Premenstrual Disorder Causes Despair for Some Women

By Lauren Peace, KFF Health News

For the most part, Cori Lint was happy.

She worked days as a software engineer and nights as a part-time cellist, filling her free hours with inline skating and gardening and long talks with friends. But a few days a month, Lint’s mood would tank. Panic attacks came on suddenly. Suicidal thoughts did, too.

She had been diagnosed with anxiety and depression, but Lint, 34, who splits her time between St. Petersburg, Florida, and Tulsa, Oklahoma, struggled to understand her experience, a rift so extreme she felt like two different people.

“When I felt better, it was like I was looking back at the experience of someone else, and that was incredibly confusing,” Lint said.

Then, in 2022, clarity pierced through. Her symptoms, she realized, were cyclical. Lint recognized a pattern in something her doctors hadn’t considered: her period.

CORI LINT

For decades, a lack of investment in women’s health has created gaps in medicine. The problem is so prevalent that, this year, President Joe Biden signed an executive order to advance women’s health research and innovation.

Women are less likely than men to get early diagnoses for conditions from heart disease to cancer, studies have found, and they are more likely to have their medical concerns dismissed or misdiagnosed. Because disorders specifically affecting women have long been understudied, much remains unknown about causes and treatments.

That’s especially true when it comes to the effects of menstruation on mental health.

When Lint turned to the internet for answers, she learned about a debilitating condition at the intersection of mental and reproductive health.

Sounds like me, she thought.

What Is PMDD?

Premenstrual dysphoric disorder, or PMDD, is a negative reaction in the brain to natural hormonal changes in the week or two before a menstrual period. Symptoms are severe and can include irritability, anxiety, depression, and sudden mood swings. Others include fatigue, joint and muscle pain, and changes to appetite and sleep patterns, with symptoms improving once bleeding begins.

Unlike the mild discomfort of premenstrual syndrome, or PMS, the effects of premenstrual dysphoric disorder are life-altering. Those afflicted, according to one estimate, can endure almost four years of disability, cumulatively, over their lives.

Though researchers estimate that the dysphoric disorder affects around 5% of people who menstruate — about the same percentage of women with diabetes — the condition remains relatively unknown, even among health care providers.

In a 2022 survey of PMDD patients published in the Journal of Women’s Health, more than a third of participants said their family doctors had little knowledge of the premenstrual disorder or how to treat it. About 40% said the same was true of their mental health therapists.

Reproductive mental health has been sidelined as a specialty, said Jaclyn Ross, a clinical psychologist who researches premenstrual disorders as associate director of the CLEAR Lab at the University of Illinois-Chicago. Only some health care providers get training or even become aware of such disorders, Ross said.

“If you’re not considering the menstrual cycle, you’re at risk of misdiagnosing and missing what’s actually going on,” Ross said.

That was the case for Tampa, Florida, resident Jenna Tingum, 25, who had panic attacks and suicidal thoughts as a premed student at the University of Florida. It wasn’t until her college girlfriend read about PMDD online and noticed Tingum’s symptoms flared in the days leading up to her period that Tingum talked with her gynecologist.

“I don’t think I would have ever put the pieces together,” Tingum said.

Suicide Risk and Treatment

Because few researchers study the condition, the cause of PMDD is something of an enigma, and treatments remain limited.

It wasn’t until 2013 that the disorder was added to the Diagnostic and Statistical Manual, the handbook used by medical professionals in the U.S. to diagnose psychiatric conditions. PMDD was officially recognized by the World Health Organization in 2019, though references in medical literature date to the 1960s.

Defining the disorder as a medical condition faced early pushback from some feminist groups wary of giving credibility to stereotypes about PMS and periods. But Ross said patients must be taken seriously.

In one study, 72% of respondents with the disorder said they’d had suicidal thoughts in their lifetime. And 34% said they had attempted suicide, compared with 3% of the general population.

Marybeth Bohn lost her daughter, Christina Bohn, to suicide in 2021. It was only in the months before her death at age 33 that Christina connected her extreme distress to her cycle — no doctors had asked, Bohn said. Now Bohn, who lives in Columbia, Missouri, works with medical and nursing schools around the country to change curricula and encourage doctors to ask people in mental health emergencies about their premenstrual symptoms and cycles.

