A new study by Yale researchers has found a possible explanation for chronic pain in patients with spinal cord injuries.
Conduction of signals in nerve cells is controlled by molecular “batteries” called sodium channels. The study found that injured nerve cells tend to produce more sodium channels that transmit pain signals to the brain, resulting in chronic pain after injury.
The study uses previous findings by Bryan Hains, a postdoctoral fellow in neurology at the Veterans Administration Rehabilitation Research and Development Center in West Haven and in the Yale School of Medicine. This research detected abnormally high levels of the sodium channel, Nav 1.3, in the pain-signaling nerve cells after spinal cord injury in rats.
Professor Stephen Waxman, the chair of neurology at the Yale School of Medicine who co-authored the study, said each channel serves a different function, and the activation of the pain channels results in excessive pain sensations.
“Different neurons speak different languages and fire different signals,” Waxman said. “We found that after nerve damage, nerves shut off the genes for some sodium channels and turn on the genes for others — pain-signaling nerve cells that should normally be quiet were now firing repeatedly.”
In this most recent study, Hains and Waxman treated damaged nerve cells with specific molecules designed to block the production of these channels, which resulted in decreased pain.
The study’s findings suggest a means of preventing such pain lies in preventing the production of these specific sodium channels.
“[An injured spinal cord] produces the channels that shouldn’t be there — and brain interprets that as pain,” Waxman said. “[Hains used a technology] that lets him shut off the gene that is turned on, and then the pain cells stop chattering inappropriately.”
Waxman said these findings begin to address a serious unsolved problem in medical treatment.
“In general, the issue of pain after nerve damage is a huge unmet need in medicine,” he said.
However, Waxman said the treatment is only in its beginning stages and should not be extrapolated to give false hope to patients and their families. He added that the study only definitively offers a possible explanation for pain.
“We now know at least in principle that silencing this gene abolishes the pain,” Waxman said. “The next question is, are there ways that are clinically safe to silence the gene — we’re beginning to work on that.”
Waxman said that while the treatment works in theory, applying it to patients could take many years.
“It’s safe to say that we uncovered a previously unsuspected molecule that appears to play a key role in generating pain in spinal cord injuries.”
Future studies will involve animals closer to human physiology, slowly approaching clinical trials in humans.
“The first step is to explore these ideas in rats, which is what we did,” Hains said. “The next step is to move to an animal close to humans like a cat or a primate model, and if the therapy works in monkeys or cats, the next step is to initiate a clinical trial, but that’s many years down the road.”
The study was funded by the Medical Research Service and Rehabilitation Research and Development Service of the Department of Veterans Affairs, the Eastern Paralyzed Veterans Association, the Paralyzed Veterans of America, The Christopher Reeve Paralysis Foundation, and the National Institute of Neurological Disorders and Stroke.