2003 Director's Summary Synopsis

CHARACTERIZING MECHANISMS OF NEUROPATHIC PAIN
Mary J. Eaton, Ph.D. • Jacqueline Sagen, Ph.D.

Of the several pain syndromes associated with SCI, pain related directly to the neurological consequences of the injury is called central neuropathic pain. Such pain (burning, piercing or radiating sensation) is often experienced below the level of injury in areas where normal sensory functions are disrupted. Since conventional treatments for neuropathic pain are ineffective, basic science research has focused on understanding the causes of and developing new treatment strategies for pain syndromes.

Researchers have theorized that pain may result when nerves below the injury become hypersensitive, presumably because of a loss of input from nerves in the brain that release and regulate chemicals. Dr. Mary Eaton, collaborating with colleagues at the University of Texas Medical Branch, studied the effect of a transplantation of cells that release serotonin and brain derived nerve growth factor. Their results show a reduction of the hyperexcitability caused by the injury and suggest cell transplants such as these may be useful in treating chronic neuropathic pain. To ready treatment approaches for testing in humans, Dr. Eaton will soon conduct other collaborative research with colleagues in France.

Previous research in animals has also shown that implanting chromaffin cells at the surface of the spinal cord can alleviate many symptoms of chronic pain. Chromaffin cells, found in the center of the adrenal glands, secrete a cocktail of various analgesic substances. In this study, Dr. Jacqueline Sagen evaluated the efficacy of NMDA receptor antagonists, one of the components of the cocktail, to obtain a better understanding of the mechanism by which chromaffin cells exert their analgesic effect. The intervention, which blocks certain chemical interactions, resulted in partial reversal of specific pain characteristics. These results add to the knowledge needed to develop new multifaceted treatments for neuropathic pain, and suggest that complete pain alleviation will likely require a combination of components in the cellular cocktail.

Synopsis Publications

 Hains BC, Johnson KM, Eaton MJ, Willis WD, Hulsebosch CE (2003) Serotonergic neural precursor cell grafts attenuate bilateral hyperexcitability of dorsal horn neurons after spinal hemisection in rat. Neurosci 116:1097-1110.

 Hama A, Woon Lee J, Sagen J (2003) Differential efficacy of intrathecal NMDA receptor antagonists on inflammatory mechanical and thermal hyperalgesia in rats. Eur J Pharmacol 459:49-58.