Bone Cancer Pain May Be Eased
By JANET McCONNAUGHEY
.c The Associated Press
NEW ORLEANS (AP) - The intense, debilitating pain of bone cancer can be
relieved by blocking the growth of cells which eat away at the bone,
scientists at the University of Minnesota say.
The cancer ``hijacks the bone into destroying itself,'' but a naturally
occurring protein, called osteoprotegerin, can stop that process, says
Patrick Mantyh, a neurosystems professor in the university's Department of
Preventive Sciences.
In mice, the protein appeared to stop bone destruction and relieve the pain
within two days, Mantyh said. Amgen Inc. began human safety tests with a few
patients in late 1999, but cannot say when they will be completed, spokesman
David Kaye said.
Mantyh was among thousands of scientists who recently presented their work to
the Society for Neuroscience. More than 400 studies were submitted on pain
alone.
More than 1.2 million people a year are diagnosed with cancer in the United
States. Hundreds of thousands will face agonizing pain.
Bone cancer causes two kinds of pain: a dull ache that grows over time and
intense pain brought on by movement. If it has spread to the spine, even
breathing hurts.
The vast majority of bone cancers have spread from the breast, prostate, lung
or colon or other areas into bones. Only 2 percent start in the bone, Mantyh
said.
Bone-destroying cells, called osteoclasts, usually work in balance with cells
which create bone. But something secreted by the tumor cells - scientists
don't know just what, but are working to find out - kicks the osteoclasts
into ``hyperdrive,'' Mantyh said.
``If a normal person would have, say, 10 osteoclasts, these patients have a
thousand. They're bigger and more active than you'd ever find in a normal
person,'' he said.
Osteoprotegerin does nothing to the tumor cells, but cancels their effect on
osteoclasts, he said.
Mantyh said the osteoclasts also seem to hypersensitize nerves which carry
pain stimuli to the brain. Even a gentle touch can cause excruciating pain.
In mice, that extreme sensitivity can be tested by stroking a foot with the
end of a very thin fishing line, or by shining a lamp on the floor of its
cage, to heat it slightly.
The osteoprotegerin studies are very exciting, said Dr. Richard Payne, chief
of pain and palliative care services at Memorial-Sloan Kettering Cancer
Center and a professor of neurology and pharmacology at Cornell Medical
College.
``This is the kind of data that will get oncologists and clinicians excited
about taking this work from the laboratory to the clinic as soon as
possible,'' said Payne, who was not connected with the studies.
Drugs often do little to relieve bone cancer pain and can cause problems such
as drowsiness, difficulty thinking and severe constipation.
One study looked at two of those drugs.
George Wilcox, also of the University of Minnesota, said studies in mice
suggest that clonidine and morphine work much better when taken together by
mouth than when injected into the spine, either alone or together.
If people have the same response as mice, he said, it might be possible to
give one-tenth the current dose of either if they were given together.
Payne said that might be worth studying.
Yet another study by Dr. Aaron Filler, a neurosurgeon at the University of
Cambridge in the United Kingdom and colleagues at the University of
California, Los Angeles, used the nerves themselves to deliver drugs. Nerve
cells carry messages from one cell to another by moving molecules along
fibers called axons, which can be anywhere from a fraction of an inch to 4
feet long.
The way they do this has been the topic of 20,000 to 30,000 papers over the
last few decades. But they haven't been used to deliver medicine before, said
Filler, who created a British company which holds rights to his delivery
system.
He and other researchers hooked up an ``axonal transport facilitator'' to a
long molecule, and then attached drug molecules to the long tail. The complex
of molecules can be injected under the skin or into muscle of an area which
hurts, and the nerves carry it where it is needed, Filler said.
Just what happens in the nerves after that is still being studied.
Filler said one injection of gabapentin - a drug used both as an
anti-convulsant and to alleviate pain arising from the nerves themselves -
reduced hypersensitivity by half for several days.
``Using one-thousand times less than the usual dose, a single injection gave
very significant pain relief for four days,'' he said.
It is an exciting approach, Payne said. ``Theoretically it is quite
attractive, and intuitively it's attractive.''
Claire Hulsebosch and her colleagues at the University of Texas Medical
Branch at Galveston looked at the hypersensitivity caused by spinal cord
injuries.
The study conducted by Hulsebosch, Mary Eaton of the Miami Project and
graduate student Bryan Hains used bioengineered cells which produce serotonin
to treat such pain, transplanting them into the injured area.
The cells were designed to multiply only at temperatures lower than a rat's
body temperature, so they could not create tumors.
The cells survived and secreted serotonin. The animals were less likely to
flinch when touched by thin fishing line or to lick their paws when the floor
of their cage was heated.
``And the rats walk better,'' she said.
On the Net:
University of Minnesota: http://www.umn.edu
The Society for Neuroscience: http://www.sfn.org
Memorial-Sloan Kettering Cancer Center: http://www.mskcc.org
AP-NY-11-19-00 1202EST
Copyright 2000 The Associated Press. The information contained in the AP news
report may not be published, broadcast, rewritten or otherwise distributed
without the prior written authority of The Associated Press. All active
hyperlinks have been inserted by AOL.
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