Showing posts with label Neuroscience. Show all posts
Showing posts with label Neuroscience. Show all posts

Daily Science Journal (Feb. 7, 2008) — People with unrelenting pain don't only suffer from the non-stop sensation of throbbing pain. They also have trouble sleeping, are often depressed, anxious and even have difficulty making simple decisions.

Comparison of brains. These images show the brain from the left side, demonstrating striking differences between chronic pain patients and healthy subjects. They illustrate with colors how much activation (red-yellow) or deactivation (dark/light blue) was found at each location. (Credit: Image courtesy of Northwestern University)

In a new study, investigators at Northwestern University's Feinberg School of Medicine have identified a clue that may explain how suffering long-term pain could trigger these other pain-related symptoms.


Researchers found that in a healthy brain all the regions exist in a state of equilibrium. When one region is active, the others quiet down. But in people with chronic pain, a front region of the cortex mostly associated with emotion "never shuts up," said Dante Chialvo, lead author and associate research professor of physiology at the Feinberg School. "The areas that are affected fail to deactivate when they should."

They are stuck on full throttle, wearing out neurons and altering their connections to each other.

This is the first demonstration of brain disturbances in chronic pain patients not directly related to the sensation of pain.

Chialvo and colleagues used functional magnetic resonance imaging (fMRI) to scan the brains of people with chronic low back pain and a group of pain-free volunteers while both groups were tracking a moving bar on a computer screen. The study showed the pain sufferers performed the task well but "at the expense of using their brain differently than the pain-free group," Chialvo said.

When certain parts of the cortex were activated in the pain-free group, some others were deactivated, maintaining a cooperative equilibrium between the regions. This equilibrium also is known as the resting state network of the brain. In the chronic pain group, however, one of the nodes of this network did not quiet down as it did in the pain-free subjects.

This constant firing of neurons in these regions of the brain could cause permanent damage, Chialvo said. "We know when neurons fire too much they may change their connections with other neurons and or even die because they can't sustain high activity for so long," he explained.

'If you are a chronic pain patient, you have pain 24 hours a day, seven days a week, every minute of your life," Chialvo said. "That permanent perception of pain in your brain makes these areas in your brain continuously active. This continuous dysfunction in the equilibrium of the brain can change the wiring forever and could hurt the brain."

Chialvo hypothesized the subsequent changes in wiring "may make it harder for you to make a decision or be in a good mood to get up in the morning. It could be that pain produces depression and the other reported abnormalities because it disturbs the balance of the brain as a whole."

He said his findings show it is essential to study new approaches to treat patients not just to control their pain but also to evaluate and prevent the dysfunction that may be generated in the brain by the chronic pain.

The study will be published Feb. 6 in The Journal of Neuroscience. Chialvo's collaborators in this project are Marwan Baliki, a graduate student; Paul Geha, a post-doctoral fellow, and Vania Apkarian, professor of physiology and of anesthesiology, all at the Feinberg School.

Adapted from materials provided by Northwestern University.



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Daily Science Journal (Feb. 1, 2008) — In the first study to use imaging technology to see what goes on in the brain when we scratch, researchers at Wake Forest University Baptist Medical Center have uncovered new clues about why scratching may be so relieving -- and why it can be hard to stop.

"Our study shows for the first time how scratching may relieve itch," said lead author Gil Yosipovitch, M.D., a dermatologist who specializes in itch. "It's important to understand the mechanism of relief so we can develop more effective treatments. For some people, itch is a chronic condition that affects overall health."


The study involved 13 healthy participants who underwent testing with functional magnetic resonance imaging (MRI) technology that highlights areas of the brain activated during an activity. Participants were scratched on the lower leg with a small brush. The scratching went on for 30 seconds and was then stopped for 30 seconds -- for a total of about five minutes.

"To our surprise, we found that areas of the brain associated with unpleasant or aversive emotions and memories became significantly less active during the scratching," said Yosipovitch. "We know scratching is pleasurable, but we haven't known why. It's possible that scratching may suppress the emotional components of itch and bring about its relief."

The reduced brain activity occurred in the anterior cingulate cortex, an area associated with aversion to unpleasant sensory experiences, and the posterior cingulate cortex, which is associated with memory. When participants reported that the scratching felt most intense, activation in these areas was lowest.

Yosipovitch said patients occasionally report that intense scratching -- to the point of drawing blood -- is the only thing that relieves chronic itch.

"This is the first real scientific evidence showing that itch may be inhibited by scratching," he said. "Of course, scratching is not recommended because it can damage the skin. But understanding how the process works could lead to new treatments. For example, drugs that deactivate this part of the brain might be effective."

