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.
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.
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."
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."
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.
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John Casey is a staff member of CBSHealthWatch by Medscape.