Researchers Pinpoint Molecular Basis For Phantom Pain Following Spinal Cord Injury

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

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

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

"Abnormal presence of Nav1.3 in these neurons has been linkedto changes in their physiological temperament. They are hypersensitiveand spontaneously fire signals at higher-than-normal rates, even in theabsence of a painful stimulus," Hains said.

The researchers designed targeted molecular agents againstNav1.3 and injected them into the spinal fluid of the injured rats.This produced a significant reduction in the presence of Nav1.3 insecond and third order neurons accompanied by a reduction in signalsthat they produced.

"This study is the first to show that thalamic neurons containabnormally high levels of Nav1.3 after injury to the spinal cord andthat suppressing the activity of Nav1.3 in these neurons can mitigatepain," said senior author Stephen Waxman, M.D., professor and chair ofneurology and director of the Veterans Administration RehabilitationResearch and Development Center in West Haven. "Although these studiesmust be validated in higher-order animals before testing in humans,this represents an important step forward in the understanding andtreatment of phantom pain."

The study was supported by the Medical Research Service andRehabilitation Research and Development Service, Department of VeteransAffairs, the United Spinal Association, the Paralyzed Veterans ofAmerica and Pfizer Inc.

Brain (August 18, 2005, online)