“We need more research to understand how and why these reactions to hormones occur,” Ross said. “There’s so much work to be done.”

While doctors haven’t settled on a universal approach to address the symptoms, three main treatments have emerged, said Rachel Carpenter, medical director of reproductive psychiatry at the University of Florida–Jacksonville College of Medicine.

Selective serotonin reuptake inhibitors, the most common form of antidepressants, are a first line of attack, Carpenter said. Some patients take the medication regularly; others in just the week or two that symptoms occur.

For some patients, hormonal birth control can alleviate symptoms by controlling or preventing the release of certain hormones.

Finally, talk therapy and cycle awareness can help patients build mental resilience for difficult weeks.

Sandi MacDonald, who co-founded the International Association for Premenstrual Disorders, a leading resource for patients and clinicians, said peer support is available through the nonprofit, but funding for research and education remains elusive.

She hopes the new White House initiative on advancing women’s health research will open doors.

‘I’m Not Crazy’

Both Lint and Tingum, who were diagnosed by medical professionals after learning about the disorder on their own, said a lack of conversation around periods contributed to their care being delayed.

Lint doesn’t remember talking much about periods in grade school; they were often the butt of a joke, used to dismiss women.

“For the longest time, I thought, ‘Well, this happens to everyone, right?’” Lint said of her symptoms. “Has a doctor ever asked me what my symptoms are like? No, absolutely not. But we’re talking about a quarter or more of my life.”

Brett Buchert, a former University of Florida athlete who took time away from campus because her symptoms were so severe, said that when doctors do ask questions, it can feel like boxes being checked: “The conversation ends there.”

Buchert, who graduated with a degree in psychology and now lives in Boulder, Colorado, said understanding what’s happening to her and being aware of her cycle has helped her manage her condition.

Lint and Tingum agreed.

Even as Lint struggles to find a medicine that brings relief, tracking her cycle has allowed her to plan around her symptoms, she said. She makes fewer commitments in the week before her period. She carves out more time for self-care.

She’s also found solace in reading stories of others living with the condition, she said.

“It’s helped me process the extremes,” Lint said. “There’s not something wrong with me as an individual. I’m not crazy; this is something that’s legitimately happening to me. It helps to know I’m not alone.”

This article was produced through a partnership between KFF Health News and the Tampa Bay Times. KFF Health News is a national newsroom that produces in-depth journalism about health issues.

Researchers Closer to Finding the Gene for Hypermobile EDS

By Crystal Lindell

We may be one step closer to discovering the specific gene mutations behind hypermobile Ehlers-Danlos syndrome (hEDS) — a connective tissue disorder that weakens collagen, muscles, ligaments and organs throughout the body, and makes joints highly flexible.

A research team at the Medical University of South Carolina has released the results of a genetic study of a family with high rates of hEDS. Five out of 11 family members met the clinical diagnostic criteria for hEDS and three were considered “probable.” 

Before we get too far into its conclusions though, it’s important to note that findings were released as a preprint in Research Square, which means they have not yet been peer-reviewed by a journal. As such, it’s in the early stages of release, and further scrutiny may result in changes to the conclusions.

That said, the researchers claim to have found what could be a variant linked to hEDS in the Kallikrein-15 gene, which is primarily expressed in the thyroid gland and other organs.

To check if this gene change actually causes hEDS, researchers used laboratory mice. After modifying the mice to have the same genetic variant, they found that the mice had similar connective tissue problems as seen in people with hEDS.

This supports the idea that the Kallikrein gene changes may play a role in causing hEDS.

But the research does not seem to show an all-encompassing hEDS gene. In a cohort of 197 hEDS patients, they found that less than a third (32.8%) had at least one KLK variant. Which means that over 60% of hEDS patients in the study did not have the variant.

As of now, hEDS is the only type of Ehlers-Danlos syndrome that does not have a known specific genetic marker, so finding one would be monumental. And even if this research doesn’t get us all the way there, it’s a huge step in the right direction.

Previous research has also associated hEDS to a genetic variant that causes a deficiency of folate, the natural form of Vitamin B9.

I should note here that I was diagnosed with hypermobile-EDS in 2018, so I have a lot of interest in the topic on a personal level. Since there is no genetic test currently available for hEDS, I was diagnosed via a physical assessment, along with my family’s medical history.

