Magic Mushrooms May Relieve Chronic Pain and Depression

By Crystal Lindell

A new study shows that psilocybin, the active ingredient in what’s colloquially called magic mushrooms, could help relieve chronic pain and depression by targeting specific parts of the brain — at least in mice.

Psilocybin is a naturally occurring alkaloid with psychoactive properties that’s been used for pain relief for thousands of years. In the United States, however, it is classified as an illegal Schedule One controlled substance. 

Researchers at the Perelman School of Medicine at the University of Pennsylvania tested psilocybin on laboratory mice with chronic nerve injury and inflammatory pain.

They found that a single dose reduced both pain, anxiety and depression in the mice, judging by their behavior. The benefits lasted almost two weeks.

Unlike many pharmaceuticals, researchers say psilocybin gently activates specific nerves in the brain, called serotonin receptors.

“Unlike other drugs that fully turn these signals on or off, psilocybin acts more like a dimmer switch, turning it to just the right level,” lead author Joseph Cichon, MD, an assistant professor of Anesthesiology and Critical Care at Penn, said in a press release.

”This new study offers hope. These findings open the door to developing new, non-opioid, non-addictive therapies as psilocybin and related psychedelics are not considered addictive.”

To pinpoint where the effects originated, researchers injected psilocin — the active metabolite that the body rapidly converts from psilocybin — into different parts of the mice’s central nervous system. The team then used advanced fluorescent microscopy, a technique that uses glowing dyes to detect nerve activity, to see which neurons are activated and firing.

When psilocin was injected directly into the prefrontal cortex of the brains of the mice, it provided the same pain relief and mood improvements as when psilocybin was given to the whole body. But when researchers injected psilocin into the spinal cords of the mice, they found that it didn’t have the same calming effect.

“Psilocybin may offer meaningful relief for patients by bypassing the site of injury altogether and instead modulating brain circuits that process pain, while lifting the ones that help you feel better, giving you relief from both pain and low mood at the same time,” said Cichon.

Researchers hope their findings, published in the journal Nature Neuroscience, could help spur advancements in treatments for other conditions, such as addiction or post-traumatic stress disorder.

Cichon says more research is needed to determine the effectiveness of psilocybin.

“In my anesthesiology practice, I often see that both pain and mood symptoms can worsen following surgery due to the physiological and psychological stress imposed by the procedure,” he said. “While psilocybin shows promise as a treatment for both pain and depression, it remains uncertain whether such therapies would be safe, effective, or feasible in the context of surgery and anesthesia.”

The Penn team plans further studies to investigate dosing strategies, long-term effects, and the ability of the brain to re-wire itself through the use of psilocybin.

“While these findings are encouraging, we don’t know how long-lived psilocybin’s effects are or how multiple doses might be needed to adjust brain pathways involved in chronic pain for a longer lasting solution,” said co-author Stephen Wisser, a PhD student in Cichon’s lab.

While the DEA considers psilocybin an illegal substance with no accepted medical use, Oregon and Colorado have legalized it for supervised therapeutic use. Several cities in California, Michigan, Minnesota, Washington and Maine have also decriminalized it. And efforts are underway to change psilocybin’s federal status. 

The Food and Drug Administration has granted a breakthrough therapy designation to psilocybin to expedite research and drug development. Over 60 scientific studies have shown the ability of psilocybin and other psychedelics to reduce pain from fibromyalgia, cluster headache, complex regional pain syndrome (CRPS) and other conditions.

How Much Is Your Pain Worth?

By Crystal Lindell

How much pain would you be willing to endure if someone paid you?

That’s the question an international team of researchers posed in an unusual new study looking for an alternative to the 1-10 pain scale.

In a series of experiments, they offered 330 healthy volunteers in Switzerland money to undergo mild electric shocks, heat pain or no pain at all. Someone opting for a painful stimulus was paid about $20, while those who opted for having no pain received only $10.

The idea behind putting a price on pain was to see if the responses would be a better way to measure pain than the subjective and much criticized pain scale, which has been used for decades to have patients self-evaluate their pain levels.

“We’ve all been asked to rate our pain from one to ten—but one person’s three might be another’s five, and those numbers can shift with experience. Our research proposes a better way: turning pain into money — not to commodify suffering, but to create a scale we can all share,” explained lead author Carlos Alós-Ferrer, PhD, a Professor of Economics at Lancaster University Management School in the UK. 

The study findings, published in the journal Social Science & Medicine, suggest that people’s willingness to accept money in exchange for pain is a more reliable way to measure discomfort than self-reported methods.

Researchers say their economic incentives “greatly outperformed” traditional pain scales. It helped them distinguish more clearly between different levels of pain; detect the effects of pain relief more consistently; and allowed for more meaningful comparisons between people.

Interestingly, no participant chose to avoid pain completely. Everyone had a price for pain if it was high enough.  

Different people put different prices on the same pain, but they had an easier time rating their pain than they did when using the 1-10 pain scale.

“As a result, measurements are more precise and the shift from low to high levels of pain is clearly reflected in the monetary scale,” Alós-Ferrer said. “This makes it useful for clinical trials to study the effectiveness of painkillers and treatments, because participants are randomly assigned to different groups.”

I believe if a money-incentivized pain scale is used only for research studies, it might be useful. Afterall, there is definitely a need for more accurate pain measurements in research, as well as treatment.

However, my concern is that it could be misused in a clinical setting, just like the pain scale is. Researchers said “inaccurate pain measurements can lead to inadequate pain management,” and pointed to emergency medical situations and quality of life issues for people with chronic pain.

However, in most cases, the reason pain is not adequately treated has nothing to do with the pain scale. It’s because doctors tend to dismiss people’s pain and then withhold one of the most effective treatments: opioids.

I’ve written before about why I don’t like the 1-10 pain scale, which doctors tend to ignore even if you say your pain is a 10. But I don’t think replacing it with a question about how much money you’d need to endure more pain is the answer.

Rather, the best solution I’ve seen from a patient perspective — at least when it comes to chronic pain — is a scale that asks how pain is impacting daily life activities, known as the Quality of Life Scale, (QOLS).

It's a reverse of the traditional pain scale, in that 0 is the worst pain, while 10 means you're doing pretty well.

It features descriptions like:

0: Stay in bed all day. Feel hopeless and helpless about life.

1: Stay in bed at least half the day. Have no contact with the outside world.

All the way up to:

10: Go to work/volunteer each day. Normal daily activities each day. Have a social life outside of work. Take an active part in family life.

While QOLS probably isn’t ideal for studies on acute pain, it is a great way to communicate pain levels between patient and doctor. In fact, I’d say it’s significantly better than trying to assign a monetary value to pain.

Because as anyone with severe chronic pain will tell you, there’s not enough money in the world to make me want to endure my pain even one second longer than I need to.

Many Older Adults With Chronic Pain and Poor Health Can Regain Wellness

By Pat Anson

“You’re not getting older, you’re getting better.”

There’s some truth behind that cliché about growing old, according a novel study in Canada that found many older adults in poor health -- due to chronic pain and other chronic conditions -- can fully recover within just a few years.

“This isn’t just a story of resilience — it’s a roadmap for how we can help more older adults recover and thrive,” says first author Mabel Ho, PhD, a researcher at the Factor-Inwentash Faculty of Social Work at the University of Toronto. “Our findings highlight the powerful role of modifiable lifestyle and psychosocial factors in shaping healthy aging trajectories.”

Ho and her colleagues followed 8,332 respondents who were 60 years of age or older and in poor physical or mental health. Nearly one in five (18.7%) had chronic pain so severe it was considered disabling, while others had chronic illnesses such as diabetes, heart disease, hypertension, arthritis and osteoporosis.

Not surprisingly, many of the participants also felt depressed, unhappy, slept poorly, and led isolated lives with few social connections.

Their baseline health status at the start of the study was then compared to their physical and mental health after 3 years, to assess whether they had achieved “optimal well-being” – meaning they had no disabling pain, discomfort or limitations on daily activities, as well as good mental health, happiness and life satisfaction.

The research findings, published in PLOS One, show that nearly one in four older adults regained optimal well-being within just three years.

The researchers then sought to identify what factors increased the likelihood that older adults could recover their physical and mental health. Those who reported strong psychological and emotional wellness at the outset of the study were over five times more likely to achieve the high bar of “optimal well-being” when compared to those who struggled with their mental health.

