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.

Study: Aerobic Exercise Has Antidepressant Effects for Those With Major Depression

It seems like doctors should prescribe this sort of moderate intensity aerobic exercise instead of pharmaceutical drugs much more.

An analysis of randomized controlled clinical trials indicates that supervised aerobic exercise has large antidepressant treatment effects for patients with major depression. The systematic review and meta-analysis is published in Depression and Anxiety.

Across 11 eligible trials involving 455 adult patients (18-65 years old) with major depression as a primary disorder, supervised aerobic exercise was performed on average for 45 minutes, at moderate intensity, 3 times per week, and for 9.2 weeks. It showed a significantly large overall antidepressant effect compared with antidepressant medication and/or psychological therapies.

Also, aerobic exercise revealed moderate-to-large antidepressant effects among trials with lower risk of bias, as well as large antidepressant effects among trials with short-term interventions (up to 4 weeks) and trials involving preferences for exercise.

Subgroup analyses revealed comparable effects for aerobic exercise across various settings and delivery formats, and in both outpatients and inpatients regardless of symptom severity.

“Collectively, this study has found that supervised aerobic exercise can significantly support major depression treatment in mental health services,” said lead author Dr. Ioannis D. Morres, of the University of Thessaly, in Greece.

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.

Mental Health Diagnoses Among U.S. Children and Youth Continue to Rise at Alarming Rates

It follows the trend of mental health disorder rates rising globally. This isn’t progress — it shows that, whatever the newest low unemployment numbers in the “booming” economy are, there is an undercurrent of something gone seriously wrong in our societies.

The number of children and adolescents visiting the nation’s emergency departments due to mental health concerns continued to rise at an alarming rate from 2012 through 2016, with mental health diagnoses for non-Latino blacks outpacing such diagnoses among youth of other racial/ethnic groups, according to a retrospective cross-sectional study presented during the American Academy of Pediatrics National Conference & Exhibition.

“Access to mental health services among children can be difficult, and data suggest that it can be even more challenging for minority children compared with non-minority youths,” says Monika K. Goyal, M.D., MSCE, assistant division chief and director of research in the Division of Emergency Medicine at Children’s National Health System and the study’s senior author. “Our findings underscore the importance of improving access to outpatient mental health resources as well as expanding capacity within the nation’s emergency departments to respond to this unmet need.”

An estimated 17.1 million U.S. children are affected by a psychiatric disorder, making mental health disorders among the most common pediatric illnesses. Roughly 2 to 5 percent of all emergency department visits by children are related to mental health concerns. The research team hypothesized that within that group, there might be higher numbers of minority children visiting emergency departments seeking mental health services.

To investigate this hypothesis, they examined Pediatric Health Information System data, which aggregates deidentified information from patient encounters at more than 45 children’s hospitals around the nation. Their analyses showed that in 2012, 50.4 emergency department visits per 100,000 children were for mental health-related concerns. By 2016, that figure had grown to 78.5 emergency department visits per 100,000 children.

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.”

Mental Health Disorder Rates Rising Globally

This is a sign of regression or stagnation, not progress, and it suggests that there needs to be a shift in the general direction human societies are on. Outside of the economic impacts of lost productivity, there are many collateral effects (e.g., worsened interpersonal relationships) that are associated with widespread mental health problems continuing as well.

The “Lancet Commission” report by 28 global specialists in psychiatry, public health and neuroscience, as well as mental health patients and advocacy groups, said the growing crisis could cause lasting harm to people, communities and economies worldwide.

While some of the costs will be the direct costs of healthcare and medicines or other therapies, most are indirect – in the form of loss of productivity, and spending on social welfare, education and law and order, the report’s co-lead author Vikram Patel said.

The wide-ranging report did not give the breakdown of the potential $16 trillion economic impact it estimated by 2030.

“The situation is extremely bleak,” Patel, a professor at Harvard Medical School in the United States, told reporters.

He said the burden of mental illness had risen “dramatically” worldwide in the past 25 years, partly due to societies ageing and more children surviving into adolescence, yet “no country is investing enough” to tackle the problem.

