NEWLY DISCOVERED BRAIN CELLS EXPLAIN A PROSOCIAL EFFECT OF OXYTOCIN

Oxytocin, the body's natural love potion, helps couples fall in love, makes mothers bond with their babies, and encourages teams to work together. Now new research at Rockefeller University reveals a mechanism by which this prosocial hormone has its effect on interactions between the sexes, at least in certain situations. The key, it turns out, is a newly discovered class of brain cells.

"By identifying a new population of neurons activated by oxytocin, we have uncovered one way this chemical signal influences interactions between male and female mice," says Nathaniel Heintz, James and Marilyn Simons Professor and head of the Laboratory of Molecular Biology.

The findings, published today in Cell (October 9), had their beginnings in a search for a new type of interneuron, a specialized neuron that relays messages to other neurons across relatively short distances. As part of her doctoral thesis, Miho Nakajima began creating profiles of the genes expressed in interneurons using a technique known as translating ribosome affinity purification (TRAP) previously developed by the Heintz lab and Paul Greengard's Laboratory of Molecular and Cellular Neuroscience at Rockefeller. Within some profiles from the outer layer of the brain known as the cortex, she saw an intriguing protein: a receptor that responds to oxytocin.

"This raised the question: What is this small, scattered population of interneurons doing in response to this important signal, oxytocin?" Nakajima says. "Because oxytocin is most involved in social behaviors of females, we decided to focus our experiments on females."

To determine how these neurons, dubbed oxytocin receptor interneurons or OxtrINs, affected behavior when activated by oxytocin, she silenced only this class of interneurons and, in separate experiments, blocked the receptor's ability to detect oxytocin in some females. She then gave them a commonly used social behavior test: Given the choice between exploring a room with a male mouse or a room with an inanimate object -- in this case a plastic Lego block -- what would they do? Generally, a female mouse will go for the non-stackable choice. Legos just aren't that interesting to rodents. But Nakajima's results were confusing: Sometimes the mice with the silenced OxtrINs showed an abnormally high interest in the Lego, and sometimes they responded normally.

This led her to suspect the influence of the female reproductive cycle. In another round of experiments, she recorded whether the female mice were in estrus, the sexually receptive phase, or diestrus, a period of sexual inactivity. Estrus, it turned out, was key. Female mice in this phase showed an unusual lack of interest in the males when their receptors were inactivated. They mostly just sniffed at the Lego. There was no effect on mice is diestrus, and there was no effect if the male love interest was replaced with a female. When Nakajima tried the same alteration in males, there was also no effect.

"In general, OxtrINs appear to sit silently when not exposed to oxytocin," says Andreas Görlich, a postdoc in the lab who recorded the electrical activity of these neurons with and without the hormone. "The interesting part is that when exposed to oxytocin these neurons fire more frequently in female mice than they do in male mice, possibly reflecting the differences that showed up in the behavioral tests."

"We don't yet understand how, but we think oxytocin prompts mice in estrus to become interested in investigating their potential mates," Nakajima says. "This suggests that the social computation going on in a female mouse's brain differs depending on the stage of her reproductive cycle."

Oxytocin has similar effects for humans as for mice, however, it is not yet clear if the hormone influences the human version of this mouse interaction, or if it works through a similar population of interneurons. The results do, however, help explain how humans, mice and other mammals respond to changing social situations, Heintz says.

"Oxytocin responses have been studied in many parts of the brain, and it is clear that it, or other hormones like it, can impact behavior in different ways, in different contexts and in response to different physiological cues," he says. "In a general sense, this new research helps explain why social behavior depends on context as well as physiology."

Why Neuropathy Means Your Brain Cant Avoid Falls

Today's post from sciencedaily.com (see link below) is an interesting one for many people living with neuropathy, irrespective of their age. If you have nerve damage problems in your feet and legs, balance becomes an issue, not only with normal walking but also if you happen to trip and fall. The article suggests that the younger you are, the better your chances of recovering from the stumble and avoiding a bone-breaking fall but the older you are increases the risk of a serious injury from loss of balance. The science shows that it has to do with the brain's reaction times to threatening situations. When you're young, your brain identifies the risk and takes measures to avoid it and correct your stance before you fall, whereas older people have slower reaction times and often can't correct the situation in time. What isn't completely clear is if the nerve damage has anything to do with the 'slowing down' of the brain's reactions, or whether, like with other bodily functions, age simply means a reduction of all optimal functioning. Whatever the exact reasons are, the facts are obvious:- the older we are, the more likely we are to fall and break something after a neuropathy induced stumble. Can we do anything about it? Well, neuropathy patients are well-practiced in training their brain to concentrate at all times when walking but occasionally, the wrong signals the brain is receiving mean that an accident is almost inevitable. Whatever our age, with nerve damage you always have to be as alert as humanly possible. Lack of feeling, numbness, foot pain, burning and tingling and critically, misinterpreting signals we've grown up getting used to, make life with neuropathy a bit of a lottery. Avoiding broken bones is a daily objective for neuropathy sufferers and I don't think you have to be elderly to be aware of that!

For geriatric falls, 'brain speed' may matter more than lower limb strength 
Date:December 21, 2016Source:University of Michigan Health System 

Summary: It's not only risk factors like lower limb strength and precise perception of the limb's position that determine if a geriatric patient will recover from a perturbation, but also complex and simple reaction times, say researchers.

"Why does a 30-year-old hit their foot against the curb in the parking lot and take a half step and recover, whereas a 71-year-old falls and an 82-year-old falls awkwardly and fractures their hip?" asks James Richardson, M.D., professor of physical medicine and rehabilitation at the University of Michigan Comprehensive Musculoskeletal Center.

For the last several years, Richardson and his team set out to answer these questions, attempting to find which specific factors determine whether, and why, an older person successfully recovers from a trip or stumble. All this in an effort to help prevent the serious injuries, disability, and even death, that too often follow accidental falls.

"Falls research has been sort of stuck, with investigators re-massaging over 100 identified fall 'risk factors,' many of which are repetitive and circular," Richardson explains. "For example, a 2014 review lists the following three leading risk factors for falls: poor gait/balance, taking a large number of prescription medications and having a history of a fall in the prior year."

Richardson continues, "If engineers were asked why a specific class of boat sank frequently and the answer came back: poor flotation and navigational ability, history of sinking in the prior year and the captain took drugs, we would fire the engineers! Our goal has been to develop an understanding of the specific, discrete characteristics that are responsible for success after a trip or stumble while walking, and to make those characteristics measurable in the clinic."

Richardson's latest research finds that it's not only risk factors like lower limb strength and precise perception of the limb's position that determine if a geriatric patient will recover from a perturbation, but also complex and simple reaction times, or as he prefers to refer to it, a person's "brain speed." The work is published in the January 2017 edition of the American Journal of Physical Medicine & Rehabilitation.

"Our study wanted to identify relationships between complex and simple clinical measures of reaction time and indicators of balance in elderly subjects with diabetic peripheral neuropathy, nerve damage that can occur in those with diabetes," Richardson says.

"These patients fall twice as often as people their age typically do, so we wanted to examine each person's ability to make a decision in less than half a second, or around 400 milliseconds. Importantly, this is also about the length of time the foot is in the air before landing while walking, and about the time available to recover from a stumble or trip."

He realized they needed a new, easy way to measure that rapid decision-making ability.

Measuring simple and complex reaction time

Using a device developed with U-M co-inventors James T. Eckner, Hogene Kim and James A. Ashton-Miller, simple reaction time is measured much like a drop-ruler test used in many school science classes, but is a bit more standardized.

"The clinical reaction time assessment device consists of a long, lightweight stick attached to a rectangular box at one end. The box serves as a finger spacer to standardize initial hand position and finger closure distance, as well as a housing for the electronic components of the device," Richardson says.

