Tuesday, November 21, 2006

smells like victory

[ Back to EurekAlert! ] Public release date: 21-Nov-2006
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Contact: Josh Chamot
jchamot@nsf.gov
703-292-7730
National Science Foundation

The smell of money

Research suggests an absence of metallic chemicals in the strong metallic odors that result from people handling coins and other metals

It's not hard to recall the pungent scent of a handful of pocket change. Similar smells emanate from a sweat-covered dumbbell or the water emerging from an old metal pipe. Yet no one has been able to identify the exact chemical cause of these familiar odors.

Now, researchers supported by a National Science Foundation (NSF) MUSES award and the UFZ Environmental Research Center in Germany have shown that these odor molecules come not from the penny or the pipes, but from metal-free chemicals erupting into the air when organic substances like sweat interact with the metallic objects.

The researchers--Andrea Dietrich, Dietmar Glindemann, Hans-Joachim Staerk and Peter Kuschk, all from Virginia Tech in Blacksburg--published their findings in the Oct. 20, 2006, Angewandte Chemie International Edition.

"We are the first to demonstrate that when humans describe the 'metallic' odor of iron metal, there are no iron atoms in the odors," said Dietrich. "The odors humans perceive as metallic are really a body odor produced by metals reacting with skin."

Because the makeup of byproduct molecules depends on which organic substances are reacting, the researchers believe the findings could help identify problem odors in potable water or aid doctors searching for disease markers in sweat or other body fluids.

The study, which focused mainly on the reactions of biological fluids with iron, also examined the scents emanating from iron in blood.

"We speculate that the 'blood scent' may result from skin reacting with ferrous iron because the same 'metallic' odor is produced if you rub blood on skin," said Dietrich.

One of the chemicals produced in the reaction is 1-octen-3-one, which has a mushroom-metallic smell and very low odor threshold, meaning that humans can smell it in extremely minute concentrations.

"This may have provided an evolutionary advantage that allowed early humans to track wounded comrades or prey," Dietrich added.

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NSF-PR 06-164

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Sunday, October 15, 2006

Antidepressants linked to 'adolescent' aggression

Antidepressants linked to 'adolescent' aggression

  • 23:00 15 October 2006
  • NewScientist.com news service
  • Roxanne Khamsi

Prozac can make “adolescent” hamsters more aggressive towards their cage-mates, despite the antidepressant drug producing the opposite effect in adult hamsters, making them calmer.

The new findings may help explain why certain antidepressants appear to cause irritability and other abnormal behaviours in teenagers.

Kereshmeh Taravosh-Lahn at the University of Texas at Austin, US, and colleagues gave injections of the drug fluoxetine (sold in pill form as Prozac) to pubescent and mature hamsters. They injected either a low dose (10 milligrams per kilo of body weight) or a high dose (20 milligrams per kilo body weight), while other hamsters received a placebo.

The researchers then introduced a smaller, same-sex hamster into the cage of each experimental hamster and filmed all the fights between the two rodents that were initiated by the subject animals. None of the fights resulted in the skin-breaks or injury to the animals, the researchers stress.

As expected, the pubescent hamsters on a higher dose of drug appeared calmer, initiating about 65% fewer attacks than those on placebo. But surprisingly, those on the lower dose of antidepressant became more aggressive, initiating 40% more fights than those on placebo. Watch a short movie of the aggression in action.

Adult hamsters on either dose of the drug initiated fewer fights than those on placebo.

Binding on

Taravosh-Lahn speculates that different receptors in the brain may be activated by the different dosages in the younger animals. Fluoxetine, like all selective serotonin reuptake inhibitors (SSRIs), works by increasing the amounts of a mood-altering brain chemical called serotonin.

At low doses, serotonin might bind more readily to serotonin-3 receptors, which promote aggression in the hamsters, she says. But at higher doses of antidepressant, the extra serotonin could bind to serotonin-1a receptors, which inhibit aggressive behaviour, she says.

Mature hamsters may have a fewer serotonin-3 receptors in their brains than “adolescent” hamsters, Taravosh-Lahn suggests.

Some young people with depression receive lower doses of antidepressant drugs because of their relatively small weight and size. But Taravosh-Lahn says the findings of the hamster study should prompt a closer look at the effects of this practice.

“We underestimate the differences between the juvenile brain and the adult brain,” says Taravosh-Lahn. “It seems there needs to be more research on the effects of antidepressants on kids.”

