Researchers are beginning to understand the paradox of pain in people with SCI.
A common misconception about people with spinal disabilities is that, because a person lacks sensation in certain areas of his or her body, that person cannot feel physical pain in those places. Unfortunately, this is not true.
“The fact that one loses normal sensation does not mean that one will not have abnormal sensations. Pain after spinal cord and nerve injury is an immensely important medical target and an unmet medical need,” says Dr. Stephen Waxman, director of the Center for Neuroscience and Regeneration Research at Yale University and at the VA Medical Center in West Haven, Connecticut. The center is sponsored and supported as a collaborative effort, by United Spinal Association and Paralyzed Veterans of America.
“We see spinal cord injured patients with pain below the level of the injury, at the level and above it,” Dr. Waxman says. “What we know is that, in some cases, after both spinal cord and nerve injury, pain arises from the inappropriate firing of pain-signaling neurons just outside of the spinal cord and, higher up within the pain pathway, within the spinal cord itself. Pain-signaling neurons that should be silent start to fire spontaneously and, since these neurons are meant to signal pain, the brain interprets the firing as pain.” Dr. Waxman likens this to static on a radio. “It’s not that nothing is coming through. The static itself can be unpleasant.” He notes that, “There’s a major effort within our Research Center aimed at finding what’s causing those neurons to buzz like that, so that we can turn off the abnormal activity.”
A number of laboratories are looking for approaches that will effectively deal with the chronic pain that can accompany SCI. “We have had a major research program in this area since 1990, when an individual with SCI asked us whether, in addition to focusing on a cure for his paralysis, we might attempt to find more effective treatments for his pain. We’ve taken a very fundamental approach, utilizing the fruits of the molecular revolution to understand precisely what happens after spinal cord injury, and what causes pain,” he explains. “We’ve identified the specific nerve cells, next to and within the spinal cord, that become hyperexciteable and induce pain after nerve injury and SCI. Then, we’ve asked what molecules within these nerve cells cause them to become hyperexciteable. We’ve identified those molecules, called sodium channels, and they act as molecular batteries for nerve impulses. There are ten different types of sodium channels, and we’ve found that, after injury, cells in the spinal cord produce a sodium channel that shouldn’t be there.”
This is called a Type III sodium channel and it causes nerve impulses to fire when they shouldn’t. “We can use very highly targeted molecular techniques on animals to turn off the gene that’s producing those channels after they are inappropriately produced following SCI. When we turn off the gene, the channels aren’t produced any longer and the cells are no longer hyperexcitable, so the animals no longer have pain. When we let the gene turn back on, the hyperexcitability goes away, and the pain comes back. We don’t have a cure yet, but this gives us a very well-defined molecular target, so we feel that we now understand neuropathic pain after spinal cord injury very well.”
So, what is a patient with SCI with chronic pain to do? Intrathecal therapy, whereby drugs are inserted via a catheter, is one effective, yet still imperfect, option. “Certainly, we hope to develop a therapy that will not require a catheter to be put into the spinal canal. The fact that so many people continue to have pain, no matter what they’re treated with, underscores the fact that there is a pressing need for better treatments, and I’m confident that they will be developed in the not-too-distant future.”
One newly approved drug, Prialt, is a derivative of a toxin produced by the cone snail. Interestingly, the toxin was proven useful to mute the signals in the brain that register pain. “A variety of experiments were carried out, first in animals, then in humans, showing that if you put one particular component of this snail toxin, called a conotoxin, into the spinal fluid, it will lessen pain signaling,” Dr. Waxman explains. Prialt is placed in a classification of drugs called calcium channel-blockers. “It’s not entirely clear why Prialt works on pain, because calcium channels are involved in a lot of different functions, one of the most important of which is synaptic activity. At first sight, you might think that, by turning off synaptic activity, you would make patients confused, or even stuporous.”
“One goal of research in spinal cord injury is to restore motor function,” states Dr. Waxman. “We want to restore the ability to walk, to use the hands, to write, to do all the things that we would like to do motorically. We also want to restore sensory loss. But, in addition, we want to solve the problem of pain, which is like an invisible epidemic. Some people with spinal cord injury have pain that is so significant that they say they would trade any chance of motor recovery for a chance to get rid of their pain. It can often be devastating to them. The good news is that, now that we understand the molecular basis for pain following SCI, we are in a position to try to do something about it. ”
Discovering new treatments for disorders such as chronic pain is not easy. Despite this fact, Dr. Waxman is optimistic about the future of pain management for those with spinal cord and nerve injuries. “Ten years from now, I think there is a good chance that we’ll have new and much better classes of medications for pain. We’re working 24/7 to make that happen.”
Physical pain is an awful fact of life that we all must face. With such diligence and energy being applied to this facet of SCI, perhaps relief for those who are currently suffering will soon become a reality.
Lori A. Wood is a frequent contributor to Orbit.