Other factors significantly associated with recovery include a healthy body weight, regular physical activity, good sleep, not smoking, and participating in social activities.

“It’s incredibly encouraging to see that with the right supports and lifestyle, many older adults can reclaim full health, happiness, and independence -- even after serious health challenges,” says Ho.

The study suggests that age-related policies and programs should prioritize physical and mental wellness, to help show that recovery is not only possible for older adults, but common.

“Too often, the focus in aging research and geriatric practice is on decline and disability,” says senior author Esme Fuller-Thomson, PhD, Director of the Institute for Life Course & Aging at the University of Toronto. “Our findings disrupt that narrative. Older adults can and do bounce back—and we need to build systems that support recovery.”

By the end of the study, over 19% of those who had chronic disabling pain had achieved optimal well-being, while nearly 10% of those whose daily activities were limited progressed to no limitations. Over 12% of those who rated their physical health as poor to fair at the start of the study achieved a full recovery.   

Other factors strongly associated with optimal well being were higher education, home ownership, higher income, marriage, and having someone to show love and affection.

“We want this study to reshape how society views aging,” added Ho. “With the right environment, resources, and supports, older adults don’t just survive after struggling with health or well-being issues— they thrive.”

The study did not evaluate what medications or therapies helped older adults recover their health.

Childhood Trauma Raises Risk of Chronic Pain and Other Health Problems in Adults

By Crystal Lindell

A new study has found links between childhood trauma, chronic pain and several health problems in adults, according to research published in JAMA Network Open. 

Many previous studies have found that adverse childhood experiences (ACEs) increase the risk of chronic pain in adulthood. This study goes further, finding links between ACEs and severe pain, poor mental health, back and hearing problems, gastrointestinal issues, and hypertension at age 50.

However, it remains unclear how much of that association may be causation and how much is simple correlation. There is also a very real concern that the study will add to the stigma that chronic pain patients already face in the medical community. 

The research, which was conducted by a team of scientists at the University of Aberdeen, followed over 16,000 participants in the UK who were enrolled in the National Child Development Study.  All were born during one week in 1958 in England, Scotland or Wales, and were interviewed when they turned 50.

Researchers asked about their current health and whether they experienced any childhood trauma, such as abuse, neglect, bullying, divorce and financial stress, or if they had witnessed substance abuse, criminal activity or mental illness in their family.

While most studies report associations between ACEs and a single health outcome, researchers say this is the first research to look at a broad range of health outcomes.

They found that mental health problems and severe pain in adults had the strongest connections to childhood trauma. Men and women who experienced childhood adversity were more likely to suffer from depression, anxiety, and chronic pain at 50. 

Women who had an ACE were also more likely to have digestive problems, asthma or bronchitis compared to women who did not experience childhood trauma.

It’s important to note that the “higher risk” was often marginal, at best. For example, while 8.7% of men who experienced childhood trauma had severe pain at 50, that compares to 4.88% of men with severe pain at 50 who did not have an ACE. That’s just a 4% difference.

The same is true for women. Researchers found that 11.22% of women with childhood trauma had severe pain at 50, compared to 7.53% of women with no history of ACE. Again, just a 4% difference. Most researchers look for at least a 5% difference before calling an outcome “statistically significant.”

Little or no association was found between ACEs and migraine, hay fever or rhinitis, eyesight problems, or skin problems. 

Researchers found that the more trauma experienced, the greater the impact on health at age 50. People who experienced four or more types of childhood adversity had the highest risk of developing health problems as adults. Abuse, neglect, and family conflict had the most wide-ranging consequences. Just one adverse childhood event was found to increase the risk of dying before age 50.

The research was partly funded by Versus Arthritis, the UK’s largest charity supporting people with arthritis.

"This important research highlights the strong relationship between early childhood adversity and severe pain in adulthood. Findings suggest that our earliest experiences may be driving the health inequalities we know exist for people living with chronic pain,” Deborah Alsina, CEO of Versus Arthritis, said in a press release.

"Tackling childhood adversity is vital if our governments are serious about reducing the burden of chronic pain for the next generation."

Early Intervention and Prevention

Researchers say the study highlights the importance of preventing childhood trauma and providing early support to at-risk families.

"Going forward, screening for ACEs in primary care settings, and targeted interventions for at-risk individuals, may help reduce the burden of chronic pain, mental ill-health, and other poor health outcomes,” said lead author Gary Macfarlane, PhD, Chair of Epidemiology at the University of Aberdeen.

"While 'broad spectrum' interventions remain important to ameliorate the impact of ACEs, a targeted approach, considering types of ACE, could address specific vulnerabilities — particularly mental ill-health and severe pain.”

That’s an important goal, but for adults already suffering from health issues that could be linked to childhood trauma, that doesn’t offer much help. 

In the real world, studies like this are very often used to dismiss the health problems people suffer. That's especially true for chronic pain. 

Patients are often told their pain was caused by childhood trauma, and doctors use that as an excuse to invalidate their symptoms and withhold treatments like opioid pain medication. This gets especially frustrating when a history of childhood trauma is then used to claim that a patient is more likely to abuse opioids. 

Many doctors seem to believe that if childhood trauma is the direct cause of a health issue, then the only real treatment is mental health services. This can contribute to the stereotype that chronic pain is “all in your head” or that patients are “just looking for attention.”

There is also the question of causation vs correlation. For example, many health conditions are hereditary, including those that cause chronic pain, like arthritis and Ehlers-Danlos Syndrome.

Parents who grew up with those health problems may be more likely to have negative experiences with their children. Chronic pain drains time, money and energy, which then impacts someone's ability to be a present parent. So a parent with chronic pain may be more likely to neglect their child, not out of malice but out of necessity, as they deal with their own health issues. 

Then when the child grows up and has chronic pain, it seems like it could be related to childhood trauma when it may be actually be a case of simple genetics. 

While it is important to find better ways to respond to children who have experienced trauma, it’s also important that such research is not used to dismiss adults dealing with health issues. For many adults, the current trauma of living with chronic pain is more pressing than what they experienced in childhood. 

Chronic Pain Surged in U.S. After Pandemic

By Pat Anson

Rates of chronic pain and disabling pain surged in the United States after the Covid pandemic, reaching the highest levels ever recorded, according to a new study.

In 2019, about 20.5% of Americans (50 million people) had chronic pain and 7.5% had high-impact pain, which is pain strong enough to limit daily life and work activity.

Pain prevalence remained stable during the pandemic, and by some measures even declined, but in 2023 the chronic pain rate surged to 24.3% of Americans, while high-impact pain rose to 8.9% of the population.

That brought the total number of people who have chronic pain to 60 million, with 21 million having high-impact pain.

“We found that chronic pain, already a widespread health problem, reached an all-time high prevalence in the post-pandemic era, necessitating urgent attention and interventions to address and alleviate this growing health crisis,” wrote co-authors Anna Zajacova, PhD, at Western University in Ontario and Hanna Grol-Prokopczyk, PhD, at the University of Buffalo..

The study is based on results from the 2019, 2021 and 2023 National Health Interview Surveys (NHIS), a federal survey conducted every two years. A preprint of the study was released last year and has now been published in the peer-reviewed journal PAIN.

The 2023 surge in pain was observed in all age, gender, racial/ethnic groups, education levels, and in both rural and urban areas.

Pain increased in almost all body areas, including the back and neck; arms, shoulders and hands; hip, knees and feet; headache or migraine; and in the abdominal, pelvic, and genital areas. The lone area where pain declined was in the jaw or teeth.

Why did pain increase after the pandemic, but not during the pandemic — when people saw doctors less often and postponed or cancelled many health procedures?

One possible explanation is that Covid relief payments, expanded unemployment benefits, and eviction moratoriums eased financial stress.

Working from home and commuting less also lessened physical demands, while giving remote workers more opportunities for self-care.

PAIN journal

“The big question is why we saw this substantial increase in pain prevalence after the pandemic. We examined the role of long COVID and found that it explained about 13% of the increase,” said Grol-Prokopczyk. “None of the other measures we examined — including changes in income or physical health conditions — explained the increase.

“We speculate that abrupt termination of pandemic-era policies, such as remote work arrangements and expanded unemployment benefits, may have played a role.”