Suicidal thoughts

Previous studies have also indicated a link between SSRIs and violent behaviour. Aggression was the most common reason children discontinued taking the drug Zoloft in two clinical trials conducted by pharmaceutical giant Pfizer (PLoS Medicine, DOI: 10.1371/journal.pmed.0030372), for example.

One high-profile case is that of Christopher Pittman, who in 2001 at the age of 12 shot and killed his grandparents before setting their house on fire. Lawyers defending the boy argued the murders were influenced by the antidepressant Zoloft, but a jury disagreed and sentenced him to 30 years in prison in February 2005.

Following a decision by the US Food and Drug Administration in late 2004, all antidepressants in the US now carry strong "black box" warnings, which state that the drugs may cause abnormal behaviours or suicidal thoughts in teenagers.

However, experts stress that antidepressants can dramatically improve the lives of some children. “By in large, children do not become aggressive on Prozac,” says child psychiatrist Stuart Goldman, at the Harvard Medical School in Boston, US.

Journal reference: Behavioral Neuroscience (DOI: 10.1037/0735-7044.120.5.1084)


Thursday, September 21, 2006

The astral plane is thronged with elementals similar to those which enter into the desire body of man, and which also form the simpler desire body of the lower animal. By this department of his nature man comes into immediate relations with these elementals, and by them he forms links with all the objects around him that are either attractive or repulsive to him. By his will, by his emotions, by his desires, he influences these countless beings, which sensitively respond to all the thrills of feeling that he sends out in every direction. His own desire body acts as the apparatus, and just as it combines the vibrations that come from without into feelings, so does it dissociate the feelings that arise within into vibrations.…

We are only concerned with the fact that elementals are addressed by colours, and that colour-words are as intelligible to them as spoken words are to men.The hue of the singing-colour depends on the nature of the motive inspiring the generator of the thought-form. If the motive be pure, loving, beneficent in its character, the colour produced will summon to the thought-form an elemental, which will take on the characteristics impressed on the form by the motive, and act along the line thus traced; this elemental enters into the thought-form, playing to it the part of a soul, and thus an independent entity is made in the astral world, an entity of a beneficent character. If the motive, on the other hand, be impure, revenge­ful, maleficent in its character, the colour produced will summon to the thought-form an elemental which will equally take on the characteristics impressed on the form by the motive and act along the line thus traced; in this case also the elemental enters into the thought-form, playing to it the part of a soul, and thus making an independent entity in the astral world, an entity of a maleficent character. For example, an angry thought will cause a flash of red, the thought-form vibrating so as to produce red; that flash of red is a summons to the elementals and they sweep in the direction of the summoner, and one of them enters into the thought-form, which gives it an inde­pendent activity of a destructive, disintegrating type. Men are continually talking in this colour-language quite unconsciously, and thus calling round them these swarms of elementals, who take up their abodes in the various thought-forms provided; thus it is that a man peoples his current in space with a world of his own, crowded with the offspring of his fancies, desires, impulses and passions. Angels and demons of our own creating throng round us on every side, makers of weal and woe to others, bringers of weal and woe to ourselves—verily, a karmic host.

Clairvoyants can see flashes of colour, constantly changing, in the aura that surrounds every person: each thought, each feeling, thus translating itself in the astral world, visible to the astral sight.. Persons some­what more developed than the ordinary clairvoyant can also see the thought-forms, and can see the effects produced by the flashes of colour among the hordes of elementals.




Wednesday, September 20, 2006

1 in 25 hears voices, no problemo

Voices in the head 'are normal'
Hearing voices in your head is so common that it is normal, psychologists believe.

Dutch findings suggest one in 25 people regularly hears voices.

Contrary to traditional belief, hearing voices is not necessarily a symptom of mental illness, UK researchers at Manchester University say.

Indeed, many who hear voices do not seek help and say the voices have a positive impact on their lives, comforting or inspiring them.

Human diversity

Researcher Aylish Campbell said: "We know that many members of the general population hear voices but have never felt the need to access mental health services.

"Some experts even claim that more people hear voices and don't seek psychiatric help than those who do."

Some who hear voices describe it as being like the experience of hearing someone call your name only to find that there is no one there.


It doesn't seem to be hearing voices in itself that causes the problem
Researcher Aylish Campbell

People also hear voices as if they are thoughts entering the mind from somewhere outside themselves. They will have no idea what the voice might say. It may even engage in conversation.

The Manchester team want to investigate why some people view their voices positively while others become distressed and seek medical help.

Ms Campbell said: "It doesn't seem to be hearing voices in itself that causes the problem.

