[MOL] A new aproach to cancer pain.....bone cancer info. [01207] Medicine On Line

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[MOL] A new aproach to cancer pain.....bone cancer info.

A New Approach to Cancer Pain
John Casey, Medical Writer


Researchers who work with cancer patients say the pain caused by the disease when it spreads to the bone is as indescribable as it is relentless. Although opiate-based painkillers offer some relief, they also can significantly impair mental function. And even opiates can fail to adequately decrease pain. The pain can become so extreme in some cases that amputation may be used as a means of providing relief.

But scientists from the Department of Veterans Affairs (VA) have developed a research model based on molecular changes in nerve cells over time that may lead to new treatments for severe pain in cancer patients, especially that of bone cancer. Results of their study appear in the December 15 issue of the Journal of Neuroscience.

Model for Pain Relief

"For the first time, we have a model to methodically determine what actually causes the pain and we can now begin to develop new therapies that avoid the undesirable side effects of those currently in use," reports team coleader Patrick W. Mantyh, PhD, JD, a research scientist at the Minneapolis VA Medical Center and neuroscientist at the University of Minnesota.

"For the first time, we have a model to methodically determine what actually causes the pain and we can now begin to develop new therapies that avoid the undesirable side effects of those currently in use."

"The uniqueness of this model arises out of a scientific collaboration between a basic scientist who studies pain," says Dr. Mantyh, "and an orthopedic surgeon, Dr. Denis Clohisy, whose primary patient population is individuals with severe cancer pain."

To create the model, researchers injected tumor cells into the thighbones of mice. "We specifically developed the model in the mouse because this will allow our group, other scientists, and the pharmaceutical industry to bring to bear on cancer pain the enormous advances in genetics that have been made in mice," says Mantyh.

Over time, the mice--like humans--guarded the affected limb as bone destruction increased and the sensory neurons (nerve cells) became hypersensitive. As the cancer progressed in the bone, Mantyh and his colleagues identified two specific types of pain associated with the disease.

Pain Types

Initially, the pain is dull and general, the type that usually leads human patients to seek a diagnosis. At this stage, very little bone destruction has taken place, but malignant cells in the bone appear to excrete compounds that cause the nerve cells to become especially sensitive.

These compounds eventually induce a reorganization of the spinal cord's neurochemistry, which scientists speculate may be part of the reason why bone cancer pain can be so intense and difficult to treat.

"What happens--we think--is that the tumor itself may be leading to changes in the sensory fibers that run throughout the bone," says Mantyh. "We think the tumor sensitizes those fibers. What leads to the very severe pain is--when the tumor is stimulating bone destruction, and the bone has become so eroded that normal movement induces a kind of microfracture--that the normal bone formation process can't keep up with."

As the bone destruction increases, a more intense pain develops. At this stage, the weakened bone often fractures and "breakthrough" pain (which "breaks through" the buffer provided by analgesic drugs) happens. The scientists speculate that the breakthrough pain is caused by mechanical distortion of the sensitized nerve fibers that run through the thin layer of cells that forms a sheath over the bone.

"The change in the spinal cord in the animal with this bone cancer pain is unlike inflammatory or neuropathic pain," says Mantyh. "We started thinking that cancer pain would be a subset of one of those two types of pain. But the reorganization that occurs in the spinal cord is something we've never seen before."

How Cancer in the Bone Starts

About 400,000 people suffered cancer-related bone pain in the United States in 1998. In most of these cases, the cancer had metastasized from soft tumors in the breast, ovaries, prostate, or lung to the bone. For reasons still unknown, the pain is particularly intense, and, because it quickly spreads through the skeletal structure, the cancer is very difficult to treat because of the high level of radiation required to attack it.

As the disease progresses, so does the intensity of the pain, until the only effective treatments are morphine-based drugs. However, the narcotic side effects of these drugs, including decreased cognitive ability and respiratory depression, significantly diminish the patient's quality of life. Ironically, advances in the treatment of cancer have succeeded in prolonging the lives of these patients, making the need for improved pain treatment even greater.

"As tumor therapy has improved, you now can slow it down, whereas it used to be very rapid, but the pain is still there," says Mantyh. "The usefulness of the mouse model is that it allows us to try new pain treatments to evaluate how effective they are. If we can find ways to restore the spinal cord to its normal neurochemistry, we may be able to get the quality of life back for the patients in pain. It's remarkable how much quality of life a cancer patient can regain when the pain is managed successfully."

What's Next

Currently, the research group led by Mantyh and Dr. Clohisy are using the model to identify the molecular mechanisms that generate bone cancer pain. Based on these insights, they are testing novel therapies that are more specific in their targets. The research team hopes these "specific target" drugs will eventually replace the "general target" narcotics currently in use.

Additionally, Mantyh and Clohisy believe that progress in understanding and treating bone cancer pain will provide insights into potential therapies for pains arising from other cancers.

2000 by Medscape Inc. All rights reserved.

John Casey is a staff member of CBSHealthWatch by Medscape.

Warmly, lillian

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