"A majority of people with spinal cord injury and limb amputations experience phantom sensations of excruciating pain at or below the level of their paralysis or loss," said Bryan Hains, associate research scientist and co-author of the study.

Typically, the perception of pain travels through three orders of neurons. The first order neurons carry signals from the periphery to the spinal cord, the second order neurons relay this information from the spinal cord to the thalamus and the third order neurons transmit the information from the thalamus to the primary sensory cortex where the information is processed, resulting in the "feeling" of pain.

The study reports that in rats with spinal cord injury, third order neurons within the thalamus spontaneously and abnormally fire signals in the absence of any incoming signals from the first order neurons. It also reports that these rogue neurons contain abnormally high levels of a particular type of sodium channel, called Nav1.3. Sodium channels serve as batteries during the conduction of nerve signals.

"Abnormal presence of Nav1.3 in these neurons has been linked to changes in their physiological temperament. They are hypersensitive and spontaneously fire signals at higher-than-normal rates, even in the absence of a painful stimulus," Hains said.

The researchers designed targeted molecular agents against Nav1.3 and injected them into the spinal fluid of the injured rats. This produced a significant reduction in the presence of Nav1.3 in second and third order neurons accompanied by a reduction in signals that they produced.

"This study is the first to show that thalamic neurons contain abnormally high levels of Nav1.3 after i
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Contact: Jacqueline Weaver
jacqueline.weaver@yale.edu
203-432-8555
Yale University
20-Sep-2005