"What seems to be more important is how people go on to interpret the voices."

She said external factors, such as a person's life experiences and beliefs, might influence this.

Context

"If a person is struggling to overcome a trauma or views themselves as worthless or vulnerable, or other people as aggressive, they may be more likely to interpret their voices as harmful, hostile or powerful.

"Conversely, a person who has had more positive life experiences and formed more healthy beliefs about themselves and other people might develop a more positive view of their voices."

Past studies have found that people who hear voices have often had a traumatic childhood.

Ms Campbell said stigmatisation could also play a role.

"If a person starts hearing voices and also holds the beliefs of some of society that this means they are mentally ill, it is going to cause them more distress. It also stops them talking about it to others."

Professor Marius Romme, president of Intervoice, a "hearing voices" charity, said: "Because of the fears and misunderstandings in society and within psychiatry about hearing voices, they are generally regarded as a symptom of an illness, something that is negative to be got rid of, and consequently the content and meaning of the voice experience is rarely discussed.

"Our work and research has shown more than 70% of people who hear voices can point to a traumatic life event that triggered their voices; that talking about voices and what they mean is a very effective way to reduce anxiety and isolation; and that even when the voices are overwhelming and seemingly destructive they often have an important message for the hearer."

Paul Corry of the mental health charity Rethink said: "Rethink welcomes this investigation, which we hope will help support our campaign to bring mental health issues into the mainstream."

People interested in participating in the University of Manchester research should call 0161 306 0405 or email voiceresearch@hotmail.co.uk.

Participants should be aged 16 or over, have been hearing voices for at least six months and live in the northwest of England.

Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/5346930.stm

Published: 2006/09/18 00:39:17 GMT

© BBC MMVI


Thursday, September 14, 2006

fine-tuning the brainwaves

Slow brain waves play key role in coordinating complex activity

– While it is widely accepted that the output of nerve cells carries information between regions of the brain, it's a big mystery how widely separated regions of the cortex involving billions of cells are linked together to coordinate complex activity.

A new study by neuroscientists at the University of California, Berkeley, and neurosurgeons and neurologists at UC San Francisco (UCSF) is beginning to answer that question.

electrode grids on brain lobes
UCSF neurosurgeons place 64-electrode grids on the surface of the brain's temporal and frontal lobes to locate regions where epileptic seizures originate. These grids allowed UC Berkeley neuroscientists to study the interaction of brain waves during simple tasks, such as word recognition or hand movements. (Images courtesy the Knight Lab)

"One of the most important questions in neuroscience is: How do areas of the brain communicate?" said Dr. Robert Knight, professor of psychology, Evan Rauch Professor of Neuroscience and director of the Helen Wills Neuroscience Institute at UC Berkeley. "A simple activity like responding to a question involves areas all over the brain that hear the sound, analyze it, extract the relevant information, formulate a response, and then coordinate your lips and mouth to speak. We have no idea how information moves between these areas."

By measuring electrical activity in the brains of pre-surgical epilepsy patients, the researchers have found the first evidence that slow brain oscillations, or theta waves, "tune in" the fast brain oscillations called high-gamma waves that signal the transmission of information between different areas of the brain. In this way, the researchers argue, areas like the auditory cortex and frontal cortex, separated by several inches in the cerebral cortex, can coordinate activity.

"If you are reading something, language areas oscillate in theta frequency allowing high-gamma-related neural activity in individual neurons to transmit information," said Knight. "When you stop reading and begin to type, theta rhythms oscillate in motor structures, allowing you to plan and execute your motor response by way of high gamma. Simple, but effective."

The findings are reported in the Sept. 15 issue of Science.

Tuning in high-frequency brain waves

The researchers found that when people are asked to do a simple task, such as listening to a list of words, the slow, theta oscillations in the hearing area of the brain become coupled with the fast, high-gamma oscillations in the same area. When two different brain areas then oscillate together at the same theta frequency and phase, it becomes much easier for these regions to tune in the high-gamma oscillations that transfer information between them.

Diagrams comparing high-gamma activity in the brain in response to different sounds
Electrodes on the brain surface detect high-gamma activity (star) in only one area when the patient hears a tone (top), while more areas exhibit high-gamma activity in response to a recognizable phoneme (middle) or word (bottom). Theta waves in these active areas lock onto the same frequency and phase, tuning in high-frequency signals tranferring information.