A lot of hEDS patients worry that if there ever is some sort of confirmed, definitive test like a genetic marker, they may not have the marker and would then “lose” their diagnosis.

Based on my personal experiences with medical professionals, I think that’s a legitimate fear. Doctors already seem unwilling to diagnose clear cases of hEDS for a variety of reasons, and this could just give them another excuse to continue doing that.

All I can really say is that if it happened to me, I would feel confident in knowing that my body is clearly not “normal” — so even if it’s not hEDS, there is something else impacting my health.

Some patients diagnosed with hEDS may actually be suffering from something else -- so a genetic test might help them to get the right diagnosis and treatment. I know that probably sounds naively optimistic to many patients. The more likely result is doctors telling patients nothing is wrong with them, and then sending them on their way to suffer.  

On the other hand, I think hEDS is so under-diagnosed, that having a definitive test for it would result in many, many more people finally getting an hEDS diagnosis.

Discovering the exact gene responsible for hEDS could also result in better treatments going forward. As of now, most doctors tell hEDS patients that there’s no cure, so all they can really do is treat the symptoms as they arise and avoid activities that could make their condition worse.  

This is purely wishful thinking, but perhaps in the future researchers will someday discover a way to actually strengthen our collagen and connective tissue, which could have countless benefits for patients suffering from the pain and other common hEDS symptoms.

Advancements like that still feel a long way off though, so until they happen, helping people get an hEDS diagnosis through a genetic test would be progress for millions of patients.

Can Complex Regional Pain Syndrome Be Cured?

By Pat Anson

A recent study by Australian researchers is challenging the notion that Complex Regional Pain Syndrome (CRPS) cannot be cured.

CRPS is a nerve disorder that often starts with an injury to an arm or leg, with the skin in the affected area becoming warm, red and painful to touch. Most cases are mild and people soon recover, but in rare cases it gets worse, resulting in chronic nerve pain that spreads throughout the body.  Because CRPS is difficult to predict, diagnose and treat, there’s been a long-held belief that it’s a lifelong illness.

“In this research we challenge the prevailing notion that CRPS is a lifelong burden,” says Michael Ferraro, a clinical researcher at the Centre for Pain IMPACT at Neuroscience Research Australia. “By reviewing and consolidating the latest developments in understanding CRPS, we’ve found that unlike previous theories, recovery is likely for most people with CRPS, and may be more likely with early diagnosis and a comprehensive treatment approach to match the multi-system nature of the disorder.”

Ferraro is lead author of a review in The Lancet Neurology, which maintains that 80% of CRPS patients can recover, if they are treated within the first 18 months of being diagnosed. The key is to “tackle CRPS from all angles” by combining pain medication, rehabilitation, and psychology with patient education about the condition.

Although the authors admit that “effective treatment of CRPS remains a challenge,” they think providers have learned a lot over the past five years about early identification of patients at high risk of CRPS, which is also known as Reflex Sympathetic Dystrophy (RSD).

“This is a major step towards better understanding CPRS. While more research is needed, our review highlights that biological and psychosocial factors are involved, and successful management of the disorder should target these factors,” says co-author Lorimer Moseley, PhD, a Professor of Clinical Neurosciences at University of South Australia. “The next steps will require national and international networks of researchers to test the most promising treatments in clinical trials.”

One study that’s already underway is the MEMOIR trial, funded by the Australian government, which is testing an analgesic drug and a newly developed rehabilitation program as potential treatments for CRPS.

Another recent study identified a genetic variant that may be involved in about a third of CRPS cases, which could potentially lead to earlier diagnoses.

Some CRPS patients are also finding relief through novel treatments, such as Scrambler therapy and ketamine infusions.

Volunteers Needed for Arachnoiditis Study

By Pat Anson

Kathleen Haynes knows all about the physical and emotional pain that comes from adhesive arachnoiditis (AA), a progressive spinal disorder that causes severe intractable pain.  

She’s had AA for 50 years, after an oily contrast dye used for a myelogram imaging test was injected into her spinal column. The invasive test turned a simple back injury into a living nightmare, with the nerves in her lower spine becoming inflamed and sticking together.

