New research suggests that patients may have more pain and pain-related brain activity when undergoing a painful medical procedure performed by a physician they perceive as less trustworthy

When doctors are seen as less trustworthy by their patients it can increase reported pain and pain-related brain activity, new research from the University of Miami suggests. 

In a study recently published in Cerebral Cortex and led by recent University of Miami Psychology Ph.D. graduate Steven R. Anderson, and Elizabeth Losin, assistant professor of psychology at the University of Miami, participants underwent a series of simulated painful medical procedures with different virtual doctors who appeared more or less trustworthy.

During these medical simulations, participants had their brain activity measured using functional MRI (fMRI). Researchers compared brain responses to the simulated painful medical procedure (actually painful heat stimulations on their arms) and participants’ ratings of their pain when participants were treated by more or less trustworthy appearing virtual doctors.

The doctors in the virtual medical interaction were images of individuals dressed in a doctor’s white coat with faces that were created with a computer algorithm to look more or less trustworthy.  The facial trustworthiness algorithm was previously developed by Alexander Todorov and his colleagues at Princeton University.

“The participants in our study reported increased pain when they received painful heat stimulations from the doctors they perceived as less trustworthy,” said Losin, who also leads the Social and Cultural Neuroscience lab. In addition to influencing how much pain participants reported during the fMRI scan, having the simulated painful procedure with less trusted doctors was also associated with increased brain activity in pain-related brain regions, as well as increased responses in a pain-predictive brain biomarker, the Neurologic Pain Signature.

This study was inspired by an increasing number of studies showing that patients’ trust in their doctors can affect a variety of health outcomes, including pain. These findings have far-reaching implications for understanding health disparities because many studies have also demonstrated the people from marginalized groups including people of color, lower income individuals, and women often have a low degree of trust in the health care system in general and doctors in particular.

Losin and her lab previously conducted a study using face-to-face medical simulations where they experimentally changed how much doctors and patients trusted one another by making them feel more or less culturally similar to each other. This study was published in The Journal of Pain in 2017. Researchers found that the more culturally similar patients felt to their doctors the more they trusted them and the less pain they experienced from a simulated painful diagnostic procedure.   

In the current study, they wanted to understand the brain basis of the trust-related reductions in pain they have previously observed by using functional neuroimaging. “Although we had previously found that how much you trust your doctor can influence your experience of pain, there was surprisingly little known about the brain basis for this effect,” Anderson said.

The researchers found that when patients received a simulated painful diagnostic procedure from the doctors they trusted less they reported that it was more painful (more intense) and that the pain bothered them more (more unpleasant). This was particularly true when the painful diagnostic procedure stimulus was the most intense. This means that the researchers found the same thing that they had in their 2017 study.

When examining the brain, as they predicted, the researchers found that patients had more activity in a number of pain-related brain structures when undergoing the painful diagnostic procedure analogue with a low-trust doctor compared to a high-trust doctor. 

To increase their certainty that the trust-related reductions in brain activity the researchers observed were specific to pain, they also tested a brain-based pain biomarker, the Neurologic Pain Signature. They found that Neurologic pain signature pattern was more strongly expressed when patients received the painful diagnostic procedure analogue for low trust doctors versus high trust doctors, suggesting that pain-specific patterns of brain activity are reduced by trusting your doctor.

Finally, the authors wanted to understand what real-world factors might be leading people to feel more pain and have more pain-related brain activity when they trust their doctors less. To answer this question, they examined whether participants’ mistrust in health care organizations was associated with increased neural responses to the painful diagnostic procedure analogue. The team found that the more mistrust in medical organizations participants had, the more brain activity they had in brain regions involved in pain, attention, and emotion when experiencing and evaluating pain. Importantly, these findings suggest that the trust-related reductions in pain the researchers observed in the lab may extend to real-world medical care.

“The takeaway from this study is not necessarily that we need to train doctors to make different facial expressions. Rather, our results demonstrate that even small changes to the doctor-patient relationship may be enough to decrease patients’ pain,” Anderson noted.

Anderson further added that the results of this study “make clear that even non-verbal aspects of the doctor-patient relationship make a difference in the patient’s pain, which can inform interventions aimed at reducing patient pain and pain disparities.”

Every meal you sit down to makes an impression, with foods filed away as something delicious to be sought out again, or to be avoided in disgust if we associate the flavor with gut malaise.

How this decision is made turns out to be so fundamental to our wellbeing—determining what foods to seek and avoid—that the signals are coordinated within the most primitive parts of our brains, the brain stem or hindbrain. This brain region also helps us decide when we are “full” and should stop eating.