To measure simple reaction time, the patient or subject sits with the forearm resting on a desk with the hand off the edge of the surface. The examiner stands and suspends the device with the box hanging between the subject's thumb and other fingers and lets the device drop at varying intervals. The subject catches it as quickly as possible and the device provides a display of the elapsed time between drop and catch, which serves as a measurement of simple reaction time.

Although measuring simple reaction time is useful, Richardson says that the complex reaction time accuracy has been more revealing. The initial set up of the device and subject is the same. However, in this instance, the subject's task is to catch the falling device only during the random 50 percent of trials where lights attached to the box illuminate at the moment the device is dropped, and to resist catching it when the lights do not illuminate.

"Resisting catching when the lights don't go off is the hard part," Richardson says. "We all want to catch something that is falling. The subject must perceive light illumination status and then act very quickly to withhold the natural tendency to catch a falling object."

In the study, Richardson and team used the device with a sample of 42 subjects, 26 with diabetic neuropathy and 16 without, with an average age of 69.1 years old, to examine their complex reaction time accuracy and their simple reaction time latency, in addition to the usual measures of leg strength and perception of motion.

They then looked to see how well these measures predicted one-legged balance time, the ability to control step width when walking on a hazardous uneven surface in the research lab and major fall-related injuries over the next 12 months.

Examining the results

In the subjects with diabetic peripheral neuropathy, good complex reaction time accuracy and quick simple reaction time were strongly associated with a longer one-legged balance time, and were the only predictors of good control of step width on the uneven surface. In addition, they appeared to identify those who sustained major fall-related injury during the one-year follow up. Surprisingly, the measures of leg strength and motion perception had no influence on step width control on the hazardous surface and did not appear to predict major injury.

"Essentially we found that those who were able to grab the device quickly, or quickly make the decision to let it drop, had quick brains that were somehow helping them stay balanced and avoid aberrant steps on the uneven surface," Richardson says.

He explains that the ability to avoid aberrant steps after hitting a bump while walking, and stay balanced while performing the trials, were likely based on the participant's brain processing speed. In particular, the ability to quickly withhold, or inhibit, a planned movement is required for good complex reaction accuracy and responding to a perturbation while walking. In both cases, the original plan of action must be aborted and a new one substituted within approximately a 400 milliseconds time interval.

"With this in mind, it makes perfect sense that brains fast enough to have good complex reaction time accuracy were also fast enough to quickly pay attention to the perturbation while walking, inhibit the step that was planned and quickly execute a safer alternative," Richardson says. "The faster your brain can oscillate between various external stimuli, or events, and your own internal thinking clutter, the better off you are. When an elderly person falls, it seems likely that their brain is not keeping up with what is happening and so it is not able to quickly, and selectively, attend to a particular stimulus, such as hitting a curb."

Richardson says this assessment, which cannot be produced from a computer or pen/pencil tests, could be valuable to other health care providers, such as primary care physicians, neurologists, geriatricians and a variety of rehabilitation professionals.

Story Source:

Materials provided by University of Michigan Health System. Note: Content may be edited for style and length.

Journal Reference:
James K. Richardson, James T. Eckner, Lara Allet, Hogene Kim, James A. Ashton-Miller. Complex and Simple Clinical Reaction Times Are Associated with Gait, Balance, and Major Fall Injury in Older Subjects with Diabetic Peripheral Neuropathy. American Journal of Physical Medicine & Rehabilitation, 2017; 96 (1): 8 DOI: 10.1097/PHM.0000000000000604

https://www.sciencedaily.com/releases/2016/12/161221090359.htm

BRAIN DIFFERENCE SOMETIMES ADOLESCENTS JUST CANT RESIST

Don't get mad the next time you catch your teenager texting when he promised to be studying. He simply may not be able to resist

A University of Iowa study found teenagers are far more sensitive than adults to the immediate effect or reward of their behaviors. The findings may help explain, for example, why the initial rush of texting may be more enticing for adolescents than the long-term payoff of studying.

"The rewards have a strong, perceptional draw and are more enticing to the teenager," says Jatin Vaidya, a professor of psychiatry at the UI and corresponding author of the study, which appeared online this week in the journal Psychological Science. "Even when a behavior is no longer in a teenager's best interest to continue, they will because the effect of the reward is still there and lasts much longer in adolescents than in adults."

For parents, that means limiting distractions so teenagers can make better choices. Take the homework and social media dilemma: At 9 p.m., shut off everything except a computer that has no access to Facebook or Twitter, the researchers advise.

"I'm not saying they shouldn't be allowed access to technology," Vaidya says. "But they need help in regulating their attention so they can develop those impulse-control skills."

In their study, "Value-Driven Attentional Capture in Adolescence," Vaidya and co-authors Shaun Vecera, a professor of psychology, and Zachary Roper, a graduate student in psychology, note researchers generally believe teenagers are impulsive, make bad decisions, and engage in risky behavior because the frontal lobes of their brains are not fully developed.

But the UI researchers wondered whether something more fundamental was going on with adolescents to trigger behaviors independent of higher-level reasoning.

"We wanted to try to understand the brain's reward system and how it changes from childhood to adulthood," says Vaidya, who adds the reward trait in the human brain is much more primitive than decision-making. "We've been trying to understand the reward process in adolescence and whether there is more to adolescent behavior than an under-developed frontal lobe," he adds.

For their study, the researchers recruited 40 adolescents, ages 13 and 16, and 40 adults, ages 20 and 35. First, participants were asked to find a red or green ring hidden within an array of rings on a computer screen.

Once identified, they reported whether the white line inside the ring was vertical or horizontal. If they were right, they received a reward between 2 and 10 cents, depending on the color. For some participants, the red ring paid the highest reward; for others, it was the green. None was told which color would pay the most.

After 240 trials, the participants were asked whether they noticed anything about the colors. Most made no association between a color and reward, which researchers say proves the ring exercise didn't involve high-level, decision-making.

In the next stage, participants showed they had developed an intuitive association when they were asked to find a diamond-shaped target. This time, the red and green rings were used as decoys.

At first, the adolescents and adults selected the color ring that garnered them the highest monetary reward, the goal of the first trial. But in short order, the adults adjusted and selected the diamond. The adolescents did not.

Even after 240 trials, the adolescents were still more apt to pick the colored rings.

"Even though you've told them, 'You have a new target,' the adolescents can't get rid of the association they learned before," Vecera says. "It's as if that association is much more potent for the adolescent than for the adult.

"If you give the adolescent a reward, it will persist longer," he adds. "The fact that the reward is gone doesn't matter. They will act as if the reward is still there."

Researchers say that inability to readily adjust behavior explains why, for example, a teenager may continue to make inappropriate comments in class long after friends stopped laughing.

In the future, researchers hope to delve into the psychological and neurological aspects of their results.

"Are there certain brain regions or circuits that continue to develop from adolescence to adulthood that play role in directing attention away from reward stimuli that are not task relevant?" Vaidya asks. "Also, what sort of life experiences and skill help to improve performance on this task?"

The study was funded by the University of Iowa's Social Sciences Funding Program.

Protein Essential For Brain Muscle Coordination

Today's post from sciencedaily.com (see link below) talks about the relationship between the brain and muscle function and how a certain protein needs to be present on the surface of both in order to function properly. Many people with neuropathy eventually have problems with muscular weakness; almost as if the muscles refuse to co-operate with what the brain tells them to do. This article, despite being of a complex scientific nature, may give you an idea of why this may happen. It's sometimes difficult to understand what happens at a cellular or molecular level in our bodies but just being aware that there are very complex operations at work, helps broaden our understanding of our neuropathy.

Strong Communication Between Brain and Muscle Requires Both Having the Protein LRP4

ScienceDaily (July 11, 2012)

Communication between the brain and muscle must be strong for us to eat, breathe or walk. Now scientists have found that a protein known to be on the surface of muscle cells must be present in both tissues to ensure the conversation is robust.

Scientists at the Medical College of Georgia at Georgia Health Sciences University have shown that without LRP4 in muscle cells and neurons, communication between the two cells types is inefficient and short-lived.