"One theory about how the brain is organized says that there is a hierarchy of oscillations that can control how one neuron talks to another neuron, or how one brain area talks to another brain area," said lead author Ryan Canolty, a UC Berkeley graduate student in the Helen Wills Neuroscience Institute. "Our study was designed to test the idea that the high-frequency oscillations generated by the brain are coupled to the slower theta oscillations.

"This coupling is important because the two rhythms have different functions and operate on different spatial scales - a patch of high frequency activity is very localized, about the size of a dime or smaller on the brain, and is associated with bottom-up sensory or motor processing, while the theta rhythm is much more spatially widespread, the size of a silver dollar or larger on the surface of the cortex, and is tied to top-down executive processes like attention and memory. Coupling between these two rhythms could be what gives the brain a way to connect low-level perceptions and actions to high-level goals and intentions."

Brain waves - such as the slow alpha waves of the relaxed or idling brain or the fast, seemingly random pulses accompanying dream sleep - are generated by coordinated firing of neurons in the brain triggered by waves of excitability that wash over an area. Waves of excitability in the theta range of oscillations lower the threshold for neuron firing, making it more likely that input arriving at the critical time will make neurons in that area of the brain fire.

Typically measured with electrodes on the scalp (electroencelphalograms, or EEGs), brain waves are classified from the very slowest delta waves (1-3 oscillations per second) seen in very deep sleep, through theta (4-7 oscillations per second), alpha (8-13 oscillations per second) and beta (14-30 oscillations per second) to the most rapid firings in the human brain - gamma oscillations (30-60 oscillations per second). Because slow firings are detected when the brain is least active, while rapid firings accompany activity, neuroscientists think that information in the brain is carried by the high frequencies.

Until recently, scalp recordings could detect gamma waves only up to 70 firings per second, but in 1998 researchers at Johns Hopkins University discovered brain waves up to 100 oscillations per second by placing electrodes directly on the surface of the brain. Knight and his UC Berkeley group used the same technique to show last year that brain oscillations can occur up to 200 times per second - and perhaps as fast as 300 times per second. Waves with 80-200 oscillations per second are called high-gamma, though they likely play an entirely different role from the traditional lower frequency gamma waves, Knight said.

One theory is that brain oscillations organize neurons into cooperating groups: low-frequency waves synchronize the firing of large groups of neurons, while the higher frequencies synchronize smaller groups. Though neuroscientists don't know what underlying neural activity generates the waves recorded on the surface of the cortex, the oscillations may be generated spontaneously by neurons when grouped together in the hundreds of thousands.

"When you have to remember a new phone number or attend to moving cars as you cross an intersection, you'll have an increase in the strength of the theta rhythm in many different brain regions," Canolty said. "The idea is that this theta rhythm might be more of an executive control mechanism to tie different brain areas together, whereas high-gamma waves within a region tie groups of cells together and time when their output can be sent or when input from another area can be received."

Recording brain waves in epilepsy patients

To test these hypotheses, Knight and his colleagues teamed up with UCSF doctors Nick Barbaro, neurosurgeon, professor of neurosurgery and director of surgical epilepsy; Mitchel Berger, neurosurgeon, professor and chair of neurosurgery and director of the Brain Tumor Research Center; and Heidi Kirsch, epileptologist, assistant professor in residence of neurology, to record brain activity in brain tumor and epilepsy patients scheduled for surgery to remove a portion of their brains. The epilepsy patients typically have brain activity measured up to a week beforehand so that surgeons can localize important areas they need to avoid, such as centers of language, vision or motor activity.

The goal of the UC Berkeley-UCSF Intracranial Project is to use high-gamma waves to produce a finer map of the brain to guide neurosurgeons during brain surgery and potentially to use these same high frequency oscillations to control robotic devices in paralyzed patients.

"This represents a paradigm shift in how we map brain function," said Berger. "As a neurosurgeon, I work within these very complicated cortical and subcortical areas where regions talk to each other, and there is a level of connectivity between cortical regions not apparent by any current means of detection.

"By measuring high-gamma band activity, we will be able to see in real time, during surgery, how cortical regions are connected through subcortical systems, allowing us to understand how these regions process information. This hold the key to understanding diseases like autism, which clearly involves the subcortical pathways."

In these clinical procedures, Barbaro removed a portion of each patient's skull and placed a grid of 64 electrodes on the surface of the brain's frontal and temporal lobes to precisely localize the source of the seizure so it could be removed in a subsequent surgical procedure. Knight, Canolty and their UC Berkeley colleagues then recorded activity in response to sounds and visual stimulation.