“That oil stayed in my spinal column, surrounded my spinal nerves, and that’s why my nerves clumped together,” Haynes said. “And it just got worse and worse and worse, to the point where I use a wheelchair to get around.”

At the young age of 70, Haines is now pursuing a doctorate degree in Psychology at Walden University. For her dissertation, she’s doing a study about suicide ideation in AA patients. In the past, Haynes had suicidal thoughts herself.

“The pain was just unbearable. And not being believed that I was in pain and not getting the right medication,” she told PNN.

“One of the things that was a deciding factor in doing this study was because I belong to a couple of AA groups on Facebook. And I was struck by the amount of people who go on there and say they're suicidal or say can you please lead me to somebody who does euthanasia?”  

KATHLEEN HAYNES

Haines’ goal is to interview 10 people with AA in the next few weeks who are not currently having suicidal thoughts, but are willing to talk about them. To protect their privacy, participants will be assigned numbers and their real names will not be used. A list of other conditions and sample questions can be found here, along with Haynes’ contact information.  

It’s not the just the pain that makes AA patients suicidal, according to Haynes. Other common factors are being disbelieved, ignored or marginalized by family, friends and doctors. Thoughts about “ending it all” occur so frequently that she thinks every AA patient should be evaluated for suicide ideation.   

“I want to see what people's common denominator is, in talking to them about their suicidality. The goal is to get this study together and get it out to the medical community because they barely recognize AA, yet alone the suicidality their patients face,” she said.

“They need to treat their patients with AA in a way that gives them a desire to live. And get them the treatment team, the providers that they need in order to live fairly comfortable life, despite their pain.” 

Like many other AA patients, Haynes had trouble being believed. She suffered her initial back injury while working for the U.S. Postal Service in the 1970’s, but only recently did the federal government approve her workers’ compensation claim, even though her AA diagnosis and disability happened a long time ago. The Massachusetts woman is now getting appropriate treatment and pain medication.        

To learn more about Haynes’ study and/or make a donation to her research, visit her GoFundMe page.

Medical Research Often Ignores Older Women

By Judith Graham, KFF Health News

Medical research has shortchanged women for decades. This is particularly true of older women, leaving physicians without critically important information about how to best manage their health.

Late last year, the Biden administration promised to address this problem with a new effort called the White House Initiative on Women’s Health Research. That inspires a compelling question: What priorities should be on the initiative’s list when it comes to older women?

Stephanie Faubion, director of the Mayo Clinic’s Center for Women’s Health, launched into a critique when I asked about the current state of research on older women’s health. “It’s completely inadequate,” she told me.

One example: Many drugs widely prescribed to older adults, including statins for high cholesterol, were studied mostly in men, with results extrapolated to women.

“It’s assumed that women’s biology doesn’t matter and that women who are premenopausal and those who are postmenopausal respond similarly,” Faubion said.

“This has got to stop: The FDA has to require that clinical trial data be reported by sex and age for us to tell if drugs work the same, better, or not as well in women,” Faubion insisted.

Consider the Alzheimer’s drug Leqembi, approved by the FDA last year after the manufacturer reported a 27% slower rate of cognitive decline in people who took the medication. A supplementary appendix to a Leqembi study published in the New England Journal of Medicine revealed that sex differences were substantial — a 12% slowdown for women, compared with a 43% slowdown for men — raising questions about the drug’s effectiveness for women.

This is especially important because nearly two-thirds of older adults with Alzheimer’s disease are women. Older women are also more likely than older men to have multiple medical conditions, disabilities, difficulties with daily activities, autoimmune illness, depression and anxiety, uncontrolled high blood pressure, and osteoarthritis, among other issues, according to scores of research studies.

Even so, women are resilient and outlive men by more than five years in the U.S. As people move into their 70s and 80s, women outnumber men by significant margins. If we’re concerned about the health of the older population, we need to be concerned about the health of older women.

As for research priorities, here’s some of what physicians and medical researchers suggested:

Heart Disease

Why is it that women with heart disease, which becomes far more common after menopause and kills more women than any other condition — are given less recommended care than men?

“We’re notably less aggressive in treating women,” said Martha Gulati, director of preventive cardiology and associate director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai, a health system in Los Angeles. “We delay evaluations for chest pain. We don’t give blood thinners at the same rate. We don’t do procedures like aortic valve replacements as often. We’re not adequately addressing hypertension.