To date, scientists interested in how and why people gain weight and the diseases that can result from overeating and obesity have focused on a part of the brain called the hypothalamus, following discoveries of two intertwined systems that play important roles in controlling energy balance, the leptin and melanocortin systems.

A paper in the journal Nature Metabolism looks outside this brain region and reviews the various brain pathways that meet in the brain stem to control feeding behavior, using a technique that offers an unbiased look at the neurons involved.

“Everything the hypothalamus does ends up converging in the brainstem. The brain stem is super important in the control of feeding because it takes all sorts of information from your gut, including whether the stomach is distended and whether nutrients have been ingested, and integrates this with information from the hypothalamus about nutritional needs before passing it all on to the rhythmic pattern generators that control food intake,” said Martin Myers, Jr., M.D., Ph.D., professor of internal medicine and Molecular & Integrative Physiology and director of the Elizabeth Weiser Caswell Diabetes Institute.

The recent review builds on recent findings in mice from the Myers lab that revealed the existence of two different food intake-suppressing brain stem circuits– one that causes nausea and disgust, and one that does not, as well as from collaborations with colleague Tune Pers, Ph.D., of the University of Copenhagen. Pers and his group used single cell mapping of brain cells within the dorsal vagal complex, a region in the brain stem that mediates a host of unconscious processes, including feelings of satiety (or sickness) after eating.

The new review paper, from first author Wenwen Cheng, Ph.D., Myers, Pers, and their colleagues, integrates these findings with other recent discoveries to build a new model of brainstem neuronal circuits and how they control food intake and nausea.

“Taking all of this information together allows us to predict which set of neurons control this or that function,” said Myers.

He notes that many of these cell populations are targets for new and effective anti-obesity drugs— for example, a class of drugs for diabetes called GLP1 receptor agonists that can lower blood sugar and help you eat less.

“There is a population of GLP1 neurons in the brain stem which, if you turn them on, will stop food intake but cause violent illness, but there may be another population of neurons that stops eating without making you feel badly.”

Having a detailed map of these neurons and understanding the effects of modifying these cell targets, Myers explains, can assist in making drugs with fewer negative side effects.

Finding treatments for advanced multiple sclerosis (MS) has been difficult. But new research may help neurologists identify which drugs are best for people with the advanced form of MS called secondary progressive MS. The new study, published in the June 30, 2021, online issue of Neurology^®, the medical journal of the American Academy of Neurology, found that the more potent disease-modifying drugs are more effective in reducing flare-ups in secondary progressive MS than the less potent drugs that tend to be safer to take. However, the researchers found no difference in how fast the disease progressed between these two types of drugs.

Most people with MS are initially diagnosed with relapsing-remitting MS, marked by symptom flare-ups called relapses followed by quiet periods called remission. More than half of these people eventually transition to secondary progressive MS, which is a slow, steady, worsening of the disease that may or may not include relapses.

“Multiple sclerosis is a complicated disease to treat and must be closely monitored as it is managed with various medications, some of which can have serious side effects,” said study author Tomas Kalincik, MD, PhD, of the University of Melbourne in Australia. “High-efficacy medications are prescribed in early multiple sclerosis to more aggressively treat the disease and have been found to more effectively prevent flare-ups and modify progression, but less is known about how effective these therapies may be later when relapsing-remitting MS transitions to secondary progressive MS.”

The study involved 1,000 people with secondary progressive MS. Participants were followed for 10 years to see whether they had relapses and if they became more disabled over time.

Researchers divided participants into two groups, those treated with one of the more potent drugs, or high-efficacy drugs (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine and fingolimod) and those treated with one of the less potent drugs, or low-efficacy drugs (interferon β, glatiramer acetate and teriflunomide). People in each group were matched for factors like disability level and how long they had secondary progressive MS.

After accounting for the lag time before a person starts to experience the benefit of a medication, researchers found that in people with active disease, or those experiencing relapses within the past two years, people who were treated with high-efficacy medications experienced 30% fewer relapses than people treated with low-efficacy medications. People in the high-efficacy group experienced an average of 0.17 relapses per year compared 0.27 relapses per year in the low-efficacy group.

“Our study finding that high-efficacy therapies are superior to low-efficacy therapies only in reducing relapses in people with active secondary progressive MS provides valuable guidance for neurologists when choosing the most effective therapies for people with this form of MS,” said Kalincik. “When the goal is to alleviate ongoing relapse activity, more potent therapy is justified. But when the goal is to limit disability progression in secondary progressive MS, both types of drugs show comparable effectiveness.”

