WINSTON-SALEM, N.C. - Better management of persistent nerve-injury pain through a better understanding of how pain medicines operate is the goal of a new $6.1 million research center at Wake Forest University Baptist Medical Center. The Center for the Study of Pharmacologic Plasticity in the Presence of Pain is funded by a grant from the National Institute for Neurologic Diseases and Stroke of the National Institutes of Health.
For the next five years the center will investigate changes in the nervous system, particularly the spinal cord, in the presence of certain medicines and how those changes affect the sensation of pain. The research will take place both in the laboratory and in the clinic.
The research will focus on pain that persists from nerve injury in tissues that have since healed. Nerve-injury, or neuropathic, pain can be a burning or shooting feeling, often accompanied by painful feelings from otherwise normal events, such as light touch on the skin. Scientists believe that nerve activity in the spinal cord has a major influence over the perception of pain from damaged nerve endings.
James C. Eisenach, M.D., professor of anesthesiology and the principal investigator in the new pain center, used the example of sunburn. "Most people will recover from nerve injuries, just like their skin sensation returns to normal after a sunburn goes away. But a lot of people develop chronic pain, and when that happens there are changes in the spinal cord, with the chemicals and receptors. So even without the sunburn actually there, light touch can give them the sensation of pain."
As part of the center, Eisenach will lead a research project to study the pain-relieving mechanism of a blood-pressure medicine called clonidine. Although clonidine does not work for well for acute, trauma-induced pain, it is effective for pain following nerve injury - and at a much lower doses. Eisenach said he will test the theory that clonidine "stimulates a different circuit in the central nervous system that appears to be more important after nerve injury than before."
Another laboratory project will focus on changes in the nervous system that produce increased tolerance to narcotics such as morphine commonly used to treat pain. The research will study whether adding other medicines can stop or reverse those changes.
A third project will attempt to determine why certain pain-relieving drugs are much more potent in women than in men. Those drugs act on cells in the spinal cord called cholinergic cells, the same kinds of cells affected by nicotine. One of these types of drugs, called metanicotine, is patented by Eisenach and Wake Forest University School of Medicine and is made in Winston-Salem by Targacept Inc.
Animals, like humans, will abuse narcotics such as heroin, but rats that have experienced nerve injury that results in sensitivity to light touch have a much lower potential to abuse heroin that they are self-administering for their pain. A fourth laboratory project will study that phenomenon and try to determine what parts of the brain are being affected by heroin in the presence or absence of pain.
"The whole purpose of the grant is to better understand how to treat people," Eisenach said. Information gained from the laboratory projects will be applied to human patients in clinical trials through the Piedmont Pain Control Center, directed by Richard L. Rauck, M.D., clinical associate professor of anesthesiology.
Rauck said the center will concentrate on patients with a variety of pain, including lingering pain from back surgeries, industrial injuries that damaged a nerve, diabetic neuropathies, shingles pain, and possibly some residual cancer-related pain in people who are now disease-free.
He said the research will generate new information about - and hopefully more effective pain-relieving uses for - existing, FDA-approved medicines. "We''ll be looking at combinations of different drugs - how they work and how they work together in different types of these nerve pain states."
Eisenach and Rauck are also organizing a consortium of more than 100 doctors who treat chronic pain patients in a three-state area. The research center will also sponsor a symposium on pain each year for the Medical Center and the community, featuring nationally or internationally recognized experts in the basic science of pain research and the treatment of chronic pain conditions. The first symposium is planned for June 2002.
In addition to Eisenach and Rauck, principal investigators in the research center are Steven R. Childers, Ph.D., professor of physiology and pharmacology, Joseph R. Tobin, M.D., associate professor of anesthesiology and of pediatrics, and Thomas J. Martin, Ph.D., assistant professor of physiology and pharmacology.
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Contact: Mark Wright, (336) 716-3382; Bob Conn (336) 716-4977