Summer 2005

Inflammation Suspect in Disc Pain

When Jeffrey Lotz, Ph.D., joined the lab 10 years ago, he envisioned that his work would evaluate the structure of the human spine using mechanical engineering tools similar to those used to examine man-made structures such as bridges.

Lotz, director of UCSF's Orthopaedic Bioengineering Laboratory, found that the spine's design, when analyzed from an engineering perspective, works pretty well for what it has had to do during most of human history -- support a human being's activities for most of his or her lifetime or about 40 years. But just as the parts of a bridge may wear out over time, parts of the spine also start to break down. Because humans are living longer than they used to, this can present a problem.

"Degeneration of the spine is commonly a biological adaptation to loading," says Lotz, who contends the spine isn't a problem for most people until middle age. "Our spines haven't adapted to us living past 40."

In collaboration with the Bioengineering department at UC Berkeley, Lotz and his colleagues have come to believe that the structure of the spine isn't the problem. It's what we do with our backs that triggers mechanical and chemical responses that produce pain.

The design starts to fail because of chemical changes in the vertebral discs, which are the largest organs in the body that are not perfused with blood. Instead, the discs exchange the products of respiration and metabolism through the ends of the adjacent vertebrae and via the muscle tissues that surround the spinal column. With age, the bone ends start to seal themselves and the discs endure diminished respiratory and metabolic exhange.

Although a healthy disc is good at cushioning the movement of the adjacent bones, it is not very good at responding to undue pressure or injury. Lotz said an injured disc can generate inflammatory products that result in pain. In other parts of the body, inflammatory chemicals trigger a cellular response that orchestrates healing. In the disc, with no blood vessels, the inflammatory agents have a hard time initiating healing and can be a principal factor in chronic pain.

"I think this is a fairly new perspective — that disc pain is the result of an aberrant healing response," Lotz says.

He admits that this perspective has resulted in a drastic change in his group's research.

"We've really had to evolve," he says. "I'm a mechanical engineer by training. But as an engineer, you need to be able to use the appropriate tools to solve your problem. So right now, our lab is 60 to 70 percent biology-oriented."

The 15 to 20 different research projects underway in his lab range from clinical design questions involved in evaluating different artificial discs to cell culture experiments examining the possibility of someday healing discs with new, cell-based therapies.

His lab is investigating whether total disc replacements can be successful in the long run or whether it's possible to just replace the dried-out nucleus or perhaps inject a new, tissue-engineered nucleus through the skin. Other questions under study include:

  • Could growth factors be used to stimulate disc healing?
  • Will it help back-pain patients to inject into the disc drugs that inhibit the production of inflammatory agents?
  • How can one inject medication into a disc without it being forced out by the high pressures produced in the disc through normal movement?
  • How can we quantify disc degeneration? At present, there is no objective marker of degeneration and it's not unusual for people with virtually identical discs to have very different levels of pain.
  • With minimally invasive surgeries diminishing the risks of surgical complications, would it make sense to do preventive spine operations before a problem occurs?

Answering these questions will involve the continued collaboration of the lab with the clinical members of the orthopaedic faculty. Lotz and his colleagues have already had a lot of experience with seeing their projects evolve into clinical therapies and they are looking forward to new challenges.

"There are still plenty of interesting problems to solve," Lotz says.

Jeffrey Lotz can be contacted at (415) 476-7881.

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