A limitation of the study was that participants were grouped by those taking high-efficacy or low-efficacy therapies. However, therapies were not studied individually. Kalincik said it is possible that individual therapies may have different effects on symptoms and disability and recommend that they be examined separately in future research.

Caregivers with their own disabilities face a litany of complications while trying to tend to aging or ailing spouses and partners: health problems, mental health difficulties, work issues, even financial and healthcare strains, according to the inaugural white paper from a University of Pittsburgh center studying caregiving.

While caregiver issues abound across all groups of Americans today, “NCFS Caregiver Profiles: A Closer Look at Spousal Caregivers” analyzes recent data from two large national datasets to provide a detailed look at caregivers who are supporting a spouse or partner and identifies unmet needs for support among younger caregivers with disabilities.

In fact, this data dive from the Pitt National Rehabilitation Research & Training Center on Family Supports (NCFS) found that 20% of all spousal caregivers with disabilities under the age of 65 live below the poverty line — compared to 7.6% of their counterparts over 65. More than 1 in 4 of the under-65 caregivers with a disability reported challenges to accessing a doctor due to cost as well. Under-65 spousal caregivers with a disability also were about half as likely as those without disabilities in the same age cohort to be employed for wages (32% vs. 60%), were less likely to be self-employed (5% vs. 10%) and were less likely to have a four-year college degree (12% vs. 27%). At 49%, this under-65 caregiver cohort with disabilities also was the most likely to report a diagnosis of depressive disorder, compared to only 17% of those in the same age group without disability and 25% of those over-65 with disability.

“These findings indicate a potential gap in services for younger caregivers with disability and a need to focus on  this population for support,” said Everette James, JD, MBA, Director of Pitt’s Health Policy Institute and M. Allen Pond Professor of Health Policy and Management at the School of Public Health.

The NCFS spousal caregiver brief is the first in a series of reports intended to inform public policy and practice around the role of family caregivers — with a focus on understudied populations. The new report highlights some of the unique characteristics and challenges faced by spousal caregivers compared to other types of caregivers, such as adult children tending to aging parents.

Spousal caregivers were more likely to report a disability and were generally older than other caregiver subgroups, with close to half of the population studied over the age of 65. Spousal caregivers also had higher burdens of chronic disease and often reported worse physical health, even leading to issues at work.

However, the data for under-65 caregivers is lacking, the researchers found.

“Due to the way that individuals are sampled for data collection, not all age groups are represented across all data sets, meaning that some information is only available for older care recipient and caregiver pairs,” said Scott Beach, PhD, Co-Director of NCFS and Interim Director of the University Center for Social and Urban Research.

Pitt researchers combed data from the Behavioral Risk Factor Surveillance System and the National Health and Aging Trends Study National Study of Caregiving, studying populations both younger and older than 65, and with or without a disability. Among their findings:

• Nearly half of all spouse caregivers are over 65 (47%, with another 39% between ages 45-64); adult children caregivers over 65 comprise only 8% of their group.
• When comparing chronic disease among all caregivers – tending for child, parent, other relative, non-relative or spouse – the spouse caregivers had the highest prevalence of many issues: obesity/overweight (71.1%), high blood pressure (51.4%), high cholesterol (50.2%), arthritis/gout/lupus/fibromyalgia (48.2%), diabetes (18.8%), skin cancer (13.3%) or other type of cancer (13.7%). When the data is categorized by age and the presence of disability, spousal caregivers over age 65 with disabilities have the highest burden of many chronic diseases.
• The gulf when it came to work was wide: 8% of those with disabilities caring for a spouse age 65 or older said caregiving made work harder and 6.5% missed work due to caregiving, compared to 2% in each category of those without disabilities.
• Indicators of caregiver burden were high for spousal caregivers with disabilities: spousal caregivers with disability were approximately twice as likely to meet the criteria for risk of anxiety or depression and to report financial, physical and emotional difficulties providing assistance to their spouse or partner, compared to those without disabilities.
• The majority of caregivers with a disability said they received training following the hospitalization of their spouse or partner, and they were more likely to use assistance such as paid care, respite services and support groups. Still, utilization of such support services was relatively low – less than 10% of caregivers with or without disabilities.

“In the future, we plan to continue to explore national data on caregivers, and look for insights into understudied populations,” said Meredith Hughes, JD, MPH, Senior Policy Analyst at HPI and Visiting Assistant Professor in the School of Public Health.