Problems with the protein appear to contribute to disabling disorders such as myasthenia gravis and other forms of muscular dystrophy. The MCG scientists reported finding antibodies to LRP4 in the blood of about 2 percent of patients with muscle-degenerating myasthenia gravis in Archives of Neurology earlier this year.

Scientists know that LRP4 plays an important role in the muscle cell, where it receives cues from the brain cell that it's time to form the receptors that will be enable ongoing communication between the two, said Dr. Lin Mei, Director of the GHSU Institute of Molecular Medicine and Genetics and corresponding author of the study in the journal Neuron.

However when Dr. Haitao Wu deleted LRP4 just from muscle cells, a connection -- albeit a weak one -- still formed between muscle and brain cells. The mice survived several days during which they experienced some of the same muscle weakness as patients with myasthenia gravis. "That's against the dogma," Mei said. "If LRP4 is essential only in the muscle cells, how could the mice survive?" When they totally eliminated LRP4, neuromuscular junctions never formed and the mice didn't survive.

Additional evidence suggests that LRP4 in the neurons is vital, said Wu, postdoctoral fellow and the study's first author. "When we knocked out the LRP4 gene in the muscles, there was some redundant function coming from the motor neuron, like a rescue attempt," he said. They documented the neuron reaching out to share LRP4 with the muscle cell. Unfortunately, the gesture was not sufficient.

"The nerve does not get the stop signal," Mei said, referencing images of too-long neurons that never got the message from the muscle that they have gone far enough. When they cut the elongated nerves, they found they didn't contain enough vesicles, little packages of chemical messengers that are the hallmark of brain cell communication. On the receiving end, muscle cells developed receptors that were too small and too few -- hence, the tenuous communication network. "When LRP4 in the muscle is taken out, not surprisingly, the muscle has some kind of a problem," Mei said. "What was very surprising was that the motor neurons also have problems."

"The talk between motor neurons and muscle cells is very critical to the synapse formation and the very precise action between the two," Wu said. Mei's lab earlier established that the conversation goes both ways.

The scientists believe about 60 percent of the LRP4 comes from muscle cells, about 20 percent from brain cells -- which helps explain why the brain's effort to share is insufficient -- and the remainder from cells in spaces between the two. In addition to better explaining nerve-muscle communication, the scientists hope their findings will eventually enable gene therapy that delivers LRP4 to bolster insufficient levels in patients.

Other early and key players in establishing nerve-muscle conversation include agrin, a protein that motor neurons release to direct construction of the synapse, a sort of telephone line between the nerve and muscle. MuSK on the muscle cell surface initiates critical internal cell talk so synapses can form and receptors that enable specific commands will cluster at just the right spot.

Mei's lab reported in Neuron in 2008 that agrin starts talking with LRP4 on the muscle cell surface, then recruits the enzyme MuSK to join the conversation. LRP4 and MuSK become major components of the receptor needed for the muscle cell to receive the message agrin is sending.
The agrin-MuSK signaling pathway has been implicated in muscular dystrophy, a group of genetic diseases that lead to loss of muscle control because of problems with neurons, muscle cells and/or their communication. Some reports have implicated a mutant MuSK as a cause of muscular dystrophy and autoantibodies (antibodies the body makes against itself) to MuSK have been found in the blood of some patients.

http://www.sciencedaily.com/releases/2012/07/120711123003.htm

Brain abscess

 Brain abscess (or cerebral abscess) is definitely an abscess caused by inflammation and assortment of infected material, originating from local (ear infection, dental abscess, infection of paranasal sinuses, infection from the mastoid air cells from the temporal bone,epidural abscess) or remote (lung, heart, kidney etc.) infectious sources, inside the brain tissue. The problem may also be introduced via a skull fracture carrying out a head trauma or surgical treatments. Brain abscess is usually associated withcongenital cardiovascular disease in young children. It might occur at all ages but is most typical in the third decade of life.
Deadly brain abscesses because of infection caused from tongue piercings have occurred


Clinical features
The the signs of brain abscess are caused by a mix of increased intracranial pressure as a result of space-occupying lesion (headache, vomiting, confusion, coma), infection (fever, fatigue etc.) and focal neurologic brain injury (hemiparesis,aphasia etc.). The most frequent presenting symptoms are headache, drowsiness, confusion, seizures, hemiparesis or speech difficulties along with fever with a rapidly progressive course. The symptoms and findings depend largely around the specific location from the abscess in the brain. An abscess within the cerebellum, for instance, may cause additional complaints due to brain stem compression and hydrocephalus. Neurological examination may reveal a stiff neck in occasional cases (erroneously suggesting meningitis). The famous triad of fever, headache and focal neurologic findings are highly suggestive of brain abscess.

Causes, incidence, and risks
Brain abscesses commonly occur when bacteria or fungi infect area of the brain. Swelling and irritation (inflammation) develop in reaction to this infection. Infected cognitive abilities, white blood cells, live and dead bacteria, and fungi collect within an area of the brain. Tissue forms for this area and creates full of.
While this immune response can safeguard the brain by isolating the problem, it can also do more damage than good. The brain swells. Since the skull cannot expand, the mass may put pressure on delicate brain tissue. Infected material can block the arteries of the brain.
The germs that create a brain abscess usually get to the brain through the blood. The origin of the infection is usually not found. However, the most typical source is a lung infection. More infrequently, a heart infection would be to blame. Germs could also travel from a nearby infected area (for instance, an ear infection or perhaps a tooth abcess) or go into the body during an injury (like a gun or knife wound) or surgery.
In youngsters with heart disease or perhaps a birth defect, for example those with tetralogy of fallot, infections tend to be more able to reach the brain in the intestines, teeth, or any other body areas.
The next raise your risk of a brain abscess:
• A weakened defense mechanisms (such as in AIDS patients)
• Chronic disease, for example cancer or Osler-Weber-Rendu syndrome
• Drugs that suppress the defense mechanisms (corticosteroids or chemotherapy)
• Right-to-left heart shunts, usually result of congenital cardiovascular disease


Symptoms
Symptoms may develop slowly, during a period of 2 weeks, or they might develop suddenly. They might include:
• Changes in mental status
• Confusion
• Decreasing responsiveness
• Drowsiness
• Eventual coma
• Inattention
• Irritability
• Slow thoughts
• Decreased movement
• Decreased sensation
• Decreased speech (aphasia)
• Fever and chills
• Headache
• Language difficulties
• Loss of coordination
• Loss of muscle function
• Seizures
• Stiff neck
• Vision changes
• Vomiting


Signs and tests
A brain and central nervous system (neurological) exam will often show increased intracranial pressure and issues with brain function.
Tests to identify a brain abscess can include:
• Blood cultures
• Chest x-ray
• Complete blood count (CBC)
• Head CT scan
• Electroencephalogram (EEG)
• MRI of head
• Testing for that presence of antibodies to organisms for example Toxoplasma gondii and Taenia solium
A needle biopsy is generally performed to identify the reason for the infection.

Treatment
A brain abscess is really a medical emergency. Pressure within the skull may become sufficient to be life threatening. You will have to stay in the hospital before the condition is stable. Many people may need life support.
Medication, not surgery, is usually recommended if you have:
• Several abscesses (rare)
• A small abscess (under 2 cm)
• An abscess deep within the brain
• An abscess and meningitis
• Shunts within the brain for hydrocephalus (in some instances the shunt may need to be removed temporarily or replaced)
• Toxoplasma gondii infection inside a person with HIV
Antibiotics is going to be prescribed. Antibiotics that actually work against a number of different bacteria (broad spectrum antibiotics) are most frequently used. You may be prescribed a number of different types of antibiotics to ensure treatment works.
Antifungal medications can also be prescribed if the infection is probably caused by a fungus.
Immediate treatment may be required if an abscess is injuring brain tissue by pressing onto it, or there is a large abscess having a large amount of swelling around that it's raising pressure within the brain.


