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Researchers pinpoint molecular basis for phantom pain
September 21, 2005Yale 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."
Yale University
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."
Yale University
Spinal Cord Injury Current Events and Spinal Cord Injury News RSSUCI embryonic stem cell therapy restores walking ability in rats with neck injuries
The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage.
Findings show nanomedicine promising for treating spinal cord injuries
Researchers at Purdue University have discovered a new approach for repairing damaged nerve fibers in spinal cord injuries using nano-spheres that could be injected into the blood shortly after an accident.
Researchers explore new ways to prevent spinal cord damage using a vitamin B3 precursor
Substances naturally produced by the human body may one day help prevent paralysis following a spinal cord injury, according to researchers at Weill Cornell Medical College. A recent $2.5 million grant from the New York State Spinal Cord Injury Research Board will fund their research investigating this possibility.
Master regulator found for regenerating nerve fibers in live animals
Researchers at Children's Hospital Boston report that an enzyme known as Mst3b, previously identified in their lab, is essential for regenerating damaged axons (nerve fibers) in a live animal model, in both the peripheral and central nervous systems.
Researchers find ways to encourage spinal cord regeneration after injury
Animal research is suggesting new ways to aid recovery after spinal cord injury. New studies demonstrate that diet affects recovery rate and show how to make stem cell therapies safer for spinal injury patients.
University of Louisville neuroscientists hope to get people walking again
Neuroscience researchers at the University of Louisville will be the only team collaborating with an international group of scientists that last week announced they had enabled paralyzed rats to walk while supporting their own weight.
UCLA scientists make paralyzed rats walk again after spinal-cord injury
UCLA researchers have discovered that a combination of drugs, electrical stimulation and regular exercise can enable paralyzed rats to walk and even run again while supporting their full weight on a treadmill.
arrow researcher finds natural hydrogel helps heal spinal cord
Research led by a scientist at the Barrow Neurological Institute at St. Joseph's Hospital and Medical Center has shown injecting biomaterial gel into a spinal cord injury site provides significantly improved healing.
UCSF researchers program cells to be remote-controlled by light
UCSF researchers have genetically encoded mouse cells to respond to light, creating cells that can be trained to follow a light beam or stop on command like microscopic robots.
Flips, flops and cartwheels
Geckos and other lizards have long been known for their incredible ability to shed their tails as a decoy for predators, but little is known about the movements and what controls the tail once it separates from the lizard's body.
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