CHICAGO – Chronic pain that persists long after the original injury has healed may stem from an old memory trace that gets stuck in the brain’s cortex, a Chicago researcher has found. And a drug that targets the cortex can lessen that pain, at least in rats.
The discovery has to be confirmed in human trials but could offer relief to millions of people who are not helped by traditional painkillers.
“You can think of chronic pain as the inability to turn off the memory of the pain,” said Vania Apkarian, a professor of physiology at Northwestern University.
His previous studies with magnetic resonance imaging suggested that that memory resides in the prefrontal cortex, the site of emotional and cognitive learning. A drug called D-cycloserine, used to treat phobic behavior, activates a receptor in that part of the brain and “interferes with long-term memory acquisition and forgetting. … So we decided to test the idea that this drug might have an effect on chronic pain,” Apkarian said.
The results of his experiment have been published online and will appear in the journal Pain this fall.
Most researchers try to control pain by blocking the sensory input to the brain, Apkarian said. But he believes easing the pain’s memory trace, with its emotional overlay, may be more effective.
To test that idea, Apkarian first induced chronic pain in lab rats by severing two branches of their left sciatic nerve but leaving the third branch intact.
After the injuries healed, his research team gave D-cycloserine to some of the rats and compared their behavior to that of untreated animals when they were exposed to painful stimuli.
What they discovered appears to confirm the notion that chronic pain has both a sensory component and an emotional component.
When they measured how quickly the animals withdrew their injured hind leg, an indication of sensory pain, they found that the drug decreased pain by about 30 percent. But when they looked at the animals’ interaction with their environment, a reflection of emotional suffering, they found a much greater effect.
The team tested the rats in a special two-chamber compartment, with one room dark and the other bright. As nocturnal animals, rats naturally prefer to be in the dark. But if a researcher pricked their sensitive limbs, they would flee to the bright room. However, when they were treated with D-cycloserine, the animals remained in the dark chamber.
“We continue to prick the foot – and they still feel it, because they pull their foot away – but they don’t seem to mind anymore,” Apkarian said. “We believe the emotional component of the pain has become much less.”
In the human world, Apkarian said, patients suffer in large part because of the emotional overlay of continuous pain, which distracts them and impairs their everyday ability to function.
“We predict that if we give this drug, they’ll say, “I still have pain, but it doesn’t bother me as much,”‘ he said.
If he’s right, patients with chronic pain might be able to lower the dose of conventional painkillers they would otherwise have to take. D-cycloserine, an antibiotic in use since 1940, has few side effects, Apkarian said. And in his lab rats, the pain relief, though not immediate, lasted long after the animals stopped taking the drug.
“Anything that helps decrease narcotic intake is going to be useful,” said Peggy Mason, a professor of neurobiology at the University of Chicago, who was not connected to Apkarian’s study.
Mason expressed cautious optimism about the approach, saying: “Neuropathic pain is a devastating problem. It can alter someone’s quality of life profoundly, (even) drive them to suicide. If a treatment could help any portion of the chronic-pain population, it would be terrific, and it looks like this might be able to help some people.”
Dr. Howard Fields, a neurologist at the University of California at San Francisco, praised the work, saying, “Maybe this will be really a very valuable medication.”
Apkarian said Northwestern will launch a clinical trial of D-cycloserine “very soon.”