Surgery is needed if :
• Pressure within the brain continues or worsens
• The brain abscess does not get smaller after medication
• The brain abscess contains gas (made by some types of bacteria)
• The brain abscess might break open (rupture)
Surgery includes opening the skull, exposing the mind, and draining the abscess. Laboratory tests in many cases are done to examine the fluid. It will help identify what is causing the problem, so that more appropriate antibiotics or antifungal drugs could be prescribed.
The surgical treatment used depends on the dimensions and depth from the abscess. The entire abscess may be removed (excised) if it's near the surface and enclosed inside a sac.
Needle aspiration guided by CT or MRI scan may be required for a deep abscess. In this procedure, medications might be injected directly into the mass.
Certain diuretics and steroids could also be used to reduce swelling from the brain.

IMAGINATION REALITY FLOW IN OPPOSITE DIRECTIONS IN THE BRAIN

As real as that daydream may seem, its path through your brain runs opposite reality.

Aiming to discern discrete neural circuits, researchers at the University of Wisconsin-Madison have tracked electrical activity in the brains of people who alternately imagined scenes or watched videos.

"A really important problem in brain research is understanding how different parts of the brain are functionally connected. What areas are interacting? What is the direction of communication?" says Barry Van Veen, a UW-Madison professor of electrical and computer engineering. "We know that the brain does not function as a set of independent areas, but as a network of specialized areas that collaborate."

Van Veen, along with Giulio Tononi, a UW-Madison psychiatry professor and neuroscientist, Daniela Dentico, a scientist at UW-Madison's Waisman Center, and collaborators from the University of Liege in Belgium, published results recently in the journal NeuroImage. Their work could lead to the development of new tools to help Tononi untangle what happens in the brain during sleep and dreaming, while Van Veen hopes to apply the study's new methods to understand how the brain uses networks to encode short-term memory.

During imagination, the researchers found an increase in the flow of information from the parietal lobe of the brain to the occipital lobe -- from a higher-order region that combines inputs from several of the senses out to a lower-order region.

In contrast, visual information taken in by the eyes tends to flow from the occipital lobe -- which makes up much of the brain's visual cortex -- "up" to the parietal lobe.

"There seems to be a lot in our brains and animal brains that is directional, that neural signals move in a particular direction, then stop, and start somewhere else," says. "I think this is really a new theme that had not been explored."

The researchers approached the study as an opportunity to test the power of electroencephalography (EEG) -- which uses sensors on the scalp to measure underlying electrical activity -- to discriminate between different parts of the brain's network.

Brains are rarely quiet, though, and EEG tends to record plenty of activity not necessarily related to a particular process researchers want to study.

To zero in on a set of target circuits, the researchers asked their subjects to watch short video clips before trying to replay the action from memory in their heads. Others were asked to imagine traveling on a magic bicycle -- focusing on the details of shapes, colors and textures -- before watching a short video of silent nature scenes.

Using an algorithm Van Veen developed to parse the detailed EEG data, the researchers were able to compile strong evidence of the directional flow of information.

"We were very interested in seeing if our signal-processing methods were sensitive enough to discriminate between these conditions," says Van Veen, whose work is supported by the National Institute of Biomedical Imaging and Bioengineering. "These types of demonstrations are important for gaining confidence in new tools."

CITY AIR CAN DAMAGE BRAIN STRUCTURES

Air pollution, even at moderate levels, has long been recognized as a factor in raising the risk of stroke. A new study led by scientists from Beth Israel Deaconess Medical Center and Boston University School of Medicine suggests that long-term exposure can cause damage to brain structures and impair cognitive function in middle-aged and older adults

Writing in the May 2015 issue of Stroke, researchers who studied more than 900 participants of the Framingham Heart Study found evidence of smaller brain structure and of covert brain infarcts, a type of "silent" ischemic stroke resulting from a blockage in the blood vessels supplying the brain.

The study evaluated how far participants lived from major roadways and used satellite imagery to assess prolonged exposure to ambient fine particulate matter, particles with a diameter of 2.5 millionth of a meter, referred to as PM2.5. These particles come from a variety of sources, including power plants, factories, trucks and automobiles and the burning of wood. They can travel deeply into the lungs and have been associated in other studies with increased numbers of hospital admissions for cardiovascular events such as heart attacks and strokes.

"This is one of the first studies to look at the relationship between ambient air pollution and brain structure," says Elissa Wilker, ScD, a researcher in the Cardiovascular Epidemiology Research Unit at Beth Israel Deaconess Medical Center. "Our findings suggest that air pollution is associated with insidious effects on structural brain aging, even in dementia- and stroke-free individuals."

Study participants were at least 60 years old and were free of dementia and stroke. The evaluation included total cerebral brain volume, a marker of age-associated brain atrophy; hippocampal volume, which reflect changes in the area of the brain that controls memory; white matter hyperintensity volume, which can be used as a measure of pathology and aging; and covert brain infarcts.

The study found that an increase of only 2µg per cubic meter in PM2.5, a range commonly observed across metropolitan regions in New England and New York, was associated with being more likely to have covert brain infarcts and smaller cerebral brain volume, equivalent to approximately one year of brain aging.

"These results are an important step in helping us learn what is going on in the brain," Wilker says. "The mechanisms through which air pollution may affect brain aging remain unclear, but systemic inflammation resulting from the deposit of fine particles in the lungs is likely important."

"This study shows that for a 2 microgram per cubic meter of air (μg/m3) increase in PM2.5, a range commonly observed across major US cities, on average participants who lived in more polluted areas had the brain volume of someone a year older than participants who lived in less polluted areas. They also had a 46 percent higher risk of silent strokes on MRI," said Sudha Seshadri, MD, a Professor of Neurology at Boston University School of Medicine and Senior Investigator, the Framingham Study.

"This is concerning since we know that silent strokes increase the risk of overt strokes and of developing dementia, walking problems and depression. We now plan to look at more the impact of air pollution over a longer period, its effect on more sensitive MRI measures, on brain shrinkage over time, and other risks including of stroke and dementia."

In addition to Wilker, who is also affiliated with the Exposure Epidemiology and Risk Program in the Department of Environmental Health at the Harvard T.H. Chan School of Public Health (HSPH), and Seshadri, co-authors include: Sarah R. Preis, ScD, of the Boston University School of Public Health, Department of Biostatistics (BUSPH) and the Framingham Heart Study (FHS); Alexa S. Beiser, PhD, of BUSPH, FHS and the Boston University School of Medicine Department of Neurology (BUSM); Philip A. Wolf, MD, of FHS and BUSM; Rhoda Au, PhD of BUSM; Ital Kloog, PhD, of the Department of Geography and Environmental Development , Ben-Gurion University of the Negev, Beer Sheva, Israel; Wenyuan Li, MS, of the Department of Epidemiology of HSPH; Joel Schwartz, PhD, of HSPH; Petros Koutrakis, PhD of HSPH; Charles DeCarli, MD, of the Department of Neurology and Center for Neuroscience, University of California, Davis; and Murray Mittleman, MD, DrPH, of BIDMC and HSPH.

Brain Implants To Control Pain The Way Forward

Today's post from painresearchforum.org (see link below) is one of those that gives hope for the future but makes us wish that the future was a little bit closer by. It talks about transcranial magnetic stimulation, which means that drugs can be avoided by means of an implant in the brain which alters circuit activity in the brain itself. This means that pain signals can be interrupted, or controlled. It's a complex, scientific article but simply enough explained to give you a good idea of what is meant. The article does warn that this procedure is not without its doubters and maybe risks and needs to be refined so that its results prove beyond doubt that it's an effective treatment. However, such warnings are reassuring to the reader that it's being taken seriously and it's clearly a promising development for future pain control without having to resort to drugs and medications. Another case of 'watch this space'.