The imaging studies also showed that some areas of the brain were made more active by the scratching, including the secondary somatosensory cortex, a sensory area involved in pain, and the prefrontal cortex, which is associated with compulsive behavior.

"This could explain the compulsion to continue scratching," said Yosipovitch.

One drawback to the study is that the scratching occurred in the absence of itch. Yosipovitch's team is continuing the research by evaluating whether the findings will apply to chronic itch.

Understanding more about chronic itch is important, Yosipovitch said, noting that more than 30 million Americans suffer from eczema and that almost half (42 percent) of kidney dialysis patients are bothered by moderate to severe itch. In fact, those kidney dialysis patients with itch have a 17 percent higher mortality rate, likely from a loss of sleep, according to a report in Nephrology Dialysis Transplantation.

The work is reported online in the Journal of Investigative Dermatology and will appear in a future print issue.

The study was supported by the National Institutes of Health and the Center for Biomolecular Imaging of Wake Forest. Co-researchers were Yozo Ishuiji,MD, Tajesh Patel, M.D., Maria Isabel Hicks, M.D., Yoshitetsu Oshiro, M.D., Robert Kraft, Ph.D., Erica Winnicki, M.D., and Robert C. Coghill, Ph.D., senior author, all from Wake Forest.

Adapted from materials provided by Wake Forest University Baptist Medical Center, via EurekAlert!, a service of AAAS.



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Daily Science Journal (Jan. 30, 2008) — The potential of carbon nanotubes to diagnose and treat brain tumors is being explored through a partnership between NASA's Jet Propulsion Laboratory, Pasadena, Calif., and City of Hope, a leading cancer research and treatment center in Duarte, Calif.

Benham Badie, M.D., director of the Department of Neurosurgery and the Brain Tumor program at City of Hope, performs a minimally invasive procedure to surgically remove a pituitary tumor. Nanotube technology may help in the development of new treatments that would require only minimally invasive procedures no matter the location of the brain tumor. (Credit: City of Hope)

Nanotechnology may help revolutionize medicine in the future with its promise to play a role in selective cancer therapy. City of Hope researchers hope to boost the brain's own immune response against tumors by delivering cancer-fighting agents via nanotubes. A nanotube is about 50,000 times narrower than a human hair, but it length can extend up to several centimeters.


If nanotube technology can be effectively applied to brain tumors, it might also be used to treat stroke, trauma, neurodegenerative disorders and other disease processes in the brain, said Dr. Behnam Badie, City of Hope's director of neurosurgery and of its brain tumor program.

"I'm very optimistic of how this nanotechnology will work out," he said. "We are hoping to begin testing in humans in about five years, and we have ideas about where to go next."

The Nano and Micro Systems Group at JPL, which has been researching nanotubes since about 2000, creates these tiny, cylindrical multi-walled carbon tubes for City of Hope.

City of Hope researchers, who began their quest in 2006, found good results: The nanotubes, which they used on mice, were non-toxic in brain cells, did not change cell reproduction and were capable of carrying DNA and siRNA, two types of molecules that encode genetic information.

JPL's Nano and Micro Systems Group grows the nanotubes on silicon strips a few square millimeters in area. The growth process forms them into hollow tubes as if by rolling sheets of graphite-like carbon.

Carbon nanotubes are extremely strong, flexible, heat-resistant, and have very sharp tips. Consequently, JPL uses nanotubes as field-emission cathodes -- vehicles that help produce electrons -- for various space applications such as x-ray and mass spectroscopy instruments, vacuum microelectronics and high-frequency communications.

"Nanotubes are important for miniaturizing spectroscopic instruments for space applications, developing extreme environment electronics, as well as for remote sensing," said Harish Manohara, the technical group supervisor for JPL's Nano and Micro Systems Group.

Nanotubes are a fairly new innovation, so they are not yet routinely used in current NASA missions, he added. However, they may be used in gas-analysis or mineralogical instruments for future missions to Mars, Venus and the Jupiter system.

JPL's collaboration with City of Hope began last year, after Manohara, Badie and Dr. Babak Kateb, City of Hope's former director of research and development in the brain tumor program, discussed using nanostructures to better diagnose and treat brain cancer. Badie said his team's nanomedical research continues, and the next goal will be to functionalize and attach inhibitory RNA to the nanotubes and deliver it to specific areas of the brain.

The JPL and City of Hope teams published the results of the study earlier this year in the journal NeuroImage.

