Research Into Pain Shows That When People Expect More Pain, They Feel More Pain

A good study that’s needed to be done for a while.

Expect a shot to hurt and it probably will, even if the needle poke isn’t really so painful. Brace for a second shot and you’ll likely flinch again, even though — second time around — you should know better.

That’s the takeaway of a new brain imaging study published in the journal Nature Human Behaviour which found that expectations about pain intensity can become self-fulfilling prophecies. Surprisingly, those false expectations can persist even when reality repeatedly demonstrates otherwise, the study found.

“We discovered that there is a positive feedback loop between expectation and pain,” said senior author Tor Wager, a professor of psychology and neuroscience at the University of Colorado Boulder. “The more pain you expect, the stronger your brain responds to the pain. The stronger your brain responds to the pain, the more you expect.”

For decades, researchers have been intrigued with the idea of self-fulfilling prophecy, with studies showing expectations can influence everything from how one performs on a test to how one responds to a medication. The new study is the first to directly model the dynamics of the feedback loop between expectations and pain and the neural mechanisms underlying it.

Marieke Jepma, then a postdoctoral researcher in Wager’s lab, launched the research after noticing that even when test subjects were shown time and again that something wouldn’t hurt badly, some still expected it to.

“We wanted to get a better understanding of why pain expectations are so resistant to change,” said Jepma, lead author and now a researcher at the University of Amsterdam.

The researchers recruited 34 subjects and taught them to associate one symbol with low heat and another with high, painful heat.

Then, the subjects were placed in a functional magnetic resonance imaging (fMRI) machine, which measures blood flow in the brain as a proxy for neural activity. For 60 minutes, subjects were shown low or high pain cues (the symbols, the words Low or High, or the letters L and W), then asked to rate how much pain they expected.

Then varying degrees of painful but non-damaging heat were applied to their forearm or leg, with the hottest reaching “about what it feels like to hold a hot cup of coffee” Wager explains.

Then they were asked to rate their pain.

Unbeknownst to the subjects, heat intensity was not actually related to the preceding cue.

The study found that when subjects expected more heat, brain regions involved in threat and fear were more activated as they waited. Regions involved in the generation of pain were more active when they received the stimulus. Participants reported more pain with high-pain cues, regardless of how much heat they actually got.

“This suggests that expectations had a rather deep effect, influencing how the brain processes pain,” said Jepma.

Surprisingly, their expectations also highly influenced their ability to learn from experience. Many subjects demonstrated high “confirmation bias” — the tendency to learn from things that reinforce our beliefs and discount those that don’t. For instance, if they expected high pain and got it, they might expect even more pain the next time. But if they expected high pain and didn’t get it, nothing changed.

“You would assume that if you expected high pain and got very little you would know better the next time. But interestingly, they failed to learn,” said Wager.

This phenomenon could have tangible impacts on recovery from painful conditions, suggests Jepma.

“Our results suggest that negative expectations about pain or treatment outcomes may in some situations interfere with optimal recovery, both by enhancing perceived pain and by preventing people from noticing that they are getting better,” she said. “Positive expectations, on the other hand, could have the opposite effects.”

The research also may shed light on why, for some, chronic pain can linger long after damaged tissues have healed.

Whether in the context of pain or mental health, the authors suggest that it may do us good to be aware of our inherent eagerness to confirm our expectations.

“Just realizing that things may not be as bad as you think may help you to revise your expectation and, in doing so, alter your experience,” said Jepma.

Three Types of Depression Identified in Research for the First Time

More knowledge about the societal problem of depression should lead to more effective treatments for it.

According to the World Health Organization, nearly 300 million people worldwide suffer from depression and these rates are on the rise. Yet, doctors and scientists have a poor understanding of what causes this debilitating condition and for some who experience it, medicines don’t help.

Scientists from the Neural Computational Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), in collaboration with their colleagues at Nara Institute of Science and Technology and clinicians at Hiroshima University, have for the first time identified three sub-types of depression. They found that one out of these sub-types seems to be untreatable by Selective Serotonin Reuptake Inhibitors (SSRIs), the most commonly prescribed medicines for the condition. The study was published in the journal Scientific Reports.