Transcranial Magnetic Stimulation: The Next Wave in Pain Treatment?
Non-invasive technique shows promise but needs more study
by Stephani Sutherland on 3 Oct 2013 
 
Electrical stimulation of the motor cortex was established as an effective treatment for pain 20 years ago, but the risks and drawbacks of surgically implanting electrodes in the brain keep many patients from pursuing this invasive treatment (Tsubokawa et al., 1991; Kurata, 1993; Nguyen et al., 2011). What if there was a safer, non-invasive way to deliver analgesic neurostimulation? Transcranial magnetic stimulation (TMS) holds out promise as just such a next-generation pain treatment. In TMS, a magnetic field generated outside the head alters circuit activity inside the brain. TMS was approved in 2008 by the U.S. Food and Drug Administration for treatment of major depression, and researchers are investigating TMS for a number of other neurological conditions, including chronic, intractable pain.

Anne Louise Oaklander, a neurologist and pain researcher at Massachusetts General Hospital, Boston, US, said there is much work to be done, but the potential payoff of TMS for pain makes it well worth pursuing. “It has a huge potential advantage over pain medications,” she said. Drugs move indiscriminately throughout the body, often causing side effects at non-target tissues that limit their use or even prevent them from getting into the clinic. TMS, by contrast, delivers its therapeutic effects directly to the brain, with only minor, local side effects. “That is the trump card of TMS over drugs,” Oaklander said.

The evidence

Because TMS can modulate brain circuits safely and painlessly, the technique has had tremendous utility for studying pain processing, said Jean-Pascal Lefaucheur, a pioneer in the field of neurostimulation for pain at the Université Paris-Est, Créteil, France. Lefaucheur and his colleagues recently reviewed some of the hundreds of small studies that have examined the effects of TMS on evoked pain in experimental settings (Mylius et al., 2012). (In a separate review, Lefaucheur and colleagues recently discussed the mechanisms of action and the clinical indications of TMS for non-invasive stimulation therapy of pain disorders; see Nizard et al., 2012.)

Clinically, TMS is routinely used as a screening technique to predict a patient’s reaction to cortical stimulation before surgical implantation of electrodes, said Lefaucheur. A person who responds to TMS will almost always benefit from brain stimulation with implanted electrodes, he said. If a patient could receive the same benefit without implantation surgery, all the better.

But few studies have addressed the technique’s clinical efficacy. A 2010 Cochrane Review of non-invasive brain stimulation aimed at chronic pain looked at the accumulated data and concluded that high-frequency TMS showed a small but consistent reduction in patient-reported pain scores compared to sham treatment (O’Connell et al., 2010). Most of the studies’ participants had chronic, intractable neuropathic pain, and TMS produced a small and transient decrease in pain scores by about 15 percent for up to a week. However, inadequate sham controls and blinding may have exaggerated this effect, said lead author Neil O’Connell, Brunel University, Uxbridge, UK.

Although the pooled data involving just 368 subjects in 19 trials did not provide Neil O’Connell evidence of a clinically meaningful, long-term analgesic effect of TMS, O’Connell said one could yet emerge with further study. It is difficult to synthesize the results of small, heterogeneous studies, he told PRF. While it would be premature to roll out TMS clinically for pain, “I absolutely encourage scientists to study it more,” O’Connell said. “I am not saying it will not be useful [in the clinic], just that substantial uncertainty remains.” An updated review now in preparation will include more studies, but the conclusions for TMS will not change drastically, O’Connell said.

The rationale

All brain stimulation techniques work by activating neural circuitry. With TMS, a figure eight-shaped plastic paddle containing a coiled wire is placed over the head and briefly charged with high-intensity current, inducing a magnetic field that passes into the brain. Just as a wire placed in a magnetic field will carry current, so do axons. Neurostimulation therapy, Lefaucheur explained, prompts axons to fire action potentials and thereby influences circuits. “It is not [just] a local stimulation. You can stimulate local, short circuits or circuits with distant projections,” he said. Accordingly, TMS of the richly connected cortex can modulate the activity of structures deep within the brain.

Perhaps because its effects go beyond the cortex, David Yeomans TMS seems to affect different aspects of the experience of pain. “Pain is not a monolithic entity,” said David Yeomans, a pain researcher at Stanford University, California, US. Just as pain can arise from a variety of sources, so does it vary in its qualities and characteristics—for example, our discriminative sense feels the bodily sensation of pain, but the emotional aspects of pain cause our suffering.

Cortical stimulation seems to affect both these components, said Lefaucheur. Improvement of the sensory discrimination of pain might arise from modulation of descending inhibition circuits, which pass through the thalamus en route to brainstem structures and the spinal cord. In contrast, changes in the emotional aspects of pain likely arise from effects on the brain’s limbic circuitry, he explained.

Like any treatment, people do not respond uniformly to TMS; patients may see improvement in one aspect of the pain experience but not the other.

In practice

Further complicating the clinical understanding of TMS are the endless variations in its delivery. In clinical studies, the motor cortex has emerged as the clear winner in terms of where to target TMS for pain; the few studies that were aimed at dorsolateral prefrontal cortex—the bullseye for treating depression—were ineffective for pain (O’Connell et al., 2010). But the clarity ends there when it comes to the details of effective stimulation. Where, for example, within the motor cortex should one stimulate? One might aim intuitively at the cortical real estate representative of the painful area, but experts agree that the analgesic effects do not correspond to the somatotopic map.

Repetitive TMS (rTMS), in which a series of pulses is delivered in rapid succession within a single session, has emerged as the preferred method, but the protocol can be highly variable in details such as pulse frequency, stimulation intensity, and timing and duration of the treatments—for how long and how often should rTMS be delivered? The exact best technique is likely to vary for different people with different types of pain. Most clinical studies have used a pulse frequency somewhere between 1 and 10 hertz, with high-frequency stimulation consistently producing better effects than low-frequency (O’Connell et al., 2010).

It now seems clear that any long-lasting effects on pain will require multiple sessions of rTMS. In addition to the clinical evidence for the treatment’s transient nature, one current theory of how rTMS works also fits with the need for ongoing sessions. Multiple sessions of rTMS might affect the brain’s connectivity much like learning does. When you learn to play the piano or speak a new language, Oaklander said, “you create new synapses and you lose others; you change your brain.” If TMS engages the same types of synaptic plasticity, many treatments might be required to reshape signaling in circuits molded by chronic pain. As for how many, Oaklander said, “Nobody knows how often it needs to be repeated.” Treatments might be required daily at first and then as often as weekly for months or even years.

The updated Cochrane Review will include several studies of multiple sessions, O’Connell said, which were absent from the 2010 review. In one recent small study, a course of 14 rTMS sessions over 21 weeks for fibromyalgia resulted in long-term improvements in pain and quality-of-life scores (Mhalla et al., 2011). But even repeated treatments might not change the brain enough to provide lasting relief for some. The first randomized, multicenter, sham-controlled trial of repeated rTMS for neuropathic pain showed that 10 daily 5 Hz sessions provided only short-lived benefits with no cumulative effects (Hosomi et al., 2013).

Youichi Saitoh, a neurosurgeon at Osaka University in Japan and lead author of that study, believes that relief from neuropathic pain will require indefinite treatment with rTMS. Even in patients with implanted electrodes who have used neurostimulation for 10 years, analgesia does not last beyond about a day, Saitoh told PRF in an email. That leads him to think that rTMS does not lead to permanent neuroplastic changes in the pain processing system, he said.

Some researchers are investigating whether multiple sessions of rTMS cause structural remodeling in the brain. Neuropathic pain leads to well-documented structural changes in the brain, for example in the cingulate cortex (May, 2008). Yeomans and his colleagues plan to use brain imaging to investigate whether those changes might be reversed following a course of treatment with rTMS.

In practice, the delivery of TMS over multiple sessions remains a challenge because of the need to reproducibly target a specific brain area from outside of the head. Newly developed magnetic resonance imaging (MRI)-guided neuro-navigation can help the technician to hit the intended mark, but it remains to be seen whether the exceedingly expensive technique will be worth the price tag.

