build spinal discs in the human embryo. He is also conducting leading-edge research into how new tissue-engineering technologies might be used to grow a living disc in the lab that could then be used to replace a failing one.

Disc-related back pain affects an estimated 50,000 Canadians. Because such pain has a severe impact on a person’s mobility and quality of life, it results in more than 30 million restricted-activity days and costs the economy between $5 billion and $10 billion annually. While arthritis is about 10 times more common than back pain, Hunter notes that it costs the economy about one-tenth as much. “The fact is that if you’ve got a bum knee, you can probably still manage to get to work,” he says. “If you’ve got a bad back, that’s likely it for the day.”

Discs, the flexible parts of the spine between the vertebrae, are made up of a gelatinous core surrounded by flexible fibrous tissue. They cushion the bones and provide a degree of shock absorption. The exact causes of disc degeneration remain unknown. “A growing body of evidence suggests a strong genetic factor,” says Hunter. “Some of us are just predisposed.” There is also evidence that mechanical aspects, such as overload and chronic overuse and even smoking and obesity, could also be risk factors. “But could I point at somebody and say, ‘You have a certain risk of getting disc degeneration’? Absolutely not.”

Another enduring mystery is the pain that may or may not accompany disc degeneration. Disc failure does not always cause pain, and back pain is not always caused by disc failure. “You can look at the MRI of some individuals where a disc looks terrible, but they have no pain,” says Hunter. “And sometimes you can MRI people whose discs look fine, and they are screaming in agony. So we don’t even know where that pain is coming from.”

Dr. Christopher Hunter and his team have found

Dr. Christopher Hunter and his team have found some proteins are expressed and used in different ways in the disc.
Dr. Christopher Hunter

People with mild to moderate disc-related back pain can be treated with physiotherapy, massage or chiropractic procedures, but advanced degeneration commonly requires surgery — typically, by using a bone graft or instrumentation to fuse the affected vertebrae. Unfortunately, more than one-third of surgical fusions fail to yield positive results, and to add insult to injury, discs adjacent to the repaired area often break down following surgery.

Hunter is looking for potential ways to slow disc degeneration in its early stages, improve surgical outcomes and provide possible alternatives to surgical fusion.

In his lab, Hunter examines animal notochordal cells and, on occasion, human cells that become available after a child has undergone corrective spinal surgery. In humans, notochordal cells are lost and replaced by other cells by about age 10. But in certain animals, including cats, rabbits, pigs, rats and mice, notochordal cells remain intact for life. Dog cells can be the most instructive. In some breeds, the cells disappear over time; in others, they do not. The breeds that keep their notochordal cells experience much less back pain.

Hunter grows the cells in standard cell cultures to see what they secrete, what genes they express and how they respond to environmental stimuli. The research isn’t aimed at preventing the disappearance of notochordal cells. After all, says Hunter, there are likely good reasons for the loss, and “we don’t want to muck around with our natural history too much.”

“It’s more about understanding the language these cells are speaking and the signals they send that help build the original discs,” he says. “If we can then speak the same language to whatever cells we end up implanting, we might send them down the right pathways.

“The overlap between the two areas of research — regeneration and replacement — is that we’re trying to use the notochordal cells again. If they know how to instruct something to build a disc in the embryo, maybe they know how to instruct something to build a disc in the lab.”

Polarizing light microscopy of the annulus

Polarizing light microscopy of the annulus fibrosus, the tough outer layer of a spinal disc. The earliest signs of degeneration can only be detected by removing the tissue, which is not feasible in patients.
Dr. Christopher Hunter

The fundamental technology is in place for both cell implantation and disc replacement, but it will probably take many years to develop successful clinical procedures. “On the other hand,” says Hunter, “someone may come up with a key discovery tomorrow. That’s one of the fun things about science — you never know.”

In the meantime, physicians who treat disc-related back pain on a daily basis are anxious to see Hunter’s research results. “Back pain is certainly one of the biggest problems in modern society,” says Paul Salo, a Calgary-based orthopaedic surgeon. “So if there were an effective treatment or prevention, it would be a tremendous boon.”

Salo credits Hunter with taking what he calls “an inclusive approach, starting with potential causes and working through potential solutions, including tissue engineering.”

All the same, there are those nagging mysteries.

“There are still a lot of unknowns about back pain,” says Salo. “So to say this research is the key to resolving them would be premature. But it’s got a lot of promise.”