Serotonin is a neurotransmitter that influences our moods, interactions with other people, sleep patterns and memory. SSRIs are thought to take effect by boosting the levels of serotonin in the brain. However, these drugs do not have the same effect on everyone, and in some people, depression does not improve even after taking them. “It has always been speculated that different types of depression exist, and they influence the effectiveness of the drug. But there has been no consensus,” says Prof. Kenji Doya.

For the study, the scientists collected clinical, biological, and life history data from 134 individuals — half of whom were newly diagnosed with depression and the other half who had no depression diagnosis- using questionnaires and blood tests. Participants were asked about their sleep patterns, whether or not they had stressful issues, or other mental health conditions.

Researchers also scanned participants’ brains using magnetic resonance imaging (MRI) to map brain activity patterns in different regions. The technique they used allowed them to examine 78 regions covering the entire brain, to identify how its activities in different regions are correlated. “This is the first study to identify depression sub-types from life history and MRI data,” says Prof. Doya.

With over 3000 measurable features, including whether or not participants had experienced trauma, the scientists were faced with the dilemma of finding a way to analyze such a large data set accurately. “The major challenge in this study was to develop a statistical tool that could extract relevant information for clustering similar subjects together,” says Dr. Tomoki Tokuda, a statistician and the lead author of the study. He therefore designed a novel statistical method that would help detect multiple ways of data clustering and the features responsible for it. Using this method, the researchers identified a group of closely-placed data clusters, which consisted of measurable features essential for accessing mental health of an individual. Three out of the five data clusters were found to represent different sub-types of depression.

The three distinct sub-types of depression were characterized by two main factors: functional connectivity patterns synchronized between different regions of the brain and childhood trauma experience. They found that the brain’s functional connectivity in regions that involved the angular gyrus — a brain region associated with processing language and numbers, spatial cognition, attention, and other aspects of cognition — played a large role in determining whether SSRIs were effective in treating depression.

Patients with increased functional connectivity between the brain’s different regions who had also experienced childhood trauma had a sub-type of depression that is unresponsive to treatment by SSRIs drugs, the researchers found. On the other hand, the other two subtypes — where the participants’ brains did not show increased connectivity among its different regions or where participants had not experienced childhood trauma — tended to respond positively to treatments using SSRIs drugs.

This study not only identifies sub-types of depression for the first time, but also identifies some underlying factors and points to the need to explore new treatment techniques. “It provides scientists studying neurobiological aspects of depression a promising direction in which to pursue their research,” says Prof. Doya. In time, he and his research team hope that these results will help psychiatrists and therapists improve diagnoses and treat their patients more effectively.

Scientific Research Shows Lavender’s Smell is Legitimately Relaxing

Using lavender candles rather than a drug with potentially terrifying side effects such as Xanax seems like one of the better ways (along with exercise) to reduce anxiety levels in this crazy world.

Lavender works its relaxing magic all around us: from garden borders to bath bombs to fabric softener. But why not in our hospitals and clinics? And what is the science behind the magic?

Research published in Frontiers in Behavioral Neuroscience shows for the first time that the vaporized lavender compound linalool must be smelt — not absorbed in the lungs- to exert its calming effects, which could be used to relieve preoperative stress and anxiety disorders.

Soothing scents

“In folk medicine, it has long been believed that odorous compounds derived from plant extracts can relieve anxiety,” says co-author Dr Hideki Kashiwadani of Kagoshima University, Japan.

Modern medicine has overlooked these scented settlers, despite a need for safer alternatives to current anxiolytic (anxiety-relieving) drugs like benzodiazepines.

Numerous studies now confirm the potent relaxing effects of linalool, a fragrant alcohol found in lavender extracts.

“However, the sites of action of linalool were usually not addressed in these studies,” Kashiwadani points out.

Many assumed that absorption into bloodstream via the airway led to direct effects on brain cell receptors such as GABAARs — also the target of benzodiazepines. But establishing the true mechanism of linalool’s relaxing effects is a key step in moving towards clinical use in humans.

A nose for success

Kashiwadani and colleagues tested mice to see whether it is the smell of linalool — i.e. stimulation of olfactory (odor-sensitive) neurons in the nose — that triggers relaxation.

