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08-25-2003, 09:54 AM
http://www.sunspot.net/news/health/bal-te.pain25aug25,0,2751322.story?coll=bal-home-headlines
Medicine & Science
Real misery of phantom pain
Nerves: The body's attempt to rewire itself after a stroke, amputation or spine injury can lead to agony without any usual cause.
Sponsored by
By David Kohn
Sun Staff
August 25, 2003
Bob Lane thought he had survived almost unscathed. At first, the only damage from his 1999 stroke seemed to be reduced peripheral vision in one eye. But a few months later, the pain began.
It began as just an odd tingling in his left leg. But over several months, the sensation became more and more painful, until it was excruciating. The strangest part of the phenomenon: Nothing at all was wrong with his leg.
"It feels like my leg has been burned and I'm wearing sandpaper pants," says Lane, a retired college biology professor who lives in Bainbridge, Ga. Because the brush of a bedsheet can trigger the sensation, Lane rarely sleeps through the night. Even the breeze from a ceiling fan can bring on the pain.
Over the past 3 1/2 years, he has gone to a half-dozen doctors and tried a dozen different drugs, as well as acupuncture - to no avail. "It's frustrating," he says. "Somehow my brain is sending the wrong messages to my body."
Lane's experience is not unusual. Thousands of stroke victims every year suffer this mysterious pain. The problem is not limited to them - the malady afflicts hundreds of thousands of Americans, including those with spinal cord injuries, cancer, diabetes, multiple sclerosis and amputated limbs.
The syndrome is commonly known as "central pain" because it originates in the central nervous system - the spinal cord and brain - rather than in the limbs and trunk. It has confused and vexed doctors and patients for decades.
"We don't understand it very well, and we don't treat it very well," says Johns Hopkins Hospital neurosurgeon Dr. Frederick Lenz, a recognized specialist in central pain.
But in the past five years, researchers have begun to unravel exactly how the central nervous system perceives - and creates - pain. Scientists are using this knowledge to develop new treatments, which could eventually ease Lane's sandpaper sensation.
Those with central pain endure a range of agonizing, baffling sensations. Some describe feeling as if they were on fire, while others report a tingling coldness. One patient found that brushing his teeth sent awful pain to his arms.
"I get the feeling there are chunks of broken glass in parts of my body," says 38-year-old Lisa Bard, whose spinal cord was damaged in an accident this year. Bard, who lives in Germantown, has tried numerous drugs and therapies. None has done much to alleviate the pain, which flares up without warning.
Drugs that work well for "normal" pain, such as morphine, typically do little for the disorder. Unwilling or unable to face the excruciating suffering, a significant number of central pain patients commit suicide.
Until the 1950s, many physicians doubted that the mysterious malady even existed, attributing complaints to hypochondria or malingering. Even today, it is not unusual for doctors to question the reality of their patients' pain.
"Traditionally, physicians have been taught that if there's no sensory input, the pain isn't real," says anesthesiologist Dr. Christine Sang, a central pain expert at Harvard Medical School.
Researchers now know that central pain stems from misinterpreted signals in the central nervous system. "It's an illusion - a neural illusion," says neuroscientist Bob Yezierski. "You have a sensation that something is going on, but in fact nothing is going on. The only thing happening is an abnormal activation in the central nervous system."
For those with spinal cord injuries, central pain is particularly vexing: 60 percent to 90 percent of the 400,000 spinal cord injury patients in this country have the disorder. For many, this pain is more debilitating than the original injury - one study found that almost four in 10 patients would gladly trade pain relief for the chance to regain pre-injury movement.
For the past decade, Yezierski has studied how spinal cord injuries disturb pain transmission. In experiments on rats, he has found that after an injury, the spinal cord's main inhibitory circuitry breaks down, allowing pain-transmitting neurons to fire much more often than normal. "The brain interprets these abnormal discharges as pain," he says.
Yezierski, who directs the Comprehensive Center for Pain Research at the University of Florida, is trying to find ways to stop this neuronal machine gun. He's focusing on neurons that have the neurokinin-1 (NK-1) receptor, which seems to play a key role in sending central pain signals. He uses "molecular neurosurgery," attaching a neurotoxin to the neurotransmitter that activates NK--1.
When this neurotransmitter links with NK-1, the attached neurotoxin gets into the cell and kills it, thus eliminating the excessive pain signals. The early results are promising. In rats, the procedure "had a very significant effect on pain behavior," says Yezierski, who hopes to test the method in human trials.