In addition to long Covid, researchers also noted an uptick in rates of health conditions that can cause pain, such as arthritis, cancer, cardiovascular disease, diabetes, depression, and anxiety.

The finding of an increase in pain rates conflicts with an FDA analysis that predicted the “medical need” for hydrocodone, oxycodone and other pain relieving Schedule II opioids would decline by 5.3% in 2023. The FDA also predicted a 7.4% decline in the medical use of opioids in 2024 and a 6.6% decline in 2025.

Those FDA projections are important because they are used by the DEA to establish annual production quotas for opioids, which have fallen for nine consecutive years. Since 2015, the DEA has reduced the supply of oxycodone by 68% and hydrocodone by 73%.

When short-term, acute pain is poorly treated, it can have long-term consequences for patients who may transition to chronic pain. Healthcare visits for non–Covid health issues declined dramatically in 2020 and 2021, particularly at hospitals and emergency departments, which are often the first site of care for acute pain management.

Researchers say the lack of adequate and timely pain management during the pandemic may have contributed to more people having chronic pain and high-impact pain in 2023.

“These findings highlight the importance of expanded epidemiological and clinical research on chronic pain to better understand population-level drivers of pain, and to improve national pain prevention and treatment efforts for the many Americans at risk of or affected by pain,” said Grol-Prokopczyk.

Brains Control Pain Differently, Depending Where It’s Felt

By Crystal Lindell

Different parts of the brain are more active when relieving pain — depending on where the pain originates — according to a new Australian study. The finding could lead to more targeted and effective treatments that utilize the body’s own pain relief system.  

Researchers  at the University of Sydney made the discovery while studying the placebo effect. They used MRI brain scans to monitor 93 healthy participants, while exposing them to painful heat on various parts of the face, forearm and leg. 

Before the test, participants were given a placebo analgesic cream and told it would help relieve their pain. In reality, the “lidocaine” cream was a placebo and researchers secretly lowered the temperature of the heat, tricking the participants to believe the cream was easing their pain. 

The heat stimulus was applied to the placebo-treated area, as well as a separate untreated area for comparison. Up to 61% of participants reported less pain in the area where the cream was applied, typical of a placebo response.

The MRI scans showed how the brain responded to the placebo effect. Researchers found that upper parts of the brainstem were more active when relieving facial pain, while lower regions of the brainstem were engaged for arm or leg pain. 

“This is the first time we’ve seen such a precise and detailed pain map in the human brainstem, showing us that it tailors pain relief to the specific part of the body that’s experiencing it,” lead author Lewis Crawford, PhD, a Research Fellow at the University of Sydney, said in a press release. 

Understanding which brainstem areas are linked to different parts of the body may open new avenues for developing non-invasive therapies that reduce pain.   

“The brain’s natural pain relief system is more nuanced than we thought,” said Crawford. “Essentially, it has a built-in system to control pain in specific areas. It’s not just turning pain off everywhere; but working in a highly coordinated, anatomically precise system.”     

“We now have a blueprint for how the brain controls pain in a spatially organised way,” said senior author Luke Henderson, PhD, a Professor in the School of Medical Sciences and the Brain and Mind Centre. “This could help us design more effective and personalised treatments, especially for people with chronic pain in a specific area of their body.”

It is important to note that none of the “healthy” participants had chronic pain, and thus these results may only apply to short-term, acute pain that is treated with a placebo.

Nevertheless, the study challenges long-held assumptions about how pain relief works. Instead of relying on medications that target opioid pain receptors in the brain, researchers say receptors in the brainstem could be targeted with cannabinoids. 

“Opioid-based pain relief typically activates central areas of the brain and can affect the whole body, whereas the cannabinoid circuit that we identified appears to operate in more targeted regions of the brainstem,” said Crawford. “This supports the idea that cannabinoids may play a role in localised, non-opioid pain control.”

Most oral pain medications today – including acetaminophen, ibuprofen and opioids – work by telling the brain to relieve pain throughout the entire body. This research opens the door to more targeted therapies that relieve pain in specific parts of the body.

When Headlines Lie: Misleading News About Opioids and Chronic Pain

By Neen Monty

The headline in Physician’s Weekly screams alarm:

“Rising Use of Potent Opioids in Chronic Pain Management”

And then the sub heading:

“Long-term opioid use for chronic pain doubled, with potent opioids rising, underscoring the need for stronger guideline adoption”

Terrifying, right? We must do something!

But now, read the article. It’s based on a study recently published in the European Journal of Pain on the prevalence of long-term opioid therapy (LTOT) when treating patients with chronic non-cancer pain.

The Dutch study looked at opioid use over a ten-year period, from 2013 to 2022, using a large dataset drawn from primary care records in the Rotterdam region. This database covered more than half a million patients and included data from over 240 general practitioners.

The researchers focused on adults aged 18 and over who had been prescribed opioids continuously for at least three months. They tracked how common LTOT was over time, and also explored which diagnoses, co-existing conditions, and other medications were associated with it. They reported their findings using basic descriptive stats and calculated LTOT prevalence per 100 patient-years to show trends over the decade.

And what did they find?

“The prevalence of LTOT increased twofold from 0.54% (95% CI: 0.51–0.58) per 100 patient years in 2013 to 1.04% (95% CI: 1.00–1.07) in 2022. The proportion of LTOT episodes solely involving potent opioids slightly increased between 2013 and 2022”

In plain English, the prevalence of long-term opioid use by patients at the end of the study was just over 1%.

Yes, that’s right: 1%.

And the prevalence increased by just half a percentage point over a decade.

Hardly a crisis. Hardly anything to scream about.

But we can’t have that! We need a clickbait headline to demonize opioids and stop their prescribing! So, instead of reporting accurately on the very small increase in opioid prescribing, they focus on the “twofold” increase. Trying to manufacture a crisis where there is none.

It’s true, the prevalence of LTOT did double, from half a percent to one percent. And that’s what the headline highlighted, to try and make it sound like there is an opioid crisis in Europe. There is not.

This tactic is often used in presenting medical research – using relative percentages rather than the actual numbers. That is because relative percentages -- “Opioid Use Doubled!” -- sounds worse than “Opioid Use Increased by Half a Percent.”

It’s a trick that researchers and the media use all the time.

Why do this? It’s dishonest. It’s deceptive. And it destroys our trust in science. They are trying to manufacture a crisis when there is none.

Why not research and report an actual crisis? Instead of making one up?

The Physician’s Weekly headline exemplifies the worst of scientific spin: inflating tiny fractional changes and omitting context. It potentially harms patients by reinforcing the myth that opioids don’t work long term and should be withheld. That myth persists because of misleading reporting like this.

Finally! An Honest Headline

It was nice to see some accurate reporting in Scimex, an Australian online news portal that tries to help journalists cover science. Instead of the usual deceptive, sensationalist headlines, this one tells the truth:

“Pain Reprocessing Therapy (PRT) could help those with mild chronic back pain”

This was so refreshing to see! Because it’s so very, very rare.

Most reporting on PRT glosses over a critical point: It has only been studied in people with mild, non-specific back pain. An average of 4 on the zero-to-10 pain scale.

That nuance is often lost in the hype about alternative treatments like PRT, cognitive behavioral therapy, mindfulness and TENS.

You do not treat 8/10 back pain the same way you treat 4/10 back pain.

What happens when people are misled about PRT? It gets recommended to people with severe, pathological pain — often with clearly identifiable causes — and everyone acts surprised when it doesn’t work.

Let’s be clear:

• PRT is not for severe back pain

• PRT is not for pain caused by pathology

• PRT is not a cure-all

But you wouldn’t know that from most headlines about PRT, such as “New therapy aims to cure back pain without drugs, surgery” and “A New Way to Treat Back Pain.”

Then you read the small print: All the participants in PRT studies had non-specific back pain from an unknown cause. And they had mild pain.

The researchers are often complicit, cherry-picking and hyping their own data. Why? Because they need funding. Because they’re writing a book. Because professors have to "publish or perish" to keep their jobs. Because it’s easier to mislead the public than to admit a therapy has limits. And you don’t get to be a guru if your therapy only works for a minority of patients with mild pain.