The cutting edge

One property—some would say limitation—of TMS is that it can only reach regions that lie within centimeters of the brain’s surface. Could pain pathways be better

In MRI-guided TMS, the operator holds the figure-eight coil to the patient’s scalp while monitoring the brain stimulation site on the three-dimensional MRI. Stereotactic spheres mounted on the coil identify its position relative to the spheres on the goggles that localize the patient’s head. Credit: Roi Treister, Massachusetts General Hospital, Boston, UStargeted at deeper structures? Several groups are asking that question. Brainsway, a company in Israel, has developed an “H-coil” to deliver what they call deep TMS. In a recent study, researchers used the H-coil to target the area of the motor cortex representing the leg, deep in the central sulcus, in subjects with diabetic neuropathy and saw pain relief that lasted up to three weeks (Onesti et al., 2013). In other work, Yeomans and his collaborators used four coils and what he described as “high-level math” to model how the combined coils might “shape” magnetic fields to direct currents deep into the brain (Tzabazis et al., 2013). They aimed at the dorsal anterior cingulate cortex (dACC), an area Yeomans says is activated by any experience of pain, according to neuroimaging studies. In their study, both acute pain in healthy subjects and chronic pain in subjects with fibromyalgia were attenuated by rTMS.

Although leading researchers in the field were supportive of these exploratory forays into the deeper reaches of TMS, they overwhelmingly agreed that what is most needed is a better fundamental understanding of the technique. Who might benefit most from TMS—people with neuropathic pain or other forms of pain? What is the optimal stimulation site, at what device settings, when and for how long? And what will benefits look like? How might TMS treatment interact with analgesic drugs? All of these basic questions remain unanswered. “It is a very complicated problem,” said Lefaucheur. “We need a large series of patients to clearly determine the correlations” among all these factors, he said.

O’Connell agreed and in a 2011 editorial (O’Connell and Wand, 2011) argued that rather than develop new coil configurations, researchers should prioritize robust Anne Louise Oaklander but basic studies of TMS. “Large, well-controlled studies are needed to test whether that early promise is real,” he said. Oaklander and her team recently wrote a review of TMS (Treister et al., 2013, in press in Rambam Maimonides Medical Journal) and have applied for funding for the planning stage of a large-scale clinical trial of TMS for neuropathic pain. This October, the Radcliffe Institute of Harvard University will host a gathering of scientists, clinicians, and regulatory agents to set out a path to designing such a trial. (Click here for more information; interested researchers are invited to a poster session and reception associated with the workshop.)

Other non-invasive stimulation techniques are being investigated, too, including transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES), in which electrodes applied to the scalp deliver low-intensity current directly. Much fewer data are available for these modalities compared to TMS: The Cochrane review of six small studies suggested tDCS might provide a slight benefit for pain, but the updated review of data suggests no significant effect over sham stimulation, O’Connell said. CES appeared to provide no benefit in four studies reviewed.

The bottom line

Even if the promise of TMS for pain holds up, the technique surely will not be a panacea. “The main limitation for TMS is the short duration of its [analgesic] effect,” said Lefaucheur. “It may not be feasible for some refractory, chronic neuropathic pain,” he said, considering the ongoing need for treatment that is costly, time-consuming, and requires technical expertise for delivery. Lefaucheur has had several patients with neuropathic pain who initially shunned electrode implantation for rTMS, but after a year of the toil of monthly treatments, they eventually opted for surgery.

In Japan, Saitoh and his colleagues are working to make daily rTMS treatment more accessible by developing a cheap, user-friendly rTMS machine for everyday home use. He hopes such a device will eliminate the need for electrode implantation.

Overall, TMS may be more useful to treat acute forms of pain and pain that is not so refractory to other treatments, Lefaucheur concluded. In treating depression, TMS is often used for a few days during an acute depressive episode, and “there can be a synergy between stimulation and [antidepressant] drugs,” Lefaucheur said. But with refractory, chronic pain, “the pain is constant, and the drugs do not work well.” Such conditions may require ongoing treatment in repeated sessions.

Despite the caveats and the need for more study, researchers were hopeful that rTMS could turn out to be useful in the pain clinic. David Brock, Medical Director at Neuronetics, Malvern, Pennsylvania, US, a company that makes the TMS machines widely used in clinics for depression, likens TMS to a Swiss Army knife. “We have figured out how to use one blade—for depression—but it has so many other potential tools. We just have to figure out how to use them,” he said. If TMS can change the disease state of chronic pain without drugs, as it has for depression, Brock said, “that would be a real boon to patients and society.”

Stephani Sutherland, PhD, is a neuroscientist, yogi, and freelance writer in Southern California.

http://www.painresearchforum.org/news/32343-transcranial-magnetic-stimulation-next-wave-pain-treatment

Light Treament On The Brain To Reduce Nerve Pain

Today's interesting post from sciencedaily.com (see link below) looks at how a small area of the brain can be stimulated by directed light frequencies to control pain signals in the neurons. The difficulty lies in making sure that we still sense the pain signals that we need to sense (touching a hot surface, avoiding injury etc) and that not all pain signals are 'switched off' by the process. The ever-heroic lab mice are the current recipients of the research but hopefully it will eventually translate into something practical that humans can use. It would certainly be less invasive than many other treatments.

Optogenetic stimulation of the brain to control pain demonstrated in study 
Date: February 26, 2015 Source: University of Texas at Arlington 

Summary:

New research reveals for the first time how a small area of the brain can be optically stimulated to control pain. Researchers found that by using specific frequency of light to modulate a very small region of the brain called the anterior cingulate cortex, or ACC, they could considerably lessen pain in laboratory mice.

A new study by a University of Texas at Arlington physics team in collaboration with bioengineering and psychology researchers shows for the first time how a small area of the brain can be optically stimulated to control pain.

Samarendra Mohanty, an assistant professor of physics, leads the Biophysics and Physiology Lab in the UT Arlington College of Science. He is co-author on a paper published online Wednesday by the journal PLOS ONE.

Researchers found that by using specific frequency of light to modulate a very small region of the brain called the anterior cingulate cortex, or ACC, they could considerably lessen pain in laboratory mice. Existing electrode based ACC stimulation lacks specificity and leads to activation of both excitatory and inhibitory neurons.

"Our results clearly demonstrate, for the first time, that optogenetic stimulation of inhibitory neurons in ACC leads to decreased neuronal activity and a dramatic reduction of pain behavior," Mohanty said. "Moreover, we confirmed optical modulation of specific electrophysiological responses from different neuronal units in the thalamus part of the brain, in response to particular types of pain-stimuli."

The research focused on chemical irritants and mechanical pain, such as that experienced following a pinprick or pinch. Mohanty said the results could lead to increased understanding of pain pathways and strategies for managing chronic pain, which often leads to severe impairment of normal psychological and physical functions.

"While reducing the sensation for chronic pain by optical stimulation, we still want to sense certain types of pain because they tell us to move our hands or legs away from something that is too hot or that might otherwise hurt us if we get too close," Mohanty said.

Young-tae Kim, a UT Arlington associate professor of bioengineering and study co-author, said the research could "possibly lead to less invasive methods for treating more severe types of pain without losing important emotional, sensing and behavioral functions."

Story Source:

The above story is based on materials provided by University of Texas at Arlington. Note: Materials may be edited for content and length.