Badie says that JPL's contribution to City of Hope's nanomedicine research has been invaluable.

"The fact that we can get pristine and really clean nanotubes from Manohara's department is unique," he said. "The fact that we are both collaborating for biological purposes is also really unique."

The collaboration between JPL and City of Hope is conducted under NASA's Innovative Partnership Program, designed to bring benefits of the space program to the public.

Adapted from materials provided by NASA/Jet Propulsion Laboratory.





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Daily Science Journal (Nov. 19, 2007) — People with migraines have differences in an area of the brain that helps process sensory information, including pain, according to a new study.

The study found that part of the cortex area of the brain is thicker in people with migraine than in people who do not have the neurological disorder.

Comparing 24 people with migraine to 12 people without migraine, the study found that the somatosensory cortex area of the brain was an average of 21 percent thicker in those with migraine.

"Repeated migraine attacks may lead to, or be the result of, these structural changes in the brain," said study author Nouchine Hadjikhani, MD, of The Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Boston. "Most of these people had been suffering from migraines since childhood, so the long-term overstimulation of the sensory fields in the cortex could explain these changes. It's also possible that people who develop migraines are naturally more sensitive to stimulation."


Hadjikhani said the results indicate that the brain's sensory mechanisms are important components in migraine. "This may explain why people with migraines often also have other pain disorders such as back pain, jaw pain, and other sensory problems such as allodynia, where the skin becomes so sensitive that even a gentle breeze can be painful."

Other studies have shown changes in the cortex. The area becomes thinner in neurological disorders such as multiple sclerosis and Alzheimer's disease. But the area thickens with extensive motor training and learning.

This research is published in the November 20, 2007, issue of Neurology®, the medical journal of the American Academy of Neurology.

The study was supported by grants from the National Institutes of Health, the Swiss Heart Foundation, and the Harvard School of Dental Medicine Dean's Award.

Adapted from materials provided by American Academy of Neurology, via EurekAlert!, a service of AAAS.

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Scientists Identify Protein That May Promote Migraines

A University of Iowa study may provide an explanation for why some people get migraine headaches while others do not. The researchers found that too much of a small protein called RAMP1 appears to "turn up the volume" of a nerve cell receptor's response to a neuropeptide thought to cause migraines.

The neuropeptide is called CGRP (calcitonin gene-related peptide) and studies have shown that it plays a key role in migraine headaches. In particular, CGRP levels are elevated in the blood during migraine, and drugs that either reduce the levels of CGRP or block its action significantly reduce the pain of migraine headaches. Also, if CGRP is injected into people who are susceptible to migraines, they get a severe headache or a full migraine.

"We have shown that this RAMP protein is a key regulator for the action of CGRP," said Andrew Russo, Ph.D., UI professor of molecular physiology and biophysics. "Our study suggests that people who get migraines may have higher levels of RAMP1 than people who don't get migraines."

RAMP1 is a normal, required subunit of the CGRP receptor. Russo and his colleagues found that overexpression of RAMP1 protein in nerve cells increased the sensitivity and responsiveness of CGRP receptors to the neuropeptide -- more RAMP1 made CGRP receptors react to much lower concentrations of CGRP than usual and caused the receptors to respond more vigorously to the neuropeptide.

The UI team also engineered mice to express human RAMP1 in their nervous system in addition to the normal mouse version of the protein. These mice had double the amount of inflammation in response to CGRP than did normal mice. Nerve-induced inflammation is one of the effects associated with migraine headache.

Russo explained that his study raises the possibility that people who have migraines may have subtle genetic differences in the RAMP1 gene that result in increased levels of RAMP1 protein.

"There is clearly a genetic difference between people who get migraines and those who do not, and we think that difference could be RAMP1. Our studies provide a reason to look for variations in the DNA that encodes RAMP1 in humans," he said.

The study also suggests that the mice engineered to produce elevated levels of RAMP1 protein may be a good model for studying migraine and specifically trying to understand how the neuropeptide, CGRP, is working.

The UI team investigated CGRP receptors in the trigeminal nerve, which is responsible for relaying almost all sensory perception, including pain and touch, for the front of the head. The UI findings reinforce the emerging view that CGRP receptors in the trigeminal nerve play a key role in migraine headache.

However, there are other CGRP receptors throughout the body, and elevated CGRP levels are implicated in other types of pain, including arthritis. Russo predicts that his group's findings about RAMP1 will have implications for pain research beyond migraine headaches.

The study was funded by the National Institutes of Health and published in the Journal of Neuroscience.

Adapted from materials provided by University of Iowa.



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