“No other health condition in humankind has been neglected as much as mental health has,” Patel said.

The World Health Organization (WHO) estimates that around 300 million people worldwide have depression and 50 million have dementia. Schizophrenia is estimated to affect 23 million people, and bipolar disorder around 60 million.

The Lancet report found that in many countries, people with common mental disorders such as depression, anxiety and schizophrenia routinely suffer gross human rights violations – including shackling, torture and imprisonment.

Richard Horton, editor-in-chief of the medical journal the Lancet, which commissioned the report, said it highlighted the “shameful and shocking treatment of people with mental ill health around the world”.

It called for a human rights-based approach to ensure that people with mental health conditions are not denied fundamental human rights, including access to employment, education and other core life experiences.

Statistics on the Undercurrent Societal Problem of Loneliness

Now there is evidence that loneliness itself is directly harmful to human health, and that’s not to mention the indirect damage it causes. How UK doctors are prescribing people social activities also seems like a refreshingly progressive way at combating the problem.

Everyone feels isolated sometimes, but with one in five Americans chronically lonely, has loneliness reached epidemic proportions? In 1988, the journal Science published a landmark study suggesting isolation was as strong a risk factor for morbidity and mortality as sedentary lifestyle, high blood pressure and smoking or obesity. Since then, loneliness has become an increasing public health concern and health officials are now taking the idea of an epidemic seriously. As the population ages, the burden of social isolation on public health will only increase.

Loneliness is one aspect of interrelated conditions such as isolation due to illness, disability or age; the social and language-based isolation of being an immigrant; depression; poverty; discrimination, etc.

This past summer, two surveys made news, marking the extent of loneliness in the U.S. and other economically developed countries. Since these and other studies are new, we can anticipate learning more about the interrelationships of factors that contribute to loneliness over time. That shouldn’t stop us from addressing the problem now, but may help provide better perspective.

The most recent survey, from The Economist and the Kaiser Family Foundation, finds that 9 percent of adults in Japan, 22 percent in America and 23 percent in Britain “always” or “often” feel lonely or lack companionship. Another study of 20,000 U.S. adults, 18 and older, published in May by Cigna and market research firm Ipsos, reveals nearly half of American adults reported “sometimes” or “always” feeling alone (46 percent) or left out (47 percent); more than one in four Americans (27 percent) “rarely” or “never” feel that people understand them; and 43 percent of Americans “sometimes” or “always” feel their relationships lack meaning and they are isolated. One finding stands out: Generation Z (22 years and younger) scored the lowest of every age-group and appears to be more prone to experiencing significant loneliness. Gen Z may be the loneliest generation.

Regarding health impacts, several recent studies have found that loneliness is a risk factor for decreased resistance to infection, cognitive decline and conditions such as depression and dementia.

A UC San Francisco 2010 study found loneliness to be a predictor of functional decline and death among adults 60 and older. Over six years, lonely subjects were more likely to experience decline in activities of daily living (24.8 percent vs. 12.5 percent); develop difficulties with upper extremity tasks (41.5 percent vs. 28.3 percent); experience decline in mobility (38.1 percent vs. 29.4 percent) or climbing (40.8 percent vs. 27.9 percent); and face increased risk of death (22.8 percent vs. 14.2 percent). It appears that without social interaction, we languish and decline, though it’s possible that greater longevity, coupled with functional decline, leads to social isolation.

At the other end of the spectrum are challenges faced by young adults. Two 2017 national surveys of adolescents, in grades eight to 12, found among lonely individuals, especially females, depressive symptoms and suicide rates increased between 2010 and 2015. The studies found adolescents who spent more time on social media and devices such as smartphones more likely to report mental health issues, though it’s not clear if the self-directed isolation of screen time leads to or results from loneliness.

While we need to know more about causes to stanch this epidemic, many studies identify ways to minimize the effect of loneliness. Socializing with friends and family and increasing meaningful face-to-face interactions decreases loneliness. Those with active social lives report better health. Strong social affiliations — such as being part of a religious group, hobbyist circle or exercise group — have positive effects. Doctors in the United Kingdom make “social prescriptions,” specifying patients take part in structured social activity.