Journal Reference:
Ling Gu, Megan L. Uhelski, Sanjay Anand, Mario Romero-Ortega, Young-tae Kim, Perry N. Fuchs, Samarendra K. Mohanty. Pain Inhibition by Optogenetic Activation of Specific Anterior Cingulate Cortical Neurons. PLOS ONE, 2015; 10 (2): e0117746 DOI: 10.1371/journal.pone.0117746

http://www.sciencedaily.com/releases/2015/02/150226101656.htm

In The Mind Or In The Brain Is Your Nerve Pain Worse Than It Should Be

Today's post from painscience.com (see link below) is really addressed at doctors and other health professionals who are treating patients with chronic pain but it's safe to assume that those patients themselves will gain a tremendous amount of insight into their own problems by reading this article. If any patient knows about misleading pain signals, it's the nerve pain patient and the ideas about central sensitization that this article expounds are directly relevant to neuropathy sufferers. Understanding how your own pain experience works will give you a heads up into how better to deal with it. How do we know if our pain is worse because the pain signals say it is and even perversely promote further pain? We don't is the answer but accepting the very idea, will help us psychologically  create coping strategies. Yep, mind over matter is a cliche but if we can identify when the pain is worse than it should be, then we just may be able to reduce it ourselves without taking yet more pills. You need to read the article to get the gist but don't worry, it's readable and relevant and you won't be bogged down in scientific jargon.

Central Sensitization in Chronic Pain
by Paul Ingraham, Vancouver, Canada bio updated November 17 2016 (first published 2011)
 
Pain itself can change how pain works, resulting in more pain with less provocation

Pain itself often modifies the way the central nervous system works, so that a patient actually becomes more sensitive and gets more pain with less provocation. That sensitization is called “central sensitization” because it involves changes in the central nervous system (CNS) in particular — the brain and the spinal cord. Sensitized patients are not only more sensitive to things that should hurt, but also to ordinary touch and pressure as well, which obviously should not hurt. Their pain also “echoes,” fading more slowly than in other people.


This first section is a direct jargon-to-English translation of an important scientific paper by Clifford Woolf, a rock star of a pain researcher, published in Pain in Oct 2010. Everyone needs to know this: it’s owner’s manual stuff. After the translation, I offer some of my own ideas about what it all means for patients and professionals.

In more serious cases, the extreme over-sensitivity is obvious. But in mild cases — which are probably quite common — patients cannot really be sure that pain is actually worse than it “should” be, because there is nothing to compare it to except their own memories of pain.

This rather awful thing is actually quite easy to create in the lab, like a mad scientist’s monster. Any kind of noxious stimuli can trigger the change — anything that hurts skin, muscles or organs — and it can be reliably detected with special equipment. The role of sensitization in several common diseases12 has been proven and well-documented, and may in particular be provoked by (common) muscle pain.3 It can also persist and worsen in the absence without apparent provocation. This rather awful thing is actually quite easy to create in the lab, like a mad scientist’s monster.

Indeed, this neurological meltdown is such a consistent complication of other painful problems that some researchers now believe central sensitization is actually a major common denominator in most difficult pain problems. That is, it may be the nearly universal factor that puts the “chronic” in chronic pain, giving all such problems shared characteristics regardless of how it got started — not the cause of the pain, but perhaps the cause of its chronicity.

The existence of central sensitization is quite well established. What is still unknown is why it happens to some people and not others. Both environment and genetics are probably factors — aren’t they always? — but which genes, and what things in the environment? We just do not know yet.

Another unfortunate gap in our scientific knowledge is that there are no clear criteria for diagnosing central sensitization. There is no easy lab test or checklist that can confirm it.4 It could be present in nearly any difficult case of chronic pain, but it’s not a sure thing — the pain could still be coming from a continuing problem in the tissue, with or without central sensitization muddying the waters.
Hallucinating pain

One easy way to understand central sensitization is that it causes pain hallucinations: a bogus perception, but instead of seeing lizards on the walls, you feel pain that makes no sense.

There are some related conditions that are easier to understand. For instance, hyperacusis is an increased sensitivity to sounds, usually specific frequencies and volumes. Imagine a restaurant that sounds as loud as a rock concert. My father, a Vietnam veteran with PTSD, suffered from this condition for a couple years: he was hallucinating loudness. He spend a long time re-calibrating his sense of what “loud” is. A big part of that was asking my mother for an opinion on the loudness, and trusting her judgement: yes, it really is loud in here or no, this really isn’t very loud. By frequently checking his perception against a healthy, objective assessment, he was able to slowly adjust his subjective volume scale.

But pain hallucination is a completely personal and internal experience, and there’s no good way to check the validity of your pain. No one can tell you, no, that really isn’t very painful. They cannot know.5

Pain hallucinations do not mean that pain isn’t real. It usually means it’s just a too loud interpretation of something that would hurt even if you weren’t sensitized. It’s also real in the same sense that hallucinations are caused by real neurological problems. When you feel pain you’re not supposed to, it just means that the nervous system itself is damaged, rather than the tissues it’s supposed to be reporting on. The pain system is borked.





Health care for pain problems remains overwhelmingly preoccupied with structural and biomechanical causes — they exist, but therapists hoping to diagnose pain that way are generally barking up the wrong tree. The last 20 years of pain science strongly suggest that neurology is by far the most important factor in most chronic pain.

Making a bad situation worse: the trouble with not knowing the neurology

Even the clearest localization of pain in one area may, in fact, be originating from a distant area …. The reference of pain implies the existence of convergence of inputs within the spinal cord. This leads to the necessary involvement in central neural circuits in the simplest of peripheral disorders. It also leads to the possibility that the basic disorder is entirely central …


Professor Patrick D. Wall, FRS, DM, FRCP, in the Foreword to Muscle Pain: Understanding its nature, diagnosis and treatment

Pain is a warning system, and central sensitization is therefore a disease of over-sensitivity to threats to the organism — a hyperactive warning system. When physical therapists, massage therapists and chiropractors treat a chronic pain patient too intensely, they are going to trigger that alarm system, and quite possibly make the situation worse instead of better.

Central sensitization is bad news, but worse still is how few health care professionals are aware of the neurology and make things worse with careless or even deliberately rough, no-pain-no-gain treatment. It’s bad enough that ignorance of central sensitization leads to wild goose chases and patients riding a merry-go-round of expensive and ineffective therapies, but many kinds of therapy are also quite painful — and can make the problem worse. With tragic irony, the most likely victims are also the most vulnerable and desperate patients, patients going through the therapy grinder, their hopes leading them right into the hands of the most intense therapists.

The science of central sensitization is not all that new, but its surprising clinical implications are still emerging, and resisted by many health care professionals thinking well inside the box they were taught in. Ignorance of central sensitization leads to wild goose chases and patients riding a merry-go-round of expensive and ineffective therapies. Their minds are firmly made up that pain is mainly “in” tissues, something wounded or irritated inside your meaty, gristly anatomy. Of course, trouble with tissues is important too — but the science has shown us that it is much less dominant a factor than anyone used to think. Countless studies now have shown a surprising, counter-intuitive disconnect between symptoms and problems plainly visible on scans.6 Or, in rheumatoid arthritis, patients often suffer more pain than expected from just the inflammatory erosion of their joints7 — and sensitization is probably the explanation for the “spread” of pain beyond their joints.8 Factors like poor sleep quality may drive up sensitization, and thus are more of a cause of pain than anything going on in the tissues.9

It’s actually quite astonishing how little pain is caused by some seemingly dramatic issues in your tissues! “The evidence that tissue pathology does not explain chronic pain is overwhelming (e.g., in back pain, neck pain, and knee osteoarthritis).” (Moseley)

It all starts to make a lot more sense when you understand how the your pain system works — that pain is strongly regulated by the brain.

Professionals may pay some lip service to the importance of integrating neurological considerations into treatment, but their respect is often more poetic and politically correct than practical.10 Care for chronic pain of all kinds needs to soothe and normalize the nervous system — not challenge it with vigorous manipulations.
What should patients do? (Professionals should read this too!)

Patients with stubborn pain problems should start trying to decide if they are experiencing “too much” pain — more than seems to “make sense.” It’s not an easy question to answer. When we hurt, it always seems like a big deal! Again, it’s just like a patient with hyperacusis trying to figure out if sounds are actually too loud, or just seem that way. Unfortunately, a pain patient cannot ask anyone: “Does that seem really painful to you? Or is that just my central sensitization?”