The loss of inhibitory circuits is just one piece of the puzzle. Yale University scientists have found that once severed, spinal cord neurons try to reconnect themselves. They succeed, but often link with the wrong neurons.
"The wiring gets switched," says Yale neuroscientist Bryan Hains. "Instead of touch, the signal becomes pain."
This mis-wiring might help explain why those with the disorder can feel piercing pain in response to seemingly harmless stimuli such as clothing on skin.
Hains and his colleagues are trying to stop these garbled signals by clogging the sodium channel, a key structure in the neuron that sends electrical charges to other neurons. They have developed a drug to block these channels in certain pain receptors. When given to rats with injured spinal cords, the substance seems to sharply reduce pain.
Other researchers are focusing on the brain's role in central pain. Using cutting-edge brain imaging technology, researchers have found that a spinal cord injury can lead to changes in the brain itself.
Research on monkeys in the late 1990s suggests the damaged spinal cord sends fewer signals to the thalamus, the walnut-shaped brain region that receives and organizes almost all sensory input. Without input, the thalamus becomes hypersensitive, firing more frequently in response to smaller stimuli.
A similar alteration might occur in stroke victims, says University of Maryland, Baltimore pain researcher Joel Greenspan. He suspects that in the months after the stroke, healthy brain neurons sprout into damaged areas. These invading cells might misinterpret incoming signals, turning innocuous sensations into excruciating ones.
Greenspan and Lenz are trying to map brain areas where specific pain sensations occur. With such a map, doctors might one day be able to switch off particular sensations: Scientists at the University of California, San Francisco announced last month that they had injected a signal-blocking gene into the rat cortex, halting pain coming from a specific brain region.
For now, though, doctors must rely on a less exact method to stop the brain's aberrant pain signals.
Lenz and a few others around the country are trying a new surgical technique, in which electrodes are implanted above the motor cortex. Placed permanently inside the skull, the device sends a signal that seems to jam central pain messages. Lane, the retired professor, is considering the procedure, which succeeds about half the time.
How does this stimulation surgery work? No one really knows. Despite recent advances, central pain remains a daunting mystery. As Greenspan puts it: "This syndrome illustrates just how little we know about the human brain."
Copyright © 2003, The Baltimore Sun
Alan
Medicine & Science
Real misery of phantom pain
Nerves: The body's attempt to rewire itself after a stroke, amputation or spine injury can lead to agony without any usual cause.
Sponsored by
By David Kohn
Sun Staff
August 25, 2003
Bob Lane thought he had survived almost unscathed. At first, the only damage from his 1999 stroke seemed to be reduced peripheral vision in one eye. But a few months later, the pain began.
It began as just an odd tingling in his left leg. But over several months, the sensation became more and more painful, until it was excruciating. The strangest part of the phenomenon: Nothing at all was wrong with his leg.
"It feels like my leg has been burned and I'm wearing sandpaper pants," says Lane, a retired college biology professor who lives in Bainbridge, Ga. Because the brush of a bedsheet can trigger the sensation, Lane rarely sleeps through the night. Even the breeze from a ceiling fan can bring on the pain.
Over the past 3 1/2 years, he has gone to a half-dozen doctors and tried a dozen different drugs, as well as acupuncture - to no avail. "It's frustrating," he says. "Somehow my brain is sending the wrong messages to my body."
Lane's experience is not unusual. Thousands of stroke victims every year suffer this mysterious pain. The problem is not limited to them - the malady afflicts hundreds of thousands of Americans, including those with spinal cord injuries, cancer, diabetes, multiple sclerosis and amputated limbs.
The syndrome is commonly known as "central pain" because it originates in the central nervous system - the spinal cord and brain - rather than in the limbs and trunk. It has confused and vexed doctors and patients for decades.
"We don't understand it very well, and we don't treat it very well," says Johns Hopkins Hospital neurosurgeon Dr. Frederick Lenz, a recognized specialist in central pain.
But in the past five years, researchers have begun to unravel exactly how the central nervous system perceives - and creates - pain. Scientists are using this knowledge to develop new treatments, which could eventually ease Lane's sandpaper sensation.
Those with central pain endure a range of agonizing, baffling sensations. Some describe feeling as if they were on fire, while others report a tingling coldness. One patient found that brushing his teeth sent awful pain to his arms.
