Research progresses, slowly, into the causes of and treatments for neuropathic post-SCI pain.
By Alan Krawitz
In life, there are various types of pain that run the gamut from minor inconvenience to disabling. And then, almost in a class by itself, is neuropathic pain, a severe, crippling type of pain that many people with spinal cord injuries often experience. Unfortunately, all pain is not created equal. In fact, the latest research says that more than half of all people with nerve and spinal cord damage experience damage to nerve fibers, which results in neuropathic pain.
“Many have described neuropathic pain as being, alternately, burning, searing and excruciating,” according to Dr. Lakshmi Bangalore, scientific liaison officer for the Center for Neuroscience and Regeneration Research (CNRR) at Yale University and at the VA Medical Center in West Haven, Connecticut. The center is sponsored and supported as a joint effort, by United Spinal Association and Paralyzed Veterans of America. “To some, neuropathic pain is so severe that they would trade their motor recovery for some relief. Others have even considered suicide,” Dr. Bangalore says.
Understanding the Causes
Making matters worse, many of the medications currently available to treat neuropathic pain are only partially effective and produce many unwanted side effects. Dr. Bangalore cited morphine as one such drug treatment that is fraught with problems.
However, Dr. Bangalore says that regardless, scientists are beginning to understand more and more some of the causes of neuropathic pain and uncover ways to manage it both safely and efficiently. “Although most current research is still very basic and investigative in nature, we continue to move forward, progress and explore new avenues. Much of the research being done now will enable new treatments to progress to the next level.”
Concerning research into new treatments for neuropathic pain, Dr. Bangalore says that the next generation of medications would be highly target- specific with little or no side effects. “For example,” Dr. Bangalore says, “a particular type of sodium channel called Nav 1.3 is present in abnormally high levels in pain-signaling neurons after SCI.” Sodium channels are proteins in the membranes of certain cells, like neurons, that can be stimulated to allow positively charged sodium ions to pass through. Too much Nav 1.3 in the neuronal membrane causes the nerves to become “hyper-responsive” and fire impulses at higher-than-normal rates. “Normal stimuli then become extremely painful,” Dr. Bangalore says.
“We showed that injecting rats with molecules specially designed to target the problem sodium channel resulted in decreased production of the Nav 1.3 sodium channels, less hyper-responsiveness of the pain-signaling nerve cells within the spinal cord, and reduced pain-related behaviors,” Dr. Bangalore explains. But, it was reported that pain returned when the treatment was stopped.
Asked about other promising research in the area of pain management, Dr. Bangalore discussed the importance of certain types of immune cells in the body called microglia, which are non-neuronal cells that play important roles in the central nervous system, for example, in the production of the nerve cell’s “insulation” material myelin. “Our studies also suggest an important role for activated microglia of the immune system in the maintenance of pain after SCI and support for the newly emerging role of non-neuronal immune cells as a contributing factor in post-SCI pain. Specifically, we showed that T9 SCI in rats can turn on microglia in the lumbar dorsal horn (a region within the spinal cord) and that this microglial activation contributes to neuronal hyperresponsiveness and alterations in pain-related behavior. Pharmacological suppression of microglial activation with minocycline (a type of anti-biotic) decreased pain-related behavior.”
Dr. Bangalore reported that these findings suggest that the drug minocycline may merit additional study as a possible therapeutic agent for the treatment of post-SCI pain. However, she also cautions that despite their potential, the above treatments–utilizing animal studies–must be replicated and tested in higher-order animals before being tested on humans.
So, while Dr. Bangalore remains sanguine regarding the development of new medications and therapies for the treatment of post-SCI pain, she still tempers her enthusiasm. “We’re still a long way from developing new treatments,” she cautions. Nevertheless, Dr. Bangalore and other researchers say that much progress has already and will continue to be made. “A mere two decades ago, SCIs and disorders were regarded as untreatable,” Dr. Bangalore notes. “Today, as a result of CNRR, a cure for SCI is seen as an achievable goal.”
Alan Krawitz is communications manager.
