Pain Causes Arthritis

LiveScience Staff

LiveScience.comTue Sep 30, 1:55 PM ET

As we all know, arthritis, the leading cause of disability among people over 55,
causes pain. But new research suggests that pain also causes arthritis.

Pain should no longer be thought of just as a symptom of arthritis, according to
the study in the October issue of the journal Arthritis and Rheumatism. Pain
signals originating in arthritic joints, and the biochemical processing of those
signals as they reach the spinal cord, worsen and expand arthritis, the
researchers say.

In addition, the researchers found that nerve pathways carrying pain signals
transfer inflammation from arthritic joints to the spine and back again, causing
disease at both ends.

Technically, pain is a patient's conscious realization of discomfort. Before
that can happen, however, information must be carried along nerve cell pathways
from, say, an injured knee to the pain processing centers in dorsal horns of the
spinal cord, a process called nociception. The current study provides strong
evidence that two-way, nociceptive "crosstalk" may first enable joint arthritis
to transmit inflammation into the spinal cord and brain, and then to spread
through the central nervous system (CNS) from one joint to another.

Furthermore, if joint arthritis can cause neuro-inflammation, it could have a
role in conditions like Alzheimer's disease, dementia and multiple sclerosis.

Armed with the results, researchers have identified likely drug targets that
could interfere with key inflammatory receptors on sensory nerve cells as a new
way to treat osteoarthritis (OA), which destroys joint cartilage.

The most common form of arthritis, osteoarthritis eventually brings deformity
and severe pain as patients loose the protective cushion between bones in
weight-bearing joints like knees and hips. About 27 million Americans have
osteoarthritis and 1.3 million have rheumatoid arthritis, according to the
Arthritis Foundation.

"Until relatively recently, osteoarthritis was believed to be due solely to wear
and tear, and inevitable part of aging," said Stephanos Kyrkanides, associate
professor of Dentistry at the University of Rochester Medical Center.

"Recent studies have revealed, however, that specific biochemical changes
contribute to the disease, changes that might be reversed by precision-designed
drugs," he said. "Our study provides the first solid proof that some of those
changes are related to pain processing, and suggests the mechanisms behind the
effect," said Kyrkanides, whose work on genetics in dentistry led to broader
applications.

The common ground between arthritis and dentistry: The jaw joint is a common
site of arthritic pain.

How the pain signal works

Past studies have shown that specific nerve pathways along which pain signals
travel repeatedly become more sensitive to pain signals with each use. This may
be a part of ancient survival skill (if that hurt once, don't do it again).
Secondly, pain has long been associated with inflammation (swelling and fever).

In fact, past research has shown that the same chemicals that cause inflammation
also cause the sensation of pain and hyper-sensitivity to pain if injected.
Kyrkanides' work centers around one such pro-inflammatory, signaling chemical
called Interleukin 1-beta (IL-1beta), which helps to ramp up the body's attack
on an infection.

Specifically, Kyrkanides' team genetically engineered a mouse where they could
turn up on command the production of IL-1beta in the jaw joint, a common site of
arthritis.

Experiments showed for the first time that turning up IL-1beta in a peripheral
joint caused higher levels of IL-1beta to be produced in the dorsal horns of the
spinal cord as well.

Crosstalking signals

Using a second, even more elaborately engineered mouse model, the team also
demonstrated for the first time that creating higher levels of IL-1beta in cells
called astrocytes in the spinal cord caused more osteoarthritic symptoms in
joints.

Past studies had shown astrocytes, non-nerve cells (glia) in the central nervous
system that provide support for the spinal cord and brain, also serve as the
immune cells of CNS organs. Among other things, they release chemicals like
IL-1beta to fight disease when triggered. The same chemicals released from CNS
glia may also be released from neurons in joints, possibly explaining how
crosstalk carries pain, inflammation and hyper-sensitivity back and forth.

In both mouse models, experimental techniques that shut down IL-1beta signaling
reversed the crosstalk effects. Specifically, researchers used a molecule,
IL-1RA, known to inhibit the ability of IL-1beta to link up with its receptors
on nerve cells.

Existing drugs (e.g. anakinra, which is indicated for rheumatoid arthritis) act
like IL-1RA to block the ability IL-1beta to send a pain signal through its
specific nerve cell receptor, Kyrkanides said, and his group is exploring a new
use for the drugs as an osteoarthritis treatment.

The crosstalk compounds

The implications of this process go further, however, because the cells
surrounding sensory nerve cell pathways too can be affected by crosstalk. If 10
astrocytes secrete IL-1beta in response to a pain impulse, Kyrkanides said,
perhaps 1,000 adjacent cells will be affected, greatly expanding the field of
inflammation.

Spinal cord astrocytes are surrounded by sensory nerve cells that connect to
other areas of the periphery, further expanding the effect. According to
Kyrkanides' model, increased inflammation in the central nervous system can then
send signals back down the nerve pathways to the joints, causing the release of
inflammatory factors there.

Kyrkanides' colleagues for this research included M. Kerry O'Banion, Ross
Tallents, J. Edward Puzas, Sabine M. Brouxhon, Paolo Fiorentino, all at the
University of Rochester School of Medicine and Dentistry. This work was
supported in part by grants from the National Institutes of Health.

"Our study results confirm that joints can export inflammation in the form of
higher IL-1beta along sensory nerve pathways to the spinal cord, and that higher
IL-1beta inflammation in the spinal cord is sufficient in itself to create
osteoarthritis in peripheral joints," Kyrkanides said. "We believe this to be a
vitally important process contributing to orthopaedic and neurological diseases
in which inflammation is a factor.

Seth-Deborah Roth CRNA,CCHt,CI
www.hypnotherapyforhealth.com
read my blog at www.hypnotichealth.blogspot.com