Scientists at the School of Medicine in the Program in Neuroscience  have discovered a key mechansim in the brain related to a devastating pain condition affecting patients suffering from spinal cord injury, multiple sclerosis and stroke. The condition, called Central Pain Syndrome, causes chronic pain that patients compare to being stabbed with a thousand burning knives. The pain is so severe and untreatable that suicide is a leading cause of mortality among those it afflicts. A team of researchers has traced the syndrome to a malfunction in the zona incerta, or "zone of uncertainty," an area of the brain about which little was known until now. The paper was published in the online version of the Journal of Neurophysiology.

 

"We hope that by understanding this underlying mechanism of Central Pain Syndrome, we can begin to think about potential treatments or preventive techniques," said the study's lead author Asaf Keller, PhD, professor, Department of Anatomy & Neurobiology.

 

Pain travels from the limbs to the spinal cord to the brain. The zona incerta reduces pain by filtering out or inhibiting sensory cues it deems unimportant before they pass on to the rest of the brain. The zona incerta allows only certain pain information to be experienced by the brain. The study, called "Zona Incerta: A Role in Central Pain," traced Central Pain Syndrome back to a malfunctioning zona incerta. The scientists found that the zona incerta in animals with Central Pain Syndrome is not inhibiting pain as it should. The zona incerta in these animals is allowing too much pain inforomation through to the rest of the brain, causing the animals to experience unusually high levels of pain.

 

Dr. Keller collaborated on the study with Scott M. Thompson, PhD, professor, Department of Phsyiology, Radi Masri, PhD, assistant professor at the University of Maryland Dental School, Jessica Lucas, graduate student in the Program in Neuroscience, and Raimi Quiton, PhD, academic fellow and Peter Murray, PhD, post-doctoral fellow, both from the Deparmtnet of Anatomy & Neurobiology. The study was funded by that National Instiute of Neurological Disorders and Stroke and the Christopher & Dana Reeve Foundation.

 

Central Pain Syndrome affects as many as 80 percent of patients with spinal cord injury, about 30 percent of multiple sclerosis patients and almost 10 percent of patients who have suffered a stroke. The pain associated with the syndrome can be a heightened sensitivity to ordinarily painless activities as simple as putting on clothes or experiencing the wind on the skin. The syndrome also causes spontaneous pain that occurs for no apparent reason and can be unrelenting. There is no treatment for the condition, and scientists have known little about the source of the pain until now.

 

Co-investigator Dr. Thompson recently completed a study with his associate, Gexin Wang, PhD, post-doctoral fellow, Department of Physiology, showing that animals with Central Pain Syndrome respond to a drug call ethosuximide, a US Food and Durg Administration-approved treatment for childhood epilepsy. Dr. Thompson's student found that ethosuximide appeared to calm the over-activity and excitability in the the thalamus that seems related to Central Pain Syndrome. Some of that excessive activity may be the result of inactivity in the zona incerta, according to Dr. Keller's and Dr. Thompson's latest joint study. "Our two studies examine areas of the brain that are very near each other, very similar and clearly related. We believe our two studies are basically indicating the same thing-that there is some imbalance of activity in the thalamus."

 

The scientists plan to continue their research to investigate new treatments and preventions for Central Pain Syndrome. Dr. Thompson will begin a study of ethosuximide in human patients very soon. Since that drug already has earned FDA approval for treating epilepsy, if it proves effective in Central Pain Syndrome it could be approved for treating that condition far more quickly than a new drug. Dr. Keller is planning to investigate other avenues as well. His study showed that, after an injury to the spinal cord, the zona incerta gradually stops working properly over a period of several weeks. Dr. Keller and his colleagues hope to find a way to intervene during those weeks and keep the zona incerta active. "We're considering options such as non-invasive brain stimulation, stem cell implants or even occupational therapy-exercises patients could do to stimulate the zona incerta," Dr. Keller said. " A successful treatment regimen one day could include a combination of exercises and drug therapy. We're hopeful we'll find relief for these patients, at last."