Yale Bulletin and Calendar

November 14, 2003|Volume 32, Number 11

Scientists discover method that may
reduce pain from spinal cord injury

The burning, vise-like pain experienced by most people with spinal cord injuries results from overly sensitized nerve cells, and this activity can be blocked by administering specially designed molecules, according to Yale researchers.

These results for the first time implicate sodium channels -- molecular batteries necessary for conduction of nerve signals -- in severe pain following spinal cord injury. The findings also suggest a way to treat this pain by blocking the production of the specific sodium channels, report the authors in the October issue of the Journal of Neuroscience.

Spinal cord injury can result in hypersensitivity of pain-signaling nerve cells within the spinal cord. In his study with rats, Bryan Hains, a postdoctoral fellow in the Department of Neurology and at the Veterans Administration Rehabilitation Research and Development Center in West Haven, found a particular type of sodium channel, Nav 1.3, to be present in abnormally high levels within the pain-signaling nerve cells following spinal cord injury. These channels cause the nerve cells to become hypersensitive, allowing them to fire signals at higher-than-normal rates. Normal stimuli then become extremely painful.

Next, Hains and Stephen Waxman, professor and chair of neurology and senior author of the study, injected the rats with specially designed molecules, "antisense- oligonucleotides," targeting the problem sodium channel. The injection resulted in decreased production of the Nav 1.3 sodium channels, less hypersensitivity of the pain-signaling nerve cells within the spinal cord, and reduced pain-related behaviors. The pain returned when the treatment was stopped.

"These results demonstrate for the first time that an easily targeted molecule can have dramatic effect on pain after spinal cord injury," Hains says, adding that this finding is "very exciting." However, despite their potential, the results must be replicated and tested in higher-order animals before testing in humans, he notes.

The research was supported by the Medical Research Service and Rehabilitation Research and Development Service, Department of Veterans Affairs; the Eastern Paralyzed Veterans Association; the Paralyzed Veterans of America; The Christopher Reeve Paralysis Foundation and the National Institutes of Health-National Institute of Neurological Disorders and Stroke.

-- By Jacqueline Weaver

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