This kind of spin harms people with severe chronic secondary pain. It feeds the narrative that if you're still in pain, then it’s your fault. You didn’t try hard enough. You’re catastrophizing. You need to retrain your brain.

It feeds the stigma that all chronic pain is mild and easily curable. And that anyone who says their pain is severe has psychological problems.

No. Maybe their pain is caused by pathology, like tissue damage or herniated discs. Maybe their pain is nociceptive or neuropathic.

This is why chronic pain patients must be included on every research team. Someone with real-world, high-impact chronic pain would never let this kind of misrepresentation slide. And the rest of the team wouldn’t be able to claim ignorance.

We need more honesty and integrity in research and the media. We need headlines that reflect the actual findings. We need conclusions that match the data, not some predetermined narrative. Right now, most media coverage doesn’t even try.

Read the study, then read the headline. They rarely match. That’s how we ended up with a generation of healthcare providers who think opioids are bad, all chronic pain is primary pain, and that PRT is some miracle therapy.

It’s not. PRT may be helpful to people who are depressed or have anxiety, but should not be a first-line treatment for everyone. It’s only been tested in people with mild back pain for which there is no known physical cause. It has not been shown to work for people with severe pain or structural pathology.

But the researchers usually gloss over that. And the headlines and conclusions rarely reflect those facts or spell out who PRT is for and who it is not for.

Because here’s the truth: Pain Reprocessing Therapy is not a treatment for chronic pain. It’s a treatment for anxiety and depression.

That’s the real headline.

Neen Monty is a patient advocate in Australia who lives with rheumatoid arthritis and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), a progressive neurological disease that attacks the nerves.

Neen is dedicated to challenging misinformation and promoting access to safe, effective pain relief. She has created a website for Pain Patient Advocacy Australia to show that prescription opioids can be safe and effective, even when taken long term. You can subscribe to Neen’s free newsletter on Substack, “Arthritic Chick on Chronic Pain.”

Endometriosis Linked with Hundreds of Comorbidities

By Pat Anson

Endometriosis is one of the most frustrating and debilitating conditions a woman can have, causing physical, sexual and emotional pain that’s difficult to diagnose and treat.

Patients who have endometriosis are often told it’s “all in your head” or that “you’ll grow out of it.” Few of them do. Nearly 200 million people worldwide suffer from endometriosis, including about one in 10 American women.

A new study at the University California-San Francisco (UCSF) is providing new insights into endometriosis, linking it with hundreds of comorbidities such as cancer, Crohn's disease, and migraine. The research could improve how endometriosis is diagnosed and treated – ending some of the silence and misconceptions about the disease.

Researchers analyzed the electronic health records of over 43,000 people with endometriosis, comparing them to a large control group without the disease. Their findings are published in the journal Cell Reports Medicine 

“We now have both the tools and the data to make a difference for the huge population that suffers from endometriosis,” says senior author Marina Sirota, PhD, a professor of pediatrics and interim director of the UCSF Bakar Computational Health Sciences Institute. “We hope this can spur a sea change in how we approach this disorder.”

Endometriosis or “endo” occurs when blood-rich tissue that grows in the uterus is expelled each month during menstruation, spreading to the ovaries, fallopian tubes, abdomen and other nearby organs. The misplaced endometrial cells implant themselves in the new host tissue and grow, causing internal bleeding, inflammation and pain.

The wayward cells can be removed by surgery, but endometriosis is usually treated with hormones to suppress the menstrual cycle. Not everyone responds to surgery or hormonal therapy, which can have side effects. Removal of the uterus is a last-ditch treatment usually reserved for older women, but some women continue to have pain even after a hysterectomy.

“Endo is extremely debilitating,” said co-author Linda Giudice, MD, a physician-scientist in UCSF’s obstetrics, gynecology and reproductive sciences department. “The impact on patients’ lives is huge, from their interpersonal relationships to being able to hold a job, have a family, and maintain psychological well-being.”

In analyzing patient data, researchers looked for comorbidities linking endometriosis with other medical conditions, and found over 600 of them. Some were previously known, such as infertility, autoimmune disease, and migraine. Some were unexpected: certain cancers, asthma, and eye-diseases. The findings support the growing understanding of endometriosis as a “multi-system” disorder that causes dysfunction throughout the body. 

“This is the kind of data we need to move the needle, which hasn’t moved in decades,” Giudice said. “We’re finally getting closer to faster diagnosis and, eventually, we hope, tailored treatment for the millions of women who suffer from endometriosis.”

The association of endometriosis with migraine, for example, opens the possibility of treating endometriosis pain with medications that block calcitonin gene–related peptides (CGRPs), a relatively new class of migraine drug. In recent years, the FDA has approved over half a dozen CGRP medications for migraine prevention and/or treatment.

CGRP medications tend to be expensive, but so is endometriosis. One study estimates that the lifetime cost of having endometriosis in the U.S. is about $27,855 per year per patient, or about $22 billion annually. 

Poor Nutrition Linked to Higher Risk of Chronic Pain

By Crystal Lindell

Vitamin and mineral deficiencies could play a key role in chronic pain, according to new research that found low levels of Vitamin D, B12, folate and magnesium were common in people with severe chronic pain. 

The study, led by researchers at the University of Arizona Health Sciences, analyzed health data on over 220,000 people in the National Institutes of Health’s “All of Us” Research Database. The study is the first to look at micronutrient levels of people with and without chronic pain on a large scale.

“I treat chronic pain patients, and oftentimes we don’t come up with a diagnosis. But just because there isn’t a surgery that will help you doesn’t mean you’re not in pain. It just means that our understanding of pain is limited to date,” said senior author Julie Pilitsis, MD, head of the Department of Neurosurgery at U of A College of Medicine–Tucson.

“This study is a novel way to approach chronic pain treatment, where you are looking at the patient holistically to see what could be going on systemically that is easily modifiable – changes in diet as opposed to medications or other things.”

Pilitsis and her colleagues focused on five micronutrients commonly associated with chronic pain: vitamins D, B12, and C, folate and magnesium. Nutritional data was analyzed for people without pain, those with mild-to-moderate chronic pain, and people with severe chronic pain.

They found that people with severe chronic pain were more likely to have deficiencies in vitamin D, vitamin B12, folate and magnesium. The findings, however, varied depending on gender, race and ethnicity.

“The finding that surprised us the most was that Asian females had higher vitamin B12 levels than expected,” said co-author Deborah Morris, PhD, a research laboratory manager in the Department of Neurosurgery. “Asian females with severe chronic pain had the highest vitamin B12 levels overall. We were expecting it to be lower.”

The results also varied for vitamin C, where males with mild-to-moderate or severe chronic pain were more likely to have low or borderline low levels of vitamin C, compared to males without pain. 

Researchers caution that they didn’t prove a cause-and-effect relationship between nutrition and pain, but they believe their findings could lead to personalized diets and nutritional supplements for people with chronic pain. 

The Western Diet, which is common in the United States, is deficient in fruits and vegetables and contains high amounts of meat, refined grains, and desserts. This could contribute to nutritional imbalances and deficiencies in micronutrients. 

Frustratingly, like so much medical research regarding chronic pain these days, it seems one of the primary goals of the researchers is to reduce opioid use. 

“Our goal is to improve the quality of life for people with chronic pain and reduce opioid usage, and these findings have the potential to do that as part of a holistic approach to pain management,” said Morris. 

Note how she doesn’t say she wants to help patients reduce ibuprofen or gabapentin use, despite the fact that both can cause serious side effects. 

I’m glad to see more progress when it comes to understanding the causes of chronic pain –  especially since I suffer from it – but constantly framing every advancement as a way to “reduce opioid use” is disappointing. Opioid prescriptions have already been greatly reduced to levels not seen in over 20 years.

While chronic pain patients should obviously be making sure their vitamin and mineral levels are within the normal range, my fear is that doctors will over-correct – and start pushing vitamins and supplements as alternatives to pain medication. 

I myself suffered from extremely low vitamin D levels, and I do find that keeping it in the normal range helps reduce my pain levels. Holistic treatments can be a good thing, but only if they are truly holistic – encompassing both non-traditional and traditional approaches. 

Learn the Latest Advances in Adhesive Arachnoiditis at a Free Seminar

By Pat Anson

If you suffer from adhesive arachnoiditis (AA) or would like to learn more about it, there’s a unique opportunity next month to learn about the latest research and treatments for AA, and to connect with other patients, advocates and physicians.

