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Ed Note: The following is
a press release from the University of Florida
March 2, 2004
GAINESVILLE, Fla. --- A potent neurotoxin can be used to zap rogue nerve
cells responsible for triggering chronic pain after paralyzing spinal cord
injury in rats, an approach scientists have labeled molecular neurosurgery,
University of Florida researchers report in the online edition of
Neuroscience Letters.
The neurotoxin acts on specific sites in the spinal cord, where it is
incorporated into nerve cells, which then die. By eliminating these cells,
researchers were able to significantly lengthen the time between injury and
any signs of pain behavior as well as decrease the severity of pain.
The research is part of ongoing efforts to explore the mechanisms of pain
after spinal cord injury. Surprisingly, up to 80 percent of people who
suffer from spinal injury develop some form of excruciating chronic pain at
or below the level of their paralysis, experts say. Many describe their
discomfort as burning, stabbing or even electric.
“Most people think spinal cord injury results in a loss of sensations below
the level of injury, but it turns out that spontaneous pain following spinal
injury usually is referred to parts of the body below the level of injury,
where there is no motor or sensory function,” said Robert P. Yezierski,
director of UF’s Comprehensive Center for Pain Research. “Pain following
spinal injury is a devastating consequence of injury. Many people would
gladly exchange relief of pain with a lot of other potential cures,
including the ability to walk.
“The unfortunate thing is we have no long-term effective treatments for this
type of pain,” added Yezierski, who also is associated with UF’s McKnight
Brain Institute and the College of Dentistry. “This is why we are trying to
develop novel approaches. We think that molecular neurosurgery could
potentially be an answer for this condition.”
The anatomy, the way cells function and the chemical language the spinal
cord uses to fire messages to the brain all change after an injury. In a
way, chronic pain after spinal cord injury is similar to phantom pain
experienced by some patients after amputation, and scientists think the
underlying mechanisms of these disorders may be similar.
“The rules that apply in the normal condition no longer apply in the injured
state,” Yezierski said. “So we’re dealing with a totally different
functional, structural and chemical entity following injury, and that’s been
the biggest challenge - to figure out what those changes are in the injured
spinal cord.”
UF researchers identified a population of nerve cells in the spinal cord
essential to relaying messages to the brain responsible for the referred
pain sensation many patients describe after spinal cord injury. The nerve
cells are located in a region associated with pain processing, and each has
a receptor on its surface that binds to a powerful pain transmitter known as
substance P.
As part of the study, funded by a $1.2 million grant from the National
Institutes of Health, scientists used a neurotoxin hooked to a compound that
docks at receptors on the surface of nerve cells in the spinal cord.
They injected the neurotoxin into the area surrounding spinal cord injury in
more than 60 rats, either at the time of injury or later, after the animals
began exhibiting a grooming behavior associated with pain. After the
neurotoxin was administered, researchers noted delays in the expected onset
and severity of pain-associated excessive grooming behavior. Higher doses of
the neurotoxin produced the most significant pain-relieving effect, although
a significant response also was seen at a lower dose.
Researchers believe that once the protein complex containing the neurotoxin
docks at the site, the cell allows it to enter. Inside the cell, the protein
and the neurotoxin separate. The neurotoxin then initiates chemical changes
that kill the cell.
“The results of the intervention have shown that this unique population of
neurons definitely contribute to the onset and maintenance of the
injury-induced pain behavior,” Yezierski said. “There’s reason to be
optimistic that we now are identifying therapeutic targets and strategies of
intervention that will hopefully lead to more effective therapies for the
treatment of this condition. We hope the approach that was used to identify
these neurons can be used clinically in individuals who have spinal cord
injury pain. Efforts are now under way to develop a clinical trial for this
particular approach.”
Similar studies conducted elsewhere have used the same molecular
neurosurgery approach to successfully treat other types of pain originating
from peripheral nerve damage or from inflammation. The UF study was the
first to try the technique to treat pain of a central origin.
“Spinal cord injury is an extraordinarily complicated set of events that
leads frequently to severe pain states that often are very difficult to
manage,” said Tony Yaksh, a professor and vice chairman for research in
anesthesiology at the University of California, San Diego.
“Dr. Yezierski’s paper looking at the effects of spinal delivery of this
toxin promises a novel approach to an otherwise very difficult-to-manage
disorder,” Yaksh said. “Of course, there’s a lot of work that remains to be
done, but in one fell swoop it provides significant insight into the
mechanisms of this disorder, that is to say, targeting this specific site
for the toxin to act in the spinal cord, and it provides the possibility of
a therapeutic intervention. We ourselves are involved in studying the safety
of substance P-saporin in other animal models, and there is a good
likelihood that this new peptide may in fact find its way into humans for
therapeutic treatment of a variety of complicated pain states. Dr.
Yezierski’s study seems to point directly to the importance of this
mechanism in pain secondary to spinal cord injury.”
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For more information contact:
Melanie Fridl Ross, 352-690-7051, ufcardiac@aol.com
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