“We observed the behavior of mice exposed to linalool vapor, to determine its anxiolytic effects. As in previous studies, we found that linalool odor has an anxiolytic effect in normal mice. Notably, this did not impair their movement.” This contrasts with benzodiazepines, and linalool injections, whose effects on movement are similar to those of alcohol.

However, crucially there was no anxiolytic effect in anosmic mice — whose olfactory neurons have been destroyed — indicating that the relaxation in normal mice was triggered by olfactory signals evoked by linalool odor.

What’s more, the anxiolytic effect in normal mice disappeared when they were pretreated with flumazenil, which blocks benzodiazepine-responsive GABAA receptors.

“When combined, these results suggest that linalool does not act directly on GABAA receptors like benzodiazepines do — but must activate them via olfactory neurons in the nose in order to produce its relaxing effects,” explains Kashiwadani.

Coming to theaters near you

“Our study also opens the possibility that relaxation seen in mice fed or injected with linalool could in fact be due to the smell of the compound emitted in their exhaled breath.”

Similar studies are therefore needed to establish the targets, safety and efficacy of linalool administered via different routes, before a move to human trials.

“These findings nonetheless bring us closer to clinical use of linalool to relieve anxiety — in surgery for example, where pretreatment with anxiolytics can alleviate preoperative stress and thus help to place patients under general anesthesia more smoothly. Vaporized linalool could also provide a safe alternative for patients who have difficulties with oral or suppository administration of anxiolytics, such as infants or confused elders.”

Research: Letting in Sunshine Helps Kill Germs Indoors

It’s flu season and so this can be especially useful to know around this time of year.

Even before Florence Nightingale advised that hospitals be designed to let daylight in, people observed that sunshine helps keep you healthy. But there was not much research to explain why that’s the case, especially inside buildings.

Researchers at the University of Oregon set up a study of dusty, dollhouse-size rooms to compare what happens in rooms exposed to daylight through regular glass, rooms exposed to only ultraviolet light and those kept dark. They used a mix of dust collected from actual homes in the Portland area and let the miniature rooms sit outdoors while keeping the insides at a normal room temperature.

After 90 days (because that’s how long dust can hang around, even if you vacuumed), they sampled the dust and analyzed the types of bacteria present.

What they found surprised them and confirmed what your grandmother already knew: Rooms exposed to daylight have fewer germs. In fact, the study showed that the lit rooms had about half the viable bacteria (those that are able to grow), compared with dark rooms. Rooms that were exposed only to UV light had just slightly less viable bacteria than ones exposed to daylight. Their research was published Wednesday in the journal Microbiome.

The study’s lead author, Ashkaan Fahimipour, a postdoctoral researcher at the University of Oregon’s Biology and the Built Environment Center, says he was surprised that the visible light and the UV light performed so similarly to keep bacteria down.

The researchers looked at both types of light because UV is known to be a good disinfectant and is used to clean drinking water. Yet typical window glass filters out most UV light.

Another surprising thing was the amount of microbes that were viable in dust. Earlier studies didn’t suggest it would be as much, says co-author Kevin Van Den Wymelenberg, co-director of the Biology and the Built Environment Center at the University of Oregon. That’s because indoor dust is like a desert — it’s too dry for most bacteria or other things to grow. This study found 12 percent of bacteria in dark rooms were viable compared to 6.8 percent in rooms with daylight and 6.1 percent in rooms exposed to UV light only.

While it may not sound like much, “6 percent of millions of cells is still a lot of microbes,” Van Den Wymelenberg says. “Until now, daylighting [illuminating a building with natural light] has been about visual comfort or broad health. But now we can say daylighting influences air quality.”

The daylit rooms in the study also had less of the types of bacteria associated with human skin, which people shed as they move around indoors, and more closely resembled outdoor bacterial communities. Some of the human-associated bacteria species that didn’t survive in the lighted rooms are from a family of bacteria known to cause respiratory disease.

In their future work, the researchers said they’d like to design studies to determine how much light is necessary to kill microbes so architects can begin to design buildings with that in mind.

Also, researchers have learned from trying to eradicate all germs in hospital and laboratory clean rooms that it’s really hard to get rid of microbes wholesale. “Sanitizing isn’t the best approach,” Fahimipour says. And some microbes are actually good for us, like the ones in yogurt. Someday, he says, “it may be better to enrich an indoor setting with microbes that are not harmful or even [with those that are] beneficial.”

