WebMD Medical News
Daniel J. DeNoon
Louise Chang, MD
Sept. 29, 2008 -- Arthritis hurts, and that pain
itself may be what keeps the disease going, mouse studies suggest.
When a pain signal from an arthritic joint reaches the spine, there's a
burst of chemical signals, note University of Rochester researcher Stephanos
Kyrkanides, DDS, PhD, and colleagues.
One result of this burst of signals is that the spine becomes inflamed in
the area where the nerve from the joint attaches. Another result is that
signals travel backward from the spine to the joint.
If that signal is interrupted, Kyrkanides and colleagues find, two things
As might be expected, the joint is less painful. But to their surprise,
Kyrkanides found that interrupting this joint/spine "cross talk" allows
the joint to heal in mice with osteoarthritis.
"This cross talk is oil to the fire of arthritis," Kyrkanides tells
WebMD. "Trying to stop joint inflammation with the traditional drugs we
have is inadequate -- because it tries to address the joint but fails to
address this newly discovered mechanism where pain is progressing along the
nerve from the spine."
In studies with arthritic mice, the researchers used a gene therapy to block
a chemical messenger, IL-1B. The mice stopped their pain behavior. And their
joints got better.
"It proves the processing of pain in the joint actually contributes to
arthritis itself," Kyrkanides says. "We were very impressed to see we
could control arthritis progression and allow for spontaneous healing if, by
targeting IL-1B, we could control the pain at the spinal cord or along the
It's a "very exciting" finding, says osteoarthritis expert Farshid
Guilak, PhD, professor of orthopedic surgery at Duke University.
"This can open up a whole new way of treating osteoarthritis by saying
if you treat pain properly, you can affect the disease," Guilak tells
WebMD. "That is opposite of what we say now. We worry if you just treat the
pain, it can make the joint worse because the patient will overuse it. So if
pain affects joint degeneration, it would point to very exciting ways to
develop new treatments for arthritis."
The idea that pain can keep a disease going makes sense to pain expert Allan
Platt, PA-C, of the Emory University School of Medicine.
"This is evidence you can actually reduce disease severity by treating pain," Platt tells
WebMD. "It is an important discovery that changes in the joint happen
because of signals in the pain loop."
Although Kyrkanides and colleagues are working on a gene therapy that could
be used in humans, existing drugs already target relevant chemical signals
along the pain circuit. One is the IL-1 blocker Kineret, used by adults with
treatment-resistant rheumatoid arthritis. It is not
approved for treating osteoarthritis.
Because it dampens immune responses, it increases the risk of infections.
Kyrkanides suggests that such drugs might be most effective for
osteoarthritis if injected directly into the point where the nerves from
affected joints meet the spine.
"This would be quite feasible and one of the first things to try in a
pilot study," says Guilak. He notes that Kineret is already being tested in
patients with osteoarthritis -- but as a systemic or inside-the-joint
treatment, not as a way to block the pain circuit.
"The beauty of this is it does not require the invention of new drugs,
just new uses of existing medication," Kyrkanides says.
He predicts that in the future, the feedback-loop theory of osteoarthritis
will change the way doctors treat the disease.
"This is a radical shift in our understanding of osteoarthritis,"
Kyrkanides says. "The big change here is pain treatment at the right
targets has to be an integral part of the overall management of
The Kyrkanides paper appears in the October issue of the journal
Arthritis & Rheumatism.
SOURCES:Fiorentino, P.M. Arthritis & Rheumatism, October 2008; vol 58: pp
3100-3109.Stephanos Kyrkanides, DDS, PhD, associate professor, University of Rochester
Eastman Dental Center, N.Y.Allan Platt, PA-C, Emory Physician Assistant Program, Emory University
School of Medicine, Atlanta.Farshid Guilak, PhD, professor of surgery, orthopedic surgery, and
biomedical engineering, Duke University, Durham, N.C.
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