MIAMI _ Molecular neurosurgery, a new approach for treating
chronic pain, is showing considerable promise in early-stage
experiments with animals, pain specialists reported Wednesday.
The novel method involves delivery of a toxic compound directly
to those nerve cells that transmit pain messages up the spinal cord
to the brain.
Researchers outlined the latest results Wednesday at the Society
for Neuroscience's annual meeting in Miami. They said limited
trials in humans could begin in about two years.
If the therapy works, sufferers of hard-to-treat chronic pain,
as well as severe pain from cancer and other terminal conditions,
would get another alternative to standard neurosurgery or
pain-deadening drugs, both of which can be effective but also carry
risks and side effects.
The new technique offers permanent relief through a one-time
injection into the fluid-filled space surrounding the spinal cord.
Such injections could be given in a doctor's office, without need
for hospitalization or even follow-up shots.
The method takes advantage of a fast-growing body of knowledge
about the peculiar way pain signals travel through the nervous
system. In the case of chronic severe pain, such signals often are
carried through pathways paved by a neurotransmitter known as
substance P. Less severe and short-term acute pain signals _ which
are beneficial because they warn of injury _ move on a different
track.
Molecular triggers in the spinal cord, called receptors, sit on
the surface of neurons until they lock onto substance P. At that
point, the receptor and neurotransmitter move together inside the
neuron, switching it on and allowing the pain message to keep
moving.
Researchers came up with the idea of taking advantage of this
system as a way to mark the chronic-pain pathways for destruction,
while at the same time using the substance P receptors as a gateway
to get inside the target neurons.
So far, experts said, the substance P delivery ploy is working
about as well as they had hoped _ although nobody can predict what
the effect might be in people.
In standard neurosurgical procedures, pain pathways in
particular regions of the spinal cord are destroyed by cutting or
applying heat. But that can lead to loss of motor function or
sensation, and sometimes the spinal cord manages to rewire itself
to once again let the pain messages through.
Molecular neurosurgery could be much more precise, because
``you're letting the cells select themselves,'' said Patrick Mantyh
of the Veterans Administration Medical Center and the University of
Minnesota in Minneapolis.
Ronald Wiley, a neurologist at the Vanderbilt University and VA
Medical Center in Nashville, Tenn., has been collaborating with
Douglas Lappi of San Diego-based Advanced Targeting Systems to
develop a commercial treatment.
They presented new data at the neuroscience meeting showing that
a combination of substance P and a toxin called saporin had the
desired effect in tests on rats. Pain signals were reduced by more
than 90 percent, they reported, and the effect lasted for as long
as eight to nine months of follow-up observation.
They found no significant side effects once dosages were
adjusted properly, Wiley added. Further studies in primates are
just beginning. If those succeed, Advanced Targeting intends to
seek Food and Drug Administration approval to test it in humans.
``It's a very sophisticated technique,'' said Lorne Mendell,
pain expert at the State University of New York at Stony Brook, who
called it ``a particularly spectacular example'' of putting
fundamental neurochemistry and spinal anatomy to work on a serious
clinical problem.
He stopped short of predicting ultimate victory in the war on
pain, however. ``I'm just optimistic that we will get to the next
point'' in the development process, he said.
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(The San Francisco Chronicle Web site is at
http://www.sfgate.com )