“We need to figure out why these biases in care exist and how to remove them.”

Gulati also noted that older women are less likely than their male peers to have obstructive coronary artery disease — blockages in large blood vessels —and more likely to have damage to smaller blood vessels that remains undetected. When they get procedures such as cardiac catheterizations, women have more bleeding and complications.

What are the best treatments for older women given these issues? “We have very limited data. This needs to be a focus,” Gulati said.

Brain Health

How can women reduce their risk of cognitive decline and dementia as they age?

“This is an area where we really need to have clear messages for women and effective interventions that are feasible and accessible,” said JoAnn Manson, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston and a key researcher for the Women’s Health Initiative, the largest study of women’s health in the U.S.

Numerous factors affect women’s brain health, including stress — dealing with sexism, caregiving responsibilities, and financial strain — which can fuel inflammation. Women experience the loss of estrogen, a hormone important to brain health, with menopause. They also have a higher incidence of conditions with serious impacts on the brain, such as multiple sclerosis and stroke.

“Alzheimer’s disease doesn’t just start at the age of 75 or 80,” said Gillian Einstein, the Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging at the University of Toronto. “Let’s take a life course approach and try to understand how what happens earlier in women’s lives predisposes them to Alzheimer’s.”

Mental Health

What accounts for older women’s greater vulnerability to anxiety and depression?

Studies suggest a variety of factors, including hormonal changes and the cumulative impact of stress. In the journal Nature Aging, Paula Rochon, a professor of geriatrics at the University of Toronto, also faulted “gendered ageism,” an unfortunate combination of ageism and sexism, which renders older women “largely invisible,” in an interview in Nature Aging.

Helen Lavretsky, a professor of psychiatry at UCLA and past president of the American Association for Geriatric Psychiatry, suggests several topics that need further investigation:

• How does the menopausal transition impact mood and stress-related disorders?

• What nonpharmaceutical interventions (yoga, meditation, tai chi, etc.) can help older women recover from stress and trauma?

• What combination of interventions is likely to be most effective?

Cancer

How can cancer screening recommendations and cancer treatments for older women be improved?

Supriya Gupta Mohile, director of the Geriatric Oncology Research Group at the Wilmot Cancer Institute at the University of Rochester, wants better guidance about breast cancer screening for older women, broken down by health status. Currently, women 75 and older are lumped together even though some are remarkably healthy and others notably frail.

Recently, the U. S. Preventive Services Task Force noted “the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women 75 years or older,” leaving physicians without clear guidance.

“Right now, I think we’re underscreening fit older women and over screening frail older women,” Mohile said.

The doctor also wants more research about effective and safe treatments for lung cancer in older women, many of whom have multiple medical conditions and functional impairments. The age-sensitive condition kills more women than breast cancer.

“For this population, it’s decisions about who can tolerate treatment based on health status and whether there are sex differences in tolerability for older men and women that need investigation,” Mohile said.

Bone Health, Functional Health and Frailty

How can older women maintain mobility and preserve their ability to take care of themselves?

Osteoporosis, which causes bones to weaken and become brittle, is more common in older women than in older men, increasing the risk of dangerous fractures and falls. Once again, the loss of estrogen with menopause is implicated.

“This is hugely important to older women’s quality of life and longevity, but it’s an overlooked area that is understudied,” said Manson of Brigham and Women’s.

Jane Cauley, a distinguished professor at the University of Pittsburgh School of Public Health who studies bone health, would like to see more data about osteoporosis among older Black, Asian, and Hispanic women, who are undertreated for the condition. She would also like to see better drugs with fewer side effects.

Marcia Stefanick, a professor of medicine at Stanford University School of Medicine, wants to know which strategies are most likely to motivate older women to be physically active. And she’d like more studies investigating how older women can best preserve muscle mass, strength, and the ability to care for themselves.

“Frailty is one of the biggest problems for older women, and learning what can be done to prevent that is essential,” she said.

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

Research Suggests Chronic Pain Should be Treated Differently in Men and Women

By Pat Anson, PNN Editor

Why are women more likely than men to suffer from fibromyalgia, osteoarthritis, irritable bowel syndrome, and other chronic pain conditions?  