The Tennant Foundation and the Arachnoiditis & Chronic Meningitis Collaborative Research Network (ACMCRN) are hosting a one-day seminar on Saturday, August 16 in Westminster, Colorado outside Denver. Lodging, meals and transportation are not provided, but the conference itself is free of charge.

AA is a spinal disease that causes chronic inflammation in the arachnoid membrane that covers the spinal canal. When nerves in the spine also become inflamed, they can adhere or stick together, causing severe pain and a wide variety of other symptoms.  

AA can develop after surgery or trauma that damages the spine. It may also be triggered by an inflammatory autoimmune disease that originates outside the spine that spreads into spinal tissue.

There is no cure for AA, but advances are being made in its treatment. The problem is that few practitioners know how recognize the early symptoms of AA, much less how to diagnose and treat it. That’s why conference organizers hope physicians will attend, along with patients, caregivers and family members.   

“We'll take whoever is interested,” says Dr. Forest Tennant, who is recognized as the world’s leading expert in AA. “We'd like to have many nurse practitioners or physicians who really want to know the disease. We're going to cover it backwards and forwards. We hope to make them educators and advocates for the disease.”  

Tennant has developed a unique protocol to treat AA not only with pharmaceuticals, but with hormones, vitamins and supplements that can help ease the symptoms and slow or prevent the disease from spreading.

“I want to get across the point that treating arachnoiditis is no more difficult than treating emphysema or rheumatoid arthritis or high blood pressure. It can be done in a primary care setting quite easily. It is not something that has to be done at the Mayo Clinic or in a sophisticated medical setting. It can be done in any office,” says Tennant.

Also speaking at the conference is Eve Blackburn, VP of Patient Engagement for ACMCRN, who will talk about the resources her organization has for patients, including a list of physicians that treat AA.  

“I’ll be sharing an update on the relaunch of the International Arachnoiditis Patient Registry, which is currently undergoing final steps in the ethics review process. We anticipate reopening within the next two months through our new secure platform, Digital Cabinet. I’ll also highlight our growing peer support programs, our referral list of Arachnoiditis-aware physicians, and the wide range of educational resources available at acmcrn.org,” said Blackburn.

The conference is not just for people diagnosed with AA. Since the disease is often associated with autoimmune disease or other types of spinal problems, patients suffering from those conditions could also learn important lessons at the seminar.  

“I call them associated diseases. Ehlers-Danlos syndrome, Tarlov cyst, and the Epstein Barr virus, those three in particular, as well as other spinal conditions. You can't talk about arachnoiditis unless you're also talking about autoimmunity and these other conditions that are high risk factors for developing the disease,” says Tennant.

The August 16 seminar is being held at the Marriott Hotel in Westminster, Colorado — which a special rate for conference attendees. Click here for more details.

You can also visit the conference website for hotel information and list of phone numbers to call if you have any questions. All attendees are encouraged to register by August 1.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. Readers interested in learning more about his research should visit the Tennant Foundation’s website, Arachnoiditis Hope. You can subscribe to its research bulletins here.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Microsoft Says Its AI Medical Tool is 4x Better Than Doctors at Diagnosing Patients

By Crystal Lindell

Microsoft is making some bold claims about the medical diagnosis tool it’s developing using artificial intelligence (AI). The company claims it is four times more accurate than a group of experienced physicians and can “solve medicine’s most complex diagnostic challenges.”.

Specifically, Microsoft’s AI Diagnostic Orchestrator – MAI-DxO for short — was able to correctly diagnose 85% of complex medical cases published in the New England Journal of Medicine (NEJM).

By comparison, when the company asked 21 practicing physicians from the US and UK to look at the same medical cases and provide a diagnosis, the human doctors were only accurate 20% of the time. 

In a demonstration video, Microsoft showed that MAI-DxO was able to order medical tests and provide the estimated financial costs for each test. It was then able to evaluate the test results and arrive at the correct diagnosis, even if the diagnosis was for an incredibly rare disease. 

“Our MAI-DxO orchestrator can handle some of the world’s toughest diagnoses with higher accuracy and lower costs. It puts us on the path to medical superintelligence - a big step towards better, more accessible care for all,” Microsoft said.

The company said it began testing its medical AI diagnosis systems with the United States Medical Licensing Examination, which is the same exam that physicians must pass to practice medicine in the United States. The test is a standardized assessment of clinical knowledge and decision making. 

But the fact that it was a standardized test made it too easy for AI. Microsoft said its orchestrator was able to get near-perfect scores within just three years. 

"These tests primarily rely on multiple-choice questions, which favor memorization over deep understanding," the company said. "By reducing medicine to one-shot answers on multiple-choice questions, such benchmarks overstate the apparent competence of AI systems and obscure their limitations."

To make its evaluations more challenging, Microsoft turned to having its AI evaluate the real-life cases published in the NEJM. 

MAI-DxO was configured to operate within different sets of cost constraints – just like in the real world when a patient’s care may be determined by what kind of health insurance they have, if any. That’s an important feature because without financial constraints, the orchestrator might default to ordering every possible test – regardless of cost, delays in care, or patient discomfort.

They also found that MAI-DxO delivered both higher diagnostic accuracy and lower overall costs than physicians or any other model they tested.   

"AI [could] reduce unnecessary healthcare costs,” the company said. "This kind of reasoning has the potential to reshape healthcare.”

Microsoft also touched on something that many patients with complex health challenges already know: the medical system is often overly reliant on siloed medical specialists. That’s another area where the company sees AI potentially improving patient care. 

With general practitioners treating a wide array of conditions and specialists focused on a single area of expertise, the hope is that AI would essentially be able to pull medical knowledge from both. 

While MAI-DxO seems to excel at tackling the most complex diagnostic challenges, Microsoft says further testing is needed to assess its performance on more common, everyday health conditions.

They also acknowledged that the clinicians in their study worked without access to colleagues, textbooks, or even AI – all tools that they may have in their day-to-day clinical practice. This was done to enable a fair comparison to raw human performance, but it also means that its unclear just how well AI actually competes against real-world physicians.

MAI-DxO is not available for commercial use yet. Microsoft said they need to do more testing to evaluate its reliability, safety, and efficacy. That could take about a decade. 

“It’s pretty clear that we are on a path to these systems getting almost error-free in the next 5-10 years. It will be a massive weight off the shoulders of all health systems around the world,” Mustafa Suleyman, chief executive of Microsoft AI, told The Guardian.

Descending Pain: A New Way to Control Severe Chronic Pain

By Dr. Forest Tennant and Ingrid Hollis

The control of severe chronic pain in medical practice today is almost exclusively based on “ascending” or “neuropathic” pain:

Ascending pain occurs when a pain signal is transmitted from the site of injury or disease up the spinal cord to the brain. Neuropathic pain is the pain that results when there is damage or dysfunction of nerve tissue in the brain, spinal cord or peripheral nerves. 

In recent years, researchers discovered that when chronic pain centralizes, it creates a third type of pain called “descending” pain. This is a critical issue for persons with adhesive arachnoiditis and other diseases that cause severe chronic pain, because descending pain requires different medications than those used for ascending and neuropathic pain.

A person with constant pain will produce excess bioelectricity (central sensitization or centralized pain) in the glial cell matrix of the brain. This bioelectricity “descends” or travels down the spinal cord and vagus nerve. It not only produces pain, but over-stimulates the cardiovascular system. 

Descending pain is controlled by the noradrenergic receptor.  The neurotransmitter to this receptor is called noradrenalin or norepinephrine. 

Symptoms of Descending Pain

Descending pain will be present in persons who have constant, unremitting pain. Here are the symptoms:

• Pulse rate elevates

• Periodic hot flashes

• Cold hands/feet

• Excess sweating

• Allodynia (pain upon light touch) 

Over-Reliance on Opioids and Neuropathic Agents

The lack of awareness about descending pain is one reason why high doses of opioids and neuropathic agents (i.e., gabapentin, diazepam) may be over-prescribed. Physicians may simply raise the opioid or gabapentin dosage if they are not aware that the cause is descending pain.  What’s more, the increase in dosage may be ineffective or even harmful.