"I get the feeling there are chunks of broken glass in parts of my body," says 38-year-old Lisa Bard, whose spinal cord was damaged in an accident this year. Bard, who lives in Germantown, has tried numerous drugs and therapies. None has done much to alleviate the pain, which flares up without warning.
Drugs that work well for "normal" pain, such as morphine, typically do little for the disorder. Unwilling or unable to face the excruciating suffering, a significant number of central pain patients commit suicide.
Until the 1950s, many physicians doubted that the mysterious malady even existed, attributing complaints to hypochondria or malingering. Even today, it is not unusual for doctors to question the reality of their patients' pain.
"Traditionally, physicians have been taught that if there's no sensory input, the pain isn't real," says anesthesiologist Dr. Christine Sang, a central pain expert at Harvard Medical School.
Researchers now know that central pain stems from misinterpreted signals in the central nervous system. "It's an illusion - a neural illusion," says neuroscientist Bob Yezierski. "You have a sensation that something is going on, but in fact nothing is going on. The only thing happening is an abnormal activation in the central nervous system."
For those with spinal cord injuries, central pain is particularly vexing: 60 percent to 90 percent of the 400,000 spinal cord injury patients in this country have the disorder. For many, this pain is more debilitating than the original injury - one study found that almost four in 10 patients would gladly trade pain relief for the chance to regain pre-injury movement.
For the past decade, Yezierski has studied how spinal cord injuries disturb pain transmission. In experiments on rats, he has found that after an injury, the spinal cord's main inhibitory circuitry breaks down, allowing pain-transmitting neurons to fire much more often than normal. "The brain interprets these abnormal discharges as pain," he says.
Yezierski, who directs the Comprehensive Center for Pain Research at the University of Florida, is trying to find ways to stop this neuronal machine gun. He's focusing on neurons that have the neurokinin-1 (NK-1) receptor, which seems to play a key role in sending central pain signals. He uses "molecular neurosurgery," attaching a neurotoxin to the neurotransmitter that activates NK--1.
When this neurotransmitter links with NK-1, the attached neurotoxin gets into the cell and kills it, thus eliminating the excessive pain signals. The early results are promising. In rats, the procedure "had a very significant effect on pain behavior," says Yezierski, who hopes to test the method in human trials.
The loss of inhibitory circuits is just one piece of the puzzle. Yale University scientists have found that once severed, spinal cord neurons try to reconnect themselves. They succeed, but often link with the wrong neurons.
"The wiring gets switched," says Yale neuroscientist Bryan Hains. "Instead of touch, the signal becomes pain."
This mis-wiring might help explain why those with the disorder can feel piercing pain in response to seemingly harmless stimuli such as clothing on skin.
Hains and his colleagues are trying to stop these garbled signals by clogging the sodium channel, a key structure in the neuron that sends electrical charges to other neurons. They have developed a drug to block these channels in certain pain receptors. When given to rats with injured spinal cords, the substance seems to sharply reduce pain.
Other researchers are focusing on the brain's role in central pain. Using cutting-edge brain imaging technology, researchers have found that a spinal cord injury can lead to changes in the brain itself.
Research on monkeys in the late 1990s suggests the damaged spinal cord sends fewer signals to the thalamus, the walnut-shaped brain region that receives and organizes almost all sensory input. Without input, the thalamus becomes hypersensitive, firing more frequently in response to smaller stimuli.
A similar alteration might occur in stroke victims, says University of Maryland, Baltimore pain researcher Joel Greenspan. He suspects that in the months after the stroke, healthy brain neurons sprout into damaged areas. These invading cells might misinterpret incoming signals, turning innocuous sensations into excruciating ones.
Greenspan and Lenz are trying to map brain areas where specific pain sensations occur. With such a map, doctors might one day be able to switch off particular sensations: Scientists at the University of California, San Francisco announced last month that they had injected a signal-blocking gene into the rat cortex, halting pain coming from a specific brain region.
For now, though, doctors must rely on a less exact method to stop the brain's aberrant pain signals.
Lenz and a few others around the country are trying a new surgical technique, in which electrodes are implanted above the motor cortex. Placed permanently inside the skull, the device sends a signal that seems to jam central pain messages. Lane, the retired professor, is considering the procedure, which succeeds about half the time.
How does this stimulation surgery work? No one really knows. Despite recent advances, central pain remains a daunting mystery. As Greenspan puts it: "This syndrome illustrates just how little we know about the human brain."
Copyright © 2003, The Baltimore Sun
Alan