Good Immunotherapy is Amazing at Treating Cancer — And It’s Unnecessarily Expensive

Drugs are cheap to produce — it’s things like unjust government-granted patent monopolies that allow pharmaceutical companies to charge exorbitant prices that make drugs expensive.

To quote economist Dean Baker’s latest October 2018 paper:

“Many items that sell at high prices as a result of patent or copyright protection would be free or nearly free in the absence of these government granted monopolies. Perhaps the most notable example is prescription drugs where we will spend over $420 billion in 2018 in the United States for drugs that would almost certainly cost less than $105 billion in a free market. The difference is $315 billion annually or 1.6 percent of GDP. If we add in software, medical equipment, pesticides, fertilizer, and other areas where these protections account for a large percentage of the cost, the gap between protected prices and free market prices likely approaches $1 trillion annually, a sum that is more than 60 percent of after-tax corporate profits.”

On to the article though.

Last week, researchers James Allison and Tasuku Honjo were awarded this year’s Nobel Prize in medicine for their work on cancer immunotherapies, heralded by the Nobel committee as “seminal discoveries” that “constitute a landmark in our fight against cancer.”

Immunotherapies like those developed on the basis of Allison and Honjo’s work are indeed an important step towards a whole new way to treat cancer, as well as a host of other chronic diseases. However, this Nobel award should remind us that these innovative therapies are out of reach for so many patients in the United States due to the exorbitant prices drug companies charge for them.

Just weeks before the Nobel announcement, oncologist Ezekiel Emmanuel wrote in a Wall Street Journal essay, “We Can’t Afford the Drugs That Could Cure Cancer,” that “a cure for cancer has become possible, even probable” with immunotherapies, but that our health system cannot afford their price tag. Just after the Nobel announcement, Vox reporter Julia Belluz reminded us that “the average cost of cancer drugs today is four times the median household income” (emphasis added).

Immunotherapies constitute a part of the class of drugs called biologics (as opposed to chemical pharmaceuticals) that have shown very promising results in treating many previously intractable conditions, such as multiple sclerosis, asthma, chronic pain, and Crohn’s disease, due to their ability to more precisely target individual diseased cells. Therefore it’s no surprise that currently most of the top 10 best-selling drugs worldwide are biologics.

[…]

If biologics really are the future of medicine, we must change the way prescription drugs are priced in the United States, or millions of patients will be left behind. One way to do that is to invest in public pharmaceuticals that can assure an adequate supply of and equitable access to essential medications.

Using Virtual Reality in Beneficial Ways

Virtual reality is technology that’s advancing from being fringe to something that’s gradually becoming implemented more in the 21st century. This trend will only continue with lower costs of materials for virtualization and improved software.

The way virtual reality works is obvious enough — some sort of apparatus that covers the eyes and is able to transmit visual of a virtual world is required. Virtual worlds of course will have sounds to make them more immersive, and perhaps in the future there will be an option to stimulate other senses as well. It isn’t unreasonable to expect the possibility of VR technology that somehow provides the replication of smell, taste, and feel. Eventually there is likely to be VR technology with direct brain stimulation too.

Virtual reality is often presented these days as a fun way to spend time through gaming, and while it can be beneficial to provide people with an escape that doesn’t involve hard drugs in a world that’s often crazy and fucked up, virtual reality has other uses that deserve to be known about more.

One of the most notable recent findings is a study finding that people recall information better through virtual reality. Since knowledge is power, the enhanced ability of people to recall knowledge would be helpful in a variety of scenarios, such as training people for meaningful work, keeping fond memories more effectively, and assisting in educational endeavors. This could be combined with other research finding that drawing pictures is a strong way to remember information.

Most people are not especially good multi-taskers — the research tells us that only a few percent of people are “super taskers,” or those with the ability to focus on multiple tasks well. For whatever reason this is, it’s a general principle that human beings tend to perform better when their primary focus is on one task at a given time. Virtual reality thus provides an immersive environment that should allow people to focus more on one task than a traditional 2D learning environment.