This also applies to opioids in implanted pumps.  Countless persons have been treated with an implanted device or “pain pump” with the erroneous belief that no medication, except intrathecal opioids, are needed.  Patients with these devices soon learn that their pain is poorly controlled by opioids alone. 

Opioids and neuropathic agents have little effect on descending pain.  It must be treated separately.

Pain treatment and relief are based on a medicinal that activates or stimulates a specific receptor (think “action point”) that is present in nerve cells in the brain, spinal cord or peripheral nervous system. Here is how the three types of pain and their receptors can be treated:

1. Ascending pain needs to be treated with medications that activate the endorphin or opioid receptor. 

2. Neuropathic pain control depends on activation of a receptor called gamma amino butyric acid (GABA). 

3. Descending pain control must activate the norepinephrine (noradrenalin) receptor.

To achieve good control of severe, chronic or intractable pain, all three of these receptors must be simultaneously activated.  Severe chronic pain is commonly undertreated, because all three receptors are not simultaneously activated.

Medication Classes for Descending Pain

Three medication classes are used to treat descending pain.  Medical practitioners and patients have choices, and can experiment to help decide which medications and supplements bring the most comfort.

1. Bioelectric Blockers: Tizanidine, propanolol, clonidine, tapentadol (Nucynta).

2. Receptor Activators: Modafanil (Provigil), methylphenidate (Ritalin), dextroamphetamine, amphetamine salts (Adderall), phentermine, lisdexamfetamine (Vynanse). Non-prescription activators: lion’s mane, mushroom extract, St. John’s wort, rhodiola, mucuna, whole adrenal gland.

3. Precursor (Amino Acids) of Noradrenaline: Phenylalanine at 1,000 to 2,000mg a day. Tyrosine at 1,000 to 2,000mg a day.

When not controlled, chronic pain, inflammation and autoimmunity will deplete a number of neurotransmitters and hormones.  When that happens, noradenaline (norepinephrine) will often be depleted. 

Supplements of either amino acids (phenylalanine or tyrosine) and daily protein intake may help reduce both background and flare pains. Phenylalanine and/or tyrosine need not be taken every day, but they are highly recommended at least two days a week. They can and should be taken with a bioelectric blocker or receptor activator.

Noradrenergic receptor activators do not raise pulse rate or blood pressure in a constant pain patient like they do in a normal person.  They may actually lower blood pressure and pulse rate.  That’s because chronic pain, inflammation and autoimmunity deplete noradrenalin.

One medication, tapentadol (Nucynta), is both an opioid and norandrenergic blocker. It is highly recommended.

Descending pain is a new discovery that must be recognized and controlled to achieve relief from severe chronic pain.  A sole reliance on opioid and neuropathic agents may often provide inadequate pain relief.

To learn more about descending, ascending and neuropathic pain, you can watch a recent episode of DocToks with Dr. Forest Tennant and Friends.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. Readers interested in learning more about his research should visit the Tennant Foundation’s website, Arachnoiditis Hope. You can subscribe to its bulletins here.

Ingrid Hollis is a person in pain, patient advocate, and advisor to the Tennant Foundation.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Why Ice Cream May Be Bad for Your Gut Health

By David Hilzenrath, KFF Health News

It’s a marvel of food technology: ice cream that resists melting. In a video explaining the science behind it, a seller of food chemicals shows scoops of ice cream holding their shape under hot lights. The super ingredient? Polysorbate 80.

Polysorbate 80 is an emulsifier, a chemical used to control the consistency of thousands of supermarket products. Other widely used emulsifiers or stabilizers include carboxymethyl cellulose, carrageenan, and maltodextrin.

Recently, such ingredients have been showing up in scientific studies for another reason: Researchers say they may cause a variety of health problems.

Studies have found that emulsifiers can alter the mix of bacteria in the gut, known as the microbiome or microbiota; damage the lining of the gastrointestinal tract; and trigger inflammation, potentially contributing to problems elsewhere in the body.

Emulsifiers and stabilizers are among the most common ingredients in ultra-processed foods, a prime target of the “Make America Healthy Again” campaign by Health and Human Services Secretary Robert F. Kennedy Jr.

They are on the department’s radar: Their potentially harmful effects were flagged in a document HHS recently produced to support Kennedy’s drive to eliminate petroleum-based food dyes. But they illustrate the complexity of the war on food additives.

They show how, when it comes to food science, regulators are chronically playing catch-up. In the meantime, for many ingredients, regulators and consumers alike are left in a gray zone between suspicion and proof of harm in humans.

Emulsifiers’ assault on the microbiome could help explain inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, metabolic disorders, and even cancer, the studies suggest.

“There is a lot of data showing that those compounds are really detrimental for the microbiota and that we should stop using them,” said Benoit Chassaing, a research director at the French National Institute of Health and Medical Research and a co-author of several related studies.

Yet much larger and more ambitious clinical trials in humans are needed, Chassaing added.

For Lewis Rands, who has suffered from gastrointestinal illness, the research fits his own experience as a consumer. Changing his diet to avoid emulsifiers has made a shocking difference, easing symptoms that were debilitating, Rands said.

“Clinically, many patients have reported an improvement in symptoms with such changes,” said Ashwin Ananthakrishnan, a gastroenterologist and researcher at Massachusetts General Hospital.

The scientific findings come with caveats. For instance, much of the research has been done in mice, or by mimicking the human gut in a tube. There are many unknowns. Not all emulsifiers have bad effects, or the same effects, and some people are thought to be much more vulnerable than others.

Even some researchers who have co-authored papers say that the substances have not been proven harmful to humans and that it’s too soon to say regulators should ban them.

Still, the research poses a challenge for the FDA. When emulsifiers began spreading through the food supply, the agency wasn’t focusing on the gut microbiome, a relatively recent scientific frontier, researchers said.

Martin Makary, appointed by President Donald Trump to head the FDA, mentioned the microbiome at his Senate confirmation hearing in March. Though he didn’t cite emulsifiers specifically or identify chemicals by name, he said substances that affect the microbiome deserve the FDA’s attention.

“There’s a body of research now that suggests concern with some of these ingredients,” Makary said. “We have to look at those ingredients, and you have my commitment to do so if confirmed as FDA commissioner.

“These chemicals are creating an inflammatory response in the gastrointestinal tract, and with an altered microbiome lining that GI tract, kids feel sick.”

The FDA and the Department of Health and Human Services did not respond to questions about Makary’s testimony.

However, when journalist Emily Kopp asked HHS for the science behind its recent announcement that it is phasing out petroleum-based food dyes, the agency provided a compilation of information on potentially harmful compounds commonly found in ultraprocessed foods. The document, which appeared to be a draft, included a section on emulsifiers, such as xanthan gum and carrageenan. It noted that the section needed more work.

HHS subsequently provided the document to KFF Health News.

As far back as 2020, an international organization for the study of inflammatory bowel diseases advised that, for people with those conditions, it “may be prudent to limit intake” of maltodextrin, carrageenan, carboxymethyl cellulose, and polysorbate 80.

Emulsifiers are developed from a variety of sources, including plants and bacteria. Some ingredients that might affect the microbiome show up in foods because they were deemed “generally recognized as safe,” or GRAS.

“New information may at any time require reconsideration of the GRAS status of a food ingredient,” the Code of Federal Regulations says.

Ben & Jerry’s vs Häagen-Dazs

Rands, a genetic scientist, took matters into his own hands to battle severe inflammatory bowel disease. The illness caused bloating, stomach pain, cramps, frequent bowel movements, and bleeding, he said.

It left him in a constant state of anxiety and stress, he added, wondering where the nearest bathroom was and whether he’d reach it in time. Even taking a walk around the block with his wife and baby near their home in Australia was problematic.

Then, on the advice of a dietitian, Rands began avoiding foods with emulsifiers: chemicals such as carboxymethyl cellulose, carrageenan, guar gum, xanthan gum, and maltodextrin — plus other additives.

For instance, instead of eating Ben & Jerry’s ice cream, he switched to Häagen-Dazs ice cream that is free of the substances at issue. The relief was dramatic.

“It’s a huge difference,” Rands said. “To me, it’s made more of a difference than any drug.”

He has been able to scale back or stop taking several drugs, which is an added relief — not least because some can have harmful side effects, and, he said, one was taking its toll.

