For release: Thursday, October 9, 1997
Investigators have isolated a tiny population of neurons, located in the spinal cord, that together form a major portion of the pathway responsible for carrying persistent pain signals to the brain. When given injections of a lethal chemical cocktail, the cells, whose sole function is communication of this type of pain, are killed off.
"What we've accomplished is chemical ablation of the pathway responsible for hypersensitive pain responses," said Patrick Mantyh, Ph.D., of the VA Medical Center in Minneapolis and the University of Minnesota who headed the study. "We were able to administer a potent cocktail and specifically channel it to certain cells, disabling them." The paper appears in the October 10, 1997, issue of Science.*
The investigators used a neutralizing toxin comprised of substance P -- a neurotransmitter linked to pain -- and the chemical saporin and injected it to into the spinal cords of rats through surrounding cerebrospinal fluid.
"The treatment served as a cushion against pain and, even better, did not affect any of the surrounding cells," said Dr. Mantyh. "The animals acted completely normal except that they no longer exhibited or had a hypersensitive pain response."
Receptors for substance P -- large molecules found on the surface of the cells -- served as portals for the compound's entry. Within days, the targeted neurons, located in the outer layer of the spinal cord along its entire length, absorbed the compound and were neutralized.
Scientists already know that substance P plays a role in pain, but its specific role in signaling, relaying or conveying pain signals is not entirely understood. Investigators believe that any beneficial effects resulting from targeted damage to neurons point to the neurotransmitter's critical role in communicating pain information from the spinal cord to the thalamus, the brain's pain center. Hypersensitivity to pain is the condition of an exaggerated painful response to innocuous stimulation, such as warmth or light touch.
The concept of using specific receptors as portals for the introduction of therapeutic compounds may pave the way for a new pain therapy. Such compounds might be first introduced through a lumbar puncture, a technique commonly used for collecting spinal fluid. The compounds would then serve to relay information through the spinal cord to the thalamus, thus blocking pain signals.
"We expect that any treatment based on this procedure would enable patients to avoid many of the side effects associated with pain medicine, including sedation and addiction," according to Dr. Mantyh.
"This is a tremendous payoff for the long-term investment the National Institute of Neurological Disorders and Stroke has made in pain research," says Cheryl Kitt, Ph.D., Health Scientist Administrator at the NINDS, which supported Dr. Mantyh's work. "There is a very real possibility that over the next 5 to 10 years this finding will revolutionize our thinking about new treatment strategies for persistent pain."
Dr. Mantyh and his team plan additional studies of cell populations and neurotransmitters found in the spinal cord.
"The next step will be to determine how long the therapy relieves the pain in rats, and then if relief is stable over several months, we hope to try it on patients with pain that isn't well managed by opiates, such as the pain associated with cancer," said Dr. Mantyh. "Any new therapies based on this work will have to first be tested carefully and will be subject to review and approval by the FDA."
The NINDS, one of the National Institutes of Health located in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous system and a lead agency for the Congressionally designated Decade of the Brain.
*Mantyh, P.W.; Rogers, S.D.; Honore, P.; Allen, B.J.; Ghilardi, J.R.; Li, J.; Daughters, R.S.; Lappi, D.A.; Wiley, R.G.; and Simone, D.A. "Inhibition of Hyperalgesia by Ablation of Lamina I Spinal Neurons Expressing the Substance P Receptor." Science, Vol. 278, October 10, 1997, p. 275-279.
Originally prepared by Stephanie Clipper, NINDS Office of Communications and Public Liaison
Last Modified August 7, 2009