Several hours of data from five different patients revealed that high-gamma activity was locked to the theta rhythm in many different areas of the brain. The stronger the theta wave, the stronger the coupling to high-gamma oscillations.

The pattern of coupling between theta and high-gamma also changed with the task. Patients listening to a list of words would show strong coupling in a particular set of brain regions, but when they then had to name pictures, a different set of brain areas would show strong coupling.

"We used to think that one little patch of cortex takes care of this function and another little patch takes care of that function, but now we see it's more about systems that are cooperating on one task, then they switch over and cooperate on another task," said UCSF's Kirsch. "On the fly you want to link these areas to do a task, and when the task is over, you want to decouple them and let them link up with someone else. Ryan has shown that the theta waves allow this coupling and uncoupling by locking into phase."

Knight and his colleagues continue to probe the connection between waves of different frequency in the brain and are building a more closely spaced grid of electrodes that can measure finer detail on the brain's surface. They also plan to combine brain grid recordings with recordings from individual neurons in the cortex to find out what really generates the brain waves that EEGs and ECoGs measure.

Coauthors of the Science paper include UC Berkeley graduate students Erik Edwards and Maryam Soltani of the psychology department and S. S. Dalal of the bioengineering department; and radiologist Sri S. Nagarajan of UC Berkeley's Department of Bioengineering and UCSF's Department of Radiology.

The work was supported by the Rauch family and by the National Institute of Neurological Disorders and Stroke and the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health.


Monday, September 04, 2006

how some brains defend against alcoholism

Public release date: 4-Sep-2006

Contact: Dennis Tartaglia
dennist@mbooth.com
212-481-7000
DOE/Brookhaven National Laboratory

Study offers clues to brain's protective mechanisms against alcoholism
A new study provides clues that differing brain chemistry may provide part of the answer to why some people with a strong family history of alcoholism develop alcohol dependency while others do not


UPTON, NY - Why do some people with a strong family history of alcoholism develop alcohol dependency while others do not? A new study provides clues that differing brain chemistry may provide part of the answer. Researchers from four scientific institutions and federal agencies working at the U.S. Department of Energy's Brookhaven National Laboratory have found that elevated levels of D2 receptors for dopamine -- a chemical "messenger" in the brain's reward circuits -- may provide a protective effect for those most at risk for developing alcoholism. The study, part of an ongoing effort to understand the biochemical basis of alcohol abuse, also provides new evidence for a linkage between emotional attributes and brain function. The study appears in the September 2006 issue of the Archives of General Psychiatry.

"Higher levels of dopamine D2 receptors may provide protection against alcoholism by triggering the brain circuits involved in inhibiting behavioral responses to the presence of alcohol," said lead author Nora D. Volkow, Director of the National Institute on Drug Abuse (NIDA) and former Associate Laboratory Director for life sciences research at Brookhaven Lab. "This means that treatment strategies for alcoholism that increase dopamine D2 receptors could be beneficial for at-risk individuals."

Earlier Brookhaven Lab studies have demonstrated that increasing dopamine D2 receptors by genetic manipulation decreased alcohol consumption in rats that had been trained (http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr090501.htm) or that were genetically predisposed (http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=04-47) to drink large quantities of alcohol. Another study found that such D2-receptor "gene therapy" reduced drinking in mice with normal to moderately low levels of D2 receptors (http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=05-49). The current study adds to the evidence that D2 receptors modulate the motivation to drink alcohol and that increasing these receptors could play a role in the treatment of alcoholism. The D2 receptor is one of five dopamine receptor subtypes.

In this study, researchers compared the number of dopamine D2 receptors in two groups: 16 nonalcoholic individuals with no family history of alcoholism and 15 nonalcoholic individuals who had a positive family history of alcoholism -- an alcoholic biological father with early onset of alcoholism and at least two other first or second degree relatives (parent, child, sibling, grandparent, grandchild, cousin, aunt, uncle) with alcoholism. The latter group was at a very high risk of developing alcoholism. The researchers studied high-risk individuals rather than looking at people with drinking disorders because chronic alcohol abuse reduces the number of dopamine receptors, making comparisons difficult. Participants were scanned with positron emission tomography (PET) and were given two radioactive tracers to assess their dopamine D2 receptor levels and brain glucose -- a marker of brain function.

The scans demonstrated high levels of dopamine D2 receptors in the brains of participants with a family history of alcoholism, particularly in their frontal regions -- 10 percent higher, on average, than in the brains of those with no family history. These areas of the brain -- including the caudate and ventral striatum -- are involved in emotional reactions to stress and cognitive control of decisions about drinking.