Rands said he used a scientific approach, isolating variables in his diet and logging the results. Avoiding artificial sweeteners helps, he said, but most of the benefit relates to avoiding the emulsifiers.

Ben & Jerry’s did not respond to a request for comment.

‘Science That Hasn’t Been Done Yet’

The Consumer Brands Association, which represents makers of processed foods, stands behind use of the chemicals.

“Food safety and protecting the integrity of the food supply is priority number one for the makers of America’s food and beverage products,” Sarah Gallo, the group’s senior vice president of product policy, said in a statement. “Emulsifiers and thickening agents play an important role in improving food texture and consistency, and have been studied by the FDA through a rigorous scientific and risk-based process.”

Asked for specifics on how the FDA had analyzed potential effects on the microbiome, the group did not respond.

Chassaing said the chemicals were “never considered for the potential effect on the microbiota.”

Robert Califf, who led the FDA under Presidents Barack Obama and Joe Biden, said in an interview that scientists are just beginning to understand the microbiome. He compared it to where the field of genomics was 20 years ago, only much more complicated — “multiplied by a thousand dimensions.”

He said the substances “fell within the standards” when they were greenlighted. “But hopefully most people agree that the standards need to be upgraded,” he added.

“This is different than traditional food safety thinking about, ‘Does it cause an immediate problem?’” Califf said. “We’re talking about long-term health outcomes here.”

And has the FDA evaluated those?

“How could it? There was no way to do it,” Califf said. The answers will vary depending on the emulsifier, and “proving whether it’s bad or good is going to require rigorous science that hasn’t been done yet.”

More recent scientific capabilities expand the possibilities, he said.

‘A Lot of Confusion in the Field’

For a consumer, trying to steer clear of emulsifiers can be difficult. Without realizing it, people can consume a variety of emulsifiers from a variety of foods — and the same chemicals from multiple sources.

Polysorbate 80 was listed as an ingredient on the labels of 2,311 products as of May 12, according to an online database posted by the Environmental Working Group using information from NielsenIQ. Carrageenan was listed on 8,100 product labels; maltodextrin, 12,769; and xanthan gum, 17,153.

Some emulsifiers have multiple names, making them harder to recognize. Some names can apply to more than one emulsifier. And some chemical names that appear on product labels don’t appear in the FDA’s “Substances Added to Food” inventory.

Carboxymethyl cellulose — not to be confused with methyl cellulose — is also known as carboxymethylcellulose  and cellulose gum. Maltodextrin can be derived from substances such as cornstarch, rice starch, and wheat starch — but the FDA doesn’t consider it synonymous with the term “modified food starch.”

The naming practices can frustrate efforts to track the chemicals in food, to measure how much of the stuff people are taking in, and even to figure out precisely which chemicals a scientific study evaluated, researchers said.

“There’s a lot of confusion in the field,” said Christine McDonald, a researcher at the Cleveland Clinic who has studied maltodextrin. She called for more consistent naming of additives in the United States.

The very term “emulsifier” is problematic. By strict definition, emulsifiers create an emulsion — a stable blend of liquids that would not otherwise mix, such as oil and water. However, the term is used broadly, encompassing chemicals such as maltodextrin that thicken, stabilize, or alter texture.

Gummed Up

Emulsifiers can be found in foods marketed as natural or healthy as well as ones that look artificial. Some products contain multiple emulsifiers.

Products sold at Whole Foods, for instance, list a variety of emulsifiers on their labels. 365 brand Organic Vegan Ranch Dressing & Dip contained organic tapioca maltodextrin and xanthan gum.

Pacific Seafood Starfish brand Cornmeal Crusted Fishsticks — marked as wild-caught and MSC-certified (sustainably sourced) — contain guar gum. Flour tortillas by 365 included monoglycerides of fatty acids and “stabilizer (guar gum, xanthan gum, carrageenan).”

At a Safeway supermarket, Healthy Choice Grilled Chicken Pesto With Vegetables listed modified potato starch, modified corn starch, carrageenan, xanthan gum, and guar gum.

The label on Newman’s Own Caesar salad dressing said the product contained no artificial preservatives or flavors, no colors from an artificial source, and was gluten-free. The ingredient label listed, “as a thickener,” xanthan gum.

In response to questions for this article, Whole Foods Market said it prohibits more than 300 ingredients commonly found in food.

“Our experts evaluate ingredients for acceptability in all food products we sell based on the best available scientific research,” the company said in a statement provided by spokesperson Rachel Malish.

Safeway’s parent company, Albertsons Companies, did not respond to inquiries. Nor did Pacific Seafood, Newman’s Own, or Conagra Brands, which makes Healthy Choice.

A Growing Body of Research

Research on emulsifiers has been building in recent years.

For example, a study published in January by the Journal of Crohn’s and Colitis concluded that a diet low in emulsifiers is an effective treatment for mild or moderate Crohn’s disease. The eight-week clinical trial, which tracked 154 patients in the United Kingdom, focused on carrageenan, carboxymethyl cellulose, and polysorbate 80.

A study published in February 2024 in the journal PLOS Medicine found that higher intakes of carrageenan and mono- and diglycerides of fatty acids were associated with higher risks of cancer. The study observed 92,000 French adults for an average of 6.7 years.

A study published in September 2023 in The BMJ, formerly known as the British Medical Journal, found that intake of several types of emulsifiers was associated with the risk of cardiovascular disease. The study observed more than 95,000 French adults for a median of 7.4 years.

A series of earlier studies found that emulsifiers “can promote chronic intestinal inflammation in mice”; that two in particular, carboxymethyl cellulose and polysorbate 80, “profoundly impact intestinal microbiota in a manner that promotes gut inflammation and associated disease states”; and that, based on a laboratory study of human samples, “numerous, but not all, commonly used emulsifiers can directly alter gut microbiota in a manner expected to promote intestinal inflammation,” as recounted in a 2021 paper in the journal Microbiome.

Other findings diverge. A study from Australia, published in February in Alimentary Pharmacology and Therapeutics, followed 24 Crohn’s patients over four weeks and concluded that, in the context of a healthy diet, the emulsifier content had “no influence over disease activity.”

The authors declared conflicts of interest, including payments from PepsiCo, drug companies, and Mindset Health Pty, which promotes hypnosis-based therapy. One of the authors, gastroenterology professor Peter Gibson of Monash University in Australia, said the conflicts of interest “have nothing whatsoever to do with the study.”

“It is important not to overinterpret results of studies,” he said, adding that his team’s report “does not mean that emulsifiers are good for you or that there are no health benefits in avoiding emulsifiers.”

Häagen-Dazs ‘Keeps It Real’

Häagen-Dazs touts the absence of such chemicals as a virtue. “Keeping it real, the way it should be,” it said in an online plug for its vanilla ice cream. “No emulsifiers. No stabilizers.”

However, at the company that makes Häagen-Dazs in the United States, Dreyer’s Grand Ice Cream, there are limits to that approach.

Under other brand names — such as Edy’s, Dreyer’s, and Drumstick — it markets products that contain emulsifiers or stabilizers. The company did not respond to questions. In addition, a spokesperson for Nestlé, which markets Drumstick and Häagen-Dazs brands internationally, did not respond.

Drumstick Vanilla Caramel Sundae Cones have no artificial flavors or colors, the package says — but they feature an array of other ingredients, including soy lecithin, guar gum, monogylcerides, and carob bean gum.

The cones, the company’s website says, offer “one incredibly creamy experience.”

But the creamy filling doesn’t melt. Instead, over 24 hours on a KFF Health News reporter’s kitchen counter, it bled a caramel-tinged fluid and shrank into a sticky white foam that could be cut with a knife.

KFF Health News is a national newsroom that produces in-depth journalism about health issues.

Brain Receptor May Hold Key to Treating Neuropathic Pain

By Pooja Shree Chettiar and Siddhesh Sabnis  

Pain is easy to understand until it isn’t. A stubbed toe or sprained ankle hurts, but it makes sense because the cause is clear and the pain fades as you heal.

But what if the pain didn’t go away? What if even a breeze felt like fire, or your leg burned for no reason at all? When pain lingers without a clear cause, that’s neuropathic pain.

We are neuroscientists who study how pain circuits in the brain and spinal cord change over time. Our work focuses on the molecules that quietly reshape how pain is felt and remembered.