Various theories have been proposed over the years, such as gender bias in healthcare, the lingering effects of childhood trauma, and women “catastrophizing” about their pain more than men.

Now there’s a new theory, which could radically change how men and women are treated for pain.

In a groundbreaking study published in the journal BRAIN, researchers at University of Arizona Health Sciences identified two substances – prolactin and orexin B – that appear to make mice, monkeys and humans more sensitized to pain. Prolactin is a hormone that promotes breast development and lactation in females; while orexin B is a neurotransmitter that helps keep us awake and stimulates appetite.

Both males and females have prolactin and orexin, but females have much higher levels of prolaction and males have more orexin.  In addition to promoting lactation and wakefulness, both substances also appear to play a role in regulating nociceptors, specialized nerve cells near the spinal cord that produce pain when they are activated by a disease or injury.

“Until now, the assumption has been that the driving mechanisms that produce pain are the same in men and women,” says Frank Porreca, PhD, research director of the Comprehensive Center for Pain & Addiction at UA Health Sciences. “What we found is that the basic, underlying mechanisms that result in the perception of pain are different in male and female mice, in male and female nonhuman primates, and in male and female humans.”

Porreca and his colleagues made their discovery while researching the relationship between chronic pain and sleep.  Using tissue samples from male and female mice, rhesus monkeys and humans, they found that prolactin only sensitizes nociceptors in females, regardless of species, while orexin B only sensitizes the nociceptors of males.

The research team then tried blocking prolactin and orexin B signaling, and found that blocking prolactin reduced nociceptor activation only in female cells, while blocking orexin B only affected the nerve cells of males. In effect, they found that there are distinctive “male” and “female” nociceptors.  

“The nociceptor is actually different in men and women, different in male and female rodents, and different in male and female non human primates. That’s a remarkable concept, because what it's really telling us is that the things that promote nociceptive sensitization in a man or a woman could be totally different,” Porreca told PNN. “These are two mechanisms that we identified, but there are likely to be many, many more that have yet to be identified.”

Once such mechanism could be calcitonin gene-related peptides (CGRPs), a protein that binds to nerve receptors in the brain and trigger migraine pain. In a recent study, Porreca suggested that sexual differences may be the reason why migraine drugs that block CGRPs are effective in treating migraine pain in women, but are far less effective in men.  

Until these differences are more fully understood, Porreca says clinical trials should be designed to have an equal number of men and women. That way differences between the sexes could be more easily recognized and applied in clinical practice.

For example, therapies that block prolactin may be an effective way to treat fibromyalgia in women, while drugs that block orexin B might be a better way to treat certain pain conditions in men.

“We have an opportunity to develop therapies that could be more effective in treating pain in a man or in a woman than the generalized kinds of therapies that we use now,” said Porreca. ‘I think it's critically important that these pain syndromes really be taken very seriously. And that we find better ways of treating female pain and also male pain.” 

How Anesthesia Drugs Work in the Brain

By Dr. Adam Hines   

Over 350 million surgeries are performed globally each year. For most of us, it’s likely at some point in our lives we’ll have to undergo a procedure that needs general anaesthesia.

Even though it is one of the safest medical practices, we still don’t have a complete, thorough understanding of precisely how anaesthetic drugs work in the brain. In fact, it has largely remained a mystery since general anaesthesia was introduced into medicine over 180 years ago.

Our study published in The Journal of Neuroscience provides new clues on the intricacies of the process. General anaesthetic drugs seem to only affect specific parts of the brain responsible for keeping us alert and awake.

In a study using fruit flies, we found a potential way that allows anaesthetic drugs to interact with specific types of neurons (brain cells), and it’s all to do with proteins. Your brain has around 86 billion neurons and not all of them are the same – it’s these differences that allow general anaesthesia to be effective.

To be clear, we’re not completely in the dark on how anaesthetic drugs affect us. We know why general anaesthetics are able to make us lose consciousness so quickly, thanks to a landmark discovery made in 1994.

But to better understand the fine details, we first have to look to the minute differences between the cells in our brains. Broadly speaking, there are two main categories of neurons in the brain.