"This suggests that dopamine D2 receptors in these brain regions protect high-risk individuals from becoming alcoholic," said principal investigator Gene-Jack Wang, who chairs Brookhaven Lab's Medical Department and is clinical head of the PET Imaging Group at the Lab's Center for Translational Neuroimaging. "This protective effect may combine with emotional and environmental factors to compensate for higher inherited vulnerability."

Each study participant was given a Multidimensional Personality Questionnaire, to measure for extroversion and introversion, also known as positive and negative emotionality. Positive emotionality is believed to decrease the likelihood of alcohol abuse. This test was given to determine whether the receptors' protective effect was associated with this or other personality characteristics.

"We found that individuals who had the highest level of dopamine D2 receptors were those who were extroverted and more motivated by positive rewards," said Volkow. "This held true for both individuals with and without a family history of alcoholism."

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This study was funded by the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science and by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Study coauthors include Henri Begleiter and Bernice Porjesz, SUNY Downstate Medical Center; and Joanna Fowler, Christopher Wong, Jean Logan, Rita Goldstein, David Axeloff, Peter Thanos, Yeming Ma, and Frank Telang at Brookhaven Lab (with Thanos, Ma and Telang working under the auspices of NIAAA's Intramural Research Program).

DOE has a long-standing interest in research on addiction that builds, as this study does, on the knowledge of brain receptors gained through brain-imaging studies. Brain-imaging techniques such as MRI and PET are a direct outgrowth of DOE's support of basic physics and chemistry research.

Note to local editors: Gene-Jack Wang lives in Port Jefferson, New York.

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.

Visit Brookhaven Lab's electronic newsroom for links, news archives, graphics, and more: http://www.bnl.gov/newsroom


Wednesday, July 19, 2006

but will it work on the chronic pain of daily life

Public release date: 19-Jul-2006

Contact: Craig LeMoult
cel2113@columbia.edu
212-305-0820
Columbia University Medical Center

Columbia University researchers discover on-off switch for chronic pain

New York, NY, July 19, 2006 -- Chronic pain affects approximately 48 million people in the U.S. and current medications are either largely ineffective or have serious side effects. But researchers from Columbia University Medical Center have discovered a protein in nerve cells that acts as a switch for chronic pain, and have applied for a patent to develop a new class of drugs that will block chronic pain by turning this switch off. The discovery is published on the website of the journal Neuroscience, and will appear in the publication's August issue.

Most prior attempts at alleviating chronic pain have focused on the "second order" neurons in the spinal cord that relay pain messages to the brain. It's difficult to inhibit the activity of these neurons with drugs, though, because the drugs need to overcome the blood-brain barrier. Instead, the CUMC researchers have focused on the more accessible "first order" neurons in the periphery of our body that send messages to the spinal cord.

Pain becomes chronic when the activity of first and second order neurons persists after damaged neuron heals or the tissue inflammation subsides. It's been known for years that for chronic pain to persist, a master switch must be turned on inside the peripheral neurons, though until now the identity of this switch remained a mystery. Richard Ambron, Ph.D., professor of cell biology, and Ying-Ju Sung, Ph.D., assistant professor, both in the department of Anatomy and Cell Biology, have now discovered that the switch is an enzyme called protein kinase G (PKG).

"We're very optimistic that this discovery and our continued research will ultimately lead to a novel approach to pain relief for the millions suffering from chronic pain," said Dr. Ambron.

The researchers found that upon injury or inflammation, the PKG is turned on and activated. Once activated, these molecules set off other processes that generate the pain messages. As long as the PKG remains on, the pain persists. Conversely, turning the PKG off relieves the pain, making PKG an excellent target for therapy.

Dr. Ambron and Dr. Sung have applied for a patent for the pathway that turns on the PKG, as well as several molecules that inhibit it.

Based on the 2004 Americans Living with Pain Survey, 72 percent of people with chronic pain have lived with it for more than three years, including a third who have lived with pain for more than a decade. Yet nearly half of people with pain do not consult a physician for several months or longer, despite the impact the pain has on their lives.

The worldwide painkiller market was worth $50 billion in 2005 and is expected to increase to $75 billion by 2010 and $105 billion by 2015. But none of the existing drugs on the market are adequate to deal with chronic pain. Cox-2 inhibitors carry severe risk of side effects, opioids are highly addictive, Tylenol is ineffective for chronic pain, and other pain drugs cause significant drowsiness.

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