VR has been shown to reduce the fear children have for needles in one study. This makes sense due to the distraction from VR’s intense immersion. Since the fear of needles is a suffocating one for some children, something as simple as a VR experience of going to an amusement park or a beach would be immensely helpful.

There’s a problem of too many people avoiding vital vaccinations in the United States, leading to diseases that should have been extinguished in the 20th century suddenly making recurrences in certain parts of the country. This is another example of how technology can be used to solve a real problem and protect society.

VR’s distraction could be extended to surgeries where local anathesia is used, thus protecting people from pain. It has already been found that virtual reality therapy is effective at reducing pain in hospitalized patients. It isn’t entirely clear why, but it may be because the VR experience is so immersive that the brain is unable to concurrently process the pain stimuli along with the VR.

It has been theorized that people have a fixed capacity for attention, and it has also been thought that when people are expecting physical pain in the immediate future, they tend to feel it more intensely. This may be because instead of the pain being a surprise, the increased focus on it before the pain hits may cause it to be felt more strongly.

Virtual reality will also have an important role in the journalism of the future. Studies have found that VR makes journalism more immersive, such as the VR story about factory farming being successful at raising more awareness of the horrific treatment often endured by animals.

VR can thus be an effective tool at fighting corruption and injustice in an era where young people generally — for whatever reason — are reading less than past generations. It has been found that too much use of fantasy-like elements in VR distract from the realism of the story and can make them less credible, however.

VR has also been referred to as an “empathy machine.” It’s conceivable that VR could be used for rehabilitation — use of the technology has already shown promise at increasing empathy levels, and VR shows promising mental health treatment results. The immersive virtual experience of owning a body in VR space has at times shown to really have an impact at altering perceptions and making important impressions.

In sum, while interactions in real life will always have importance that’s often most meaningful, there are many ways that virtual reality may improve the livelihoods of others.

New Blood Test Offers Better or Equal Skin Cancer Detection Rate than a Biopsy

Skin cancer is the most common cancer in the world, and it’s the one that’s most easily treated when caught early. Since the blood test is less invasive than a biopsy, this new advance should be helpful in convincing more people to receive treatment early on.

It’s a world first. A newly developed blood test is capable of the early detection of melanoma, with over 80 percent accuracy.

It could help save thousands of lives, according to the Australian Edith Cowan University Melanoma Research Group scientists who developed the test.

Melanoma is the most deadly form of skin cancer, claiming 59,782 lives around the world in 2015. Australasia, North America and Europe are the regions most susceptible to the disease.

There’s good news. If caught early, the survival rate for melanoma climbs to 95 percent. But if you miss that early window, your chances will plummet to below 50 percent. This is what the blood test is designed to help prevent.

[…]

The blood test, called MelDX, works by detecting the antibodies the body produces as soon as melanoma develops. The team analysed 1,627 different types of antibodies, and narrowed them down to a combination of 10 that indicate the presence of melanoma in the body.

They then took blood from 104 people with melanoma and 105 healthy controls, and found that MelDX was capable of detecting melanoma with 81.5 percent accuracy.

More specifically, it was able to detect the cancer in 79 percent of the patients with melanoma; and has a false positive rate in only 16 percent in healthy patients.

The detection rate may actually be a little higher than the accuracy of skin biopsies, which, according to a 2012 study, was 76 percent in an Australian public hospital.

That’s not a perfect result, but it does provide a starting point before other, more invasive tests are embarked on; in conjunction with current diagnostic techniques, it could improve early diagnosis – and therefore people’s chance of survival.

The next step, the researchers said, will be to take MelDX to clinical trial, which is currently being organised, and which could help refine the test.

“We envision this taking about three years. If this is successful we would hope to be able to have a test ready for use in pathology clinics shortly afterwards,” said Melanoma Research Group head Mel Ziman.

“The ultimate goal is for this blood test to be used to provide greater diagnostic certainty prior to biopsy and for routine screening of people who are at a higher risk of melanoma, such as those with a large number of moles or those with pale skin or a family history of the disease.”

Meanwhile, there are easy ways you can help protect yourself from melanoma and other skin cancers, including wearing sunscreen, staying in the shade during the hottest hours of the day, and avoiding UV tanning beds.