ZOOM


You’ve got some nerve

Pay attention to this. Not much else matters if this part of you isn’t happy.

If you suspect that your nervous system is no longer giving you useful, sensible pain signals, then be extra cautious about painfully intense therapies and skeptical of biomechanical explanations for your pain (i.e. “you hurt because you have a short leg”) — such factors are only part of the picture, and probably the least important part. Make sure any professional you see is aware of the phenomenon of central sensitization, and start using that as a criteria for judging the quality of their services — if your doctor or therapist doesn’t act like they know what central sensitization is, take your business elsewhere.

You might go through quite a few professionals before finding one who shows some “sensitivity to sensitivity.”

Medications that work on the central nervous system11 are probably the most promising treatment for serious pain system dysfunction. Only a physician trained in the care of chronic pain can prescribe those medications. The best place to look for such a doctor is in a pain clinic — if you have serious chronic pain, you should start looking for one today.

Finally, regardless of whether or not central sensitization is actually happening in your body now, it always makes sense to be kind to your central nervous system. Make your life “safer” and less stressful. Gentler. Easier. Centralization of pain is the process of the central nervous system’s “opinion” of the situation becoming more important than the actual state of the tissues. This is not an “all in the head” problem, but a “strongly affected by the head” problem, like an ulcer that is caused by a very real bug but is severely aggravated by stress.

When your CNS is “freaked out” and over-interpreting every signal from the tissues as more painful than it should, therapy becomes more about soothing yourself and feeling safe than about fixing tissues. Pain is, at a very fundamental level, all about your brain’s assessment of safety: unsafe things hurt. If your brain thinks you’re safe, pain goes down.

So, for the chronic pain sufferer, cultivating “life balance” and peacefulness is a logical foundation for recovery, more important than just a pleasing philosophy — and it’s a worthwhile challenge even if it fails as therapy, of course. This is what I always meant by the idea of “healing by growing up,” long before I had even heard of central sensitization.
What should professionals do? (Patients should read this too!)

At the end of this section, I provide some practical sensitization-friendly treatment principles in point form — but they follow almost automatically from education, which is the main thing. Professionals need to get their bums into gear and simply learn more about central sensitization and pain neurology generally. Once you’ve learned more about sensitization, it’s hard not to do start doing things differently.

Start deconstructing your assumptions about pain with my article on the follies and inconsistencies of structural models of pain, and also read Eyal Lederman’s more academic treatments of the same topic (on low back pain, and core strengthening). Then read Clifford Woolf’s excellent 2010 tutorial, “Central sensitization: Implications for the diagnosis and treatment of pain” — it’s heavy reading, but worth the mental exertion.

There are two websites that consistently produce good, readable, science-based information and resources about central sensitization and related topics: A massage therapist once inflicted extreme discomfort on my armpit because she believed that there were evil “restrictions” in there.Body In Mind and the NOI Group. Also, physical therapist Diane Jacobs is extremely active on Facebook, constantly sharing valuable information on this theme on her page, Neuroscience and Pain Science for Manual Physical Therapists.

Finally: please start treating pain patients like they might have a janky nervous system that is over-reacting to every possible perceived threat — and stop chasing the red herrings of subtle biomechanical problem of dubious clinical relevance, that are mostly nearly impossible to prove or treat anyway, and which often lead you to try to apply to much pressure to tissues. For example, a massage therapist once inflicted extreme discomfort on my armpit because she believed that there were evil “restrictions” in there and that she could rip her way to a cure of a shoulder problem I didn’t even really have. All she accomplished was to swamp my nervous system with nociception, and it could have been disastrous if I’d been a chronic pain patient.

Instead of trying to “fix” anything, seek to create (or at least contribute to) a felt experience of wellness. Make therapy pleasant, easy, and reassuring. Help the patient remember what it’s like to feel safe and good.

This transition can be immensely liberating: it can put an end to the wild goose chases for sources of pain in the tissues in many of your toughest cases.

Fundamentals of Treatment (aka Axioms of Function, by Greg Lehman)

These principles are described in detail in Don't Freak Out by Greg Lehman, BKin, MSc, DC, MScPT. All great points, but the most neglected, important, and relevant to sensitization is obviously 

Rule out red flags
Rule out serious tissue pathology
The body is strong and adaptable
Pain is more about sensitivity than about injury
Treatment is about finding the appropriate stressor
The patient is an active participant in their own care
Decorations (“Useful Though Not Fundamental Axioms”)
Gauge your treatments by assessing sensitivity
Manual therapy is an adjunct to fundamentals
Your assessment reinforces their belief in strength
Comprehensive capacity trumps assessment-driven correctives
Postural and movement assessments reveal habits but not flaws 

https://www.painscience.com/articles/central-sensitization.php

BRAIN CIRCUIT THAT THAT CONTROLS COMPULSIVE OVEREATING AND SUGAR ADDICTION DISCOVERED

Compulsive overeating and sugar addiction are major threats to human health, but potential treatments face the risk of impairing normal feeding behaviors that are crucial for survival. A study published January 29th in the journal Cell reveals a reward-related neural circuit that specifically controls compulsive sugar consumption in mice without preventing feeding necessary for survival, providing a novel target for the safe and effective treatment of compulsive overeating in humans

Although obesity and Type 2 diabetes are major problems in our society, many treatments do not tackle the primary cause: unhealthy eating habits," says senior study author Kay Tye of the Massachusetts Institute of Technology. "Our findings are exciting because they raise the possibility that we could develop a treatment that selectively curbs compulsive overeating without altering healthy eating behavior."

Compulsive overeating is a type of reward-seeking behavior, similar to drug addiction. But the major difference between the two behaviors is that eating is required for survival, underscoring the need to tease apart brain circuits involved in compulsive overeating versus normal feeding to develop safe and effective therapies. Tye and her team suspected that a neural pathway from the lateral hypothalamus to the ventral tegmental area might play an important role in compulsive overeating because these brain regions have been implicated in reward-related behaviors such as eating, sexual activity, and drug addiction.

To test this idea, Tye and her team used a technique called optogenetics, which involves genetically modifying specific populations of neurons to express light-sensitive proteins that control neural excitability, and then delivering either blue or yellow light through an optic fiber to activate or inhibit those cells, respectively. Activation of the pathway from the lateral hypothalamus to the ventral tegmental area caused well-fed mice to spend more time feeding and increased the number of times mice poked their nose into a port to receive a sugar reward, even when they had to cross a platform that delivered foot shocks to get to the reward. By contrast, inhibition of the same pathway reduced this compulsive sugar-seeking behavior without decreasing food consumption in hungry mice, suggesting that different neural circuits control feeding in hungry animals.

In an independent study also published January 29th in Cell, Garret Stuber of the University of North Carolina School of Medicine and his team similarly used an optogenetic approach in mice to identify neurons in the lateral hypothalamus that control both feeding and reward-seeking behavior. By imaging the activity of hundreds of individual lateral hypothalamus neurons as the mice freely explored an area with food or worked to obtain a sweet reward, they further uncovered distinct subsets of neurons that either mediate food-seeking behavior or respond to reward consumption.

According to Tye, it makes sense that brain circuits evolved to support binging on scarce, sugary foods whenever these valuable sources of energy become transiently available during certain seasons. But in the winter, it might be adaptive for separate neural circuits to drive hungry animals to eat whatever type of food is available but to consume less overall to ration out limited resources.

"However, in our modern day society, there is no scarcity of palatable foods, and high-sugar or high-fat foods are often even more available than fresh produce or proteins," Tye says. "We have not yet adapted to a world where there is an overabundance of sugar, so these circuits that drive us to stuff ourselves with sweets are now serving to create a new health problem. The discovery of a specific neural circuit underlying compulsive sugar consumption could pave the way for the development of targeted drug therapies to effectively treat this widespread problem."