The first are what we call “excitatory” neurons, generally responsible for keeping us alert and awake. The second are “inhibitory” neurons – their job is to regulate and control the excitatory ones.

In our day-to-day lives, excitatory and inhibitory neurons are constantly working and balancing one another.

When we fall asleep, there are inhibitory neurons in the brain that “silence” the excitatory ones keeping us awake. This happens gradually over time, which is why you may feel progressively more tired through the day.

General anaesthetics speed up this process by directly silencing these excitatory neurons without any action from the inhibitory ones. This is why your anaesthetist will tell you that they’ll “put you to sleep” for the procedure: it’s essentially the same process.

A Different Kind of Sleep

While we know why anaesthetics put us to sleep, the question then becomes: “Why do we stay asleep during surgery?” If you went to bed tonight, fell asleep and somebody tried to do surgery on you, you’d wake up with quite a shock.

To date, there is no strong consensus in the field as to why general anaesthesia causes people to remain unconscious during surgery.

Over the last couple of decades, researchers have proposed several potential explanations, but they all seem to point to one root cause. Neurons stop talking to each other when exposed to general anaesthetics.

While the idea of “cells talking to each other” may sound a little strange, it’s a fundamental concept in neuroscience. Without this communication, our brains wouldn’t be able to function at all. And it allows the brain to know what’s happening throughout the body.

Our new study shows that general anaesthetics appear to stop excitatory neurons from communicating, but not inhibitory ones. This concept isn’t new, but we found some compelling evidence as to why only excitatory neurons are affected.

For neurons to communicate, proteins have to get involved. One of the jobs these proteins have is to get neurons to release molecules called neurotransmitters. These chemical messengers are what gets signals across from one neuron to another: dopamine, adrenaline and serotonin are all neurotransmitters, for example.

We found that general anaesthetics impair the ability of these proteins to release neurotransmitters, but only in excitatory neurons. To test this, we used Drosophila melanogaster fruit flies and super resolution microscopy to directly see what effects a general anaesthetic was having on these proteins at a molecular scale.

Part of what makes excitatory and inhibitory neurons different from each other is that they express different types of the same protein. This is kind of like having two cars of the same make and model, but one is green and has a sports package, while the other is just standard and red. They both do the same thing, but one’s just a little bit different.

Neurotransmitter release is a complex process involving lots of different proteins. If one piece of the puzzle isn’t exactly right, then general anaesthetics won’t be able to do their job.

As a next research step, we will need to figure out which piece of the puzzle is different, to understand why general anaesthetics only stop excitatory communication.

Ultimately, our results hint that the drugs used in general anaesthetics cause massive global inhibition in the brain. By silencing excitability in two ways, these drugs put us to sleep and keep it that way.

Adam Hines, PhD, is a Research Fellow at Queensland Brain Institute at The University of Queensland in Australia. His research focuses on combining neuroscience and artificial intelligence to develop “bio-inspired robotics.”

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

Support for Spouse with Chronic Pain Is Helpful, But Not Always Welcome

By Pat Anson, PNN Editor

Support for a spouse or romantic partner with chronic pain can help reduce depression and improve their mood, according to new study. But researchers say some people in pain have poor psychological health regardless of the support they receive.     

A Penn State research team conducted a series of interviews with 152 long-term couples over the age of 50 in which one of the partners had knee pain from osteoarthritis.

Nearly 40% of middle-aged Americans have knee osteoarthritis, a progressive and painful joint disorder that causes thinning of cartilage and joint damage. The condition is strongly associated with early death, high blood pressure, diabetes and cardiovascular disease, particularly in women.

“Osteoarthritis in the knee can be a challenging condition,” lead author Suyoung Nah, PhD, said in a press release “People with the condition will eventually need support managing their pain. What is more, they are likely to continue needing assistance managing their pain for the rest of their lives.”

Nah and her colleagues asked each couple about the pain management support they received from a spouse or partner, such as assistance in taking pain medication or help standing up.

Most participants who received good support felt loved and grateful, and had fewer signs of depression; while those who felt a lack of support had more negative moods and were more likely to be depressed.

A small group of respondents reported feeling angry or resentful — even when they received good support from a partner.

“Almost everyone has times in their life when they do not want to accept help because it makes them feel helpless or because they think they do not need it,” said