We didn’t fully grasp how different neuropathic pain was from injury-related pain until we began working in a lab studying it. Patients spoke of a phantom pain that haunted them daily – unseen, unexplained and life-altering.

These conversations shifted our focus from symptoms to mechanisms. What causes this ghost pain to persist, and how can we intervene at the molecular level to change it?

More Than Just Physical Pain

Neuropathic pain stems from damage to or dysfunction in the nervous system itself. The system that was meant to detect pain becomes the source of it, like a fire alarm going off without a fire. Even a soft touch or breeze can feel unbearable.

Neuropathic pain doesn’t just affect the body – it also alters the brain. Chronic pain of this nature often leads to depression, anxiety, social isolation and a deep sense of helplessness. It can make even the most routine tasks feel unbearable.

About 10% of the U.S. population – tens of millions of people – experience neuropathic pain, and cases are rising as the population ages. Complications from diabetes, cancer treatments or spinal cord injuries can lead to this condition. Despite its prevalence, doctors often overlook neuropathic pain because its underlying biology is poorly understood.

There’s also an economic cost to neuropathic pain. This condition contributes to billions of dollars in health care spending, missed workdays and lost productivity. In the search for relief, many turn to opioids, a path that, as seen from the opioid epidemic, can carry its own devastating consequences through addiction.

GluD1: A Quiet But Crucial Player

Finding treatments for neuropathic pain requires answering several questions. Why does the nervous system misfire in this way? What exactly causes it to rewire in ways that increase pain sensitivity or create phantom sensations? And most urgently: Is there a way to reset the system?

This is where our lab’s work and the story of a receptor called GluD1 comes in. Short for glutamate delta-1 receptor, this protein doesn’t usually make headlines. Scientists have long considered GluD1 a biochemical curiosity, part of the glutamate receptor family, but not known to function like its relatives that typically transmit electrical signals in the brain.

Instead, GluD1 plays a different role. It helps organize synapses, the junctions where neurons connect. Think of it as a construction foreman: It doesn’t send messages itself, but directs where connections form and how strong they become.

This organizing role is critical in shaping the way neural circuits develop and adapt, especially in regions involved in pain and emotion. Our lab’s research suggests that GluD1 acts as a molecular architect of pain circuits, particularly in conditions like neuropathic pain where those circuits misfire or rewire abnormally. In parts of the nervous system crucial for pain processing like the spinal cord and amygdala, GluD1 may shape how people experience pain physically and emotionally.

Fixing the Misfire

Across our work, we found that disruptions to GluD1 activity is linked to persistent pain. Restoring GluD1 activity can reduce pain. The question is, how exactly does GluD1 reshape the pain experience?

In our first study, we discovered that GluD1 doesn’t operate solo. It teams up with a protein called cerebellin-1 to form a structure that maintains constant communication between brain cells. This structure, called a trans-synaptic bridge, can be compared to a strong handshake between two neurons. It makes sure that pain signals are appropriately processed and filtered.

But in chronic pain, the bridge between these proteins becomes unstable and starts to fall apart. The result is chaotic. Like a group chat where everyone is talking at once and nobody can be heard clearly, neurons start to misfire and overreact. This synaptic noise turns up the brain’s pain sensitivity, both physically and emotionally. It suggests that GluD1 isn’t just managing pain signals, but also may be shaping how those signals feel.

What if we could restore that broken connection?

In our second study, we injected mice with cerebellin-1 and saw that it reactivated GluD1 activity, easing their chronic pain without producing any side effects. It helped the pain processing system work again without the sedative effects or disruptions to other nerve signals that are common with opioids. Rather than just numbing the body, reactivating GluD1 activity recalibrated how the brain processes pain.

Of course, this research is still in the early stages, far from clinical trials. But the implications are exciting: GluD1 may offer a way to repair the pain processing network itself, with fewer side effects and less risk of addiction than current treatments.

For millions living with chronic pain, this small, peculiar receptor may open the door to a new kind of relief: one that heals the system, not just masks its symptoms.

Pooja Shree Chettiar and Siddhesh Sabnis are neuroscience PhD candidates at Texas A&M University.

This article originally appeared in The Conversation and is republished with permission.

People Who Live in Rural Areas Have More Pain and Less Access to Treatment

By Crystal Lindell 

A new study by researchers at the University of Texas at Arlington found that people living in rural areas have significantly higher rates of chronic pain than those who live in big cities. They’re also at a big disadvantage when it comes to getting their pain treated.

As a rural resident myself for the last 11 years, I have some thoughts as to why this might be. I think one of the causes may be a little different than what researchers often assume. 

The study used data from a national health survey of over 10,000 people in 2019, and then followed up with them a year later in 2020. 

Respondents were split into four pain categories; those with no pain, nonchronic acute pain, chronic pain, and high-impact chronic pain (HICP), which is pain that significantly impacts daily life.

Participants were then assigned to one of four urban-rural metro areas based on where they live: Large Central Metro (big cities with at least one million people), Large Fringe Metro, Medium and Small Metro, and Non-Metropolitan (Rural).

The chart below shows that the highest rates of chronic pain (27.8%) and HICP (10.4%) were found in rural non-metropolitan areas. Pain rates were progressively lower in metro areas with more people. 

Notably, 43.1% of the people living in big cities had “no pain,” while only 34% of those in rural areas were pain free. That’s a statistically big difference.

The Journal of rural health

“We already know about the rural-urban gap in mortality and life expectancy,” said Feinuo Sun, PhD, an assistant professor of kinesiology at UT Arlington and lead author of the study in The Journal of Rural Health.

“But when you look at pain, especially chronic pain, it becomes clear that rural residents face additional burdens.”

Sun and her colleagues say their findings highlight the rural disadvantage that exists in pain development and treatment. Due to health care shortages in rural areas, people have limited access to pain treatment and lower quality services.

They also found that the percentages of people transitioning from milder pain conditions in 2019 to more severe ones in 2020 were highest in rural areas. Even when starting from the same baseline pain status, people in rural areas fared worse after one year compared to those in urban areas.

“Without early intervention, (chronic pain) can have serious long-term consequences, including premature mortality. That's why targeted outreach and early pain management strategies are so important," said Sun.

Rural residents are also more likely to work physically demanding jobs and experience higher poverty rates, both of which contribute to chronic pain.

Those are definitely contributing factors. People who live near me in northern Illinois tend have more physically demanding work, such as farming and construction, and they have a much harder time accessing good healthcare. 

Personally, I have to drive almost two hours each way just to see my primary care physician, because I have to get more complex pain care. That’s where the closest university hospital is to my house. 

Lower Cost of Living

But there’s another reason that is easy to overlook if you don’t live out here: Rural areas are much cheaper than urban ones. 

That’s literally the reason I choose to live in a rural area. The rent in my area is astronomically cheaper than nearby metro areas, and much less compared than a big city like Chicago. 

If you're managing a life with chronic pain, you’re going to be less likely to be able to work and you’re also going to be more likely to spend more of your income on medical expenses. You’ll need a cheaper place to live.

Additionally, many people move out to rural areas like mine because it’s easier to live on Social Security, disability or pensions. None of those benefits increase based on your local cost of living, so it makes sense to live in a rural area where the same amount of money can go much further. 

So it’s not always physically demanding labor that causes more pain in rural areas. It’s being in chronic pain that makes it more likely you’ll move to or stay in a rural community.

Of course, the researchers also found an association with opioid medication, because what would a pain study be in 2025 if the authors didn’t link it in some way to opioids?

The UT researchers think that  “elevated pain levels, along with fewer treatment options, may help explain the heavier reliance on opioids” in rural communities. They’re already working on a follow-up study to examine disparities in pain care. I can already tell them some of the answers they seek. 

People in rural areas are more likely to take opioids for pain care because they are incredibly cheap and accessible. Even if a rural area doesn’t have a local pharmacy, you still have access to mail-order pharmacies. 

And if a rural area doesn’t have a physical therapist, acupuncturist or a massage therapist, there are few alternatives besides opioids. Opioids also require fewer appointments with providers, which are at a premium when doctors are 2 hours away or more.

In the end, geography shapes both our pain and standard of living. Rural areas need better access to healthcare and more populated areas need lower costs of living. We can help people, we just have to work in both directions.