New Haven, Conn.-Yale researchers report the first evidence that phantom pain following spinal cord injury is the result of hypersensitive neurons in the thalamic region of the brain that can be suppressed with specially designed molecular agents.
"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 injury to the spinal cord and that suppressing the activity of Nav1.3 in these neurons can mitigate pain," said senior author Stephen Waxman, M.D., professor and chair of neurology and director of the Veterans Administration Rehabilitation Research and Development Center in West Haven. "Although these studies must be validated in higher-order animals before testing in humans, this represents an important step forward in the understanding and treatment of phantom pain."
The study was supported by the Medical Research Service and Rehabilitation Research and Development Service, Department of Veterans Affairs, the United Spinal Association, the Paralyzed Veterans of America and Pfizer Inc.
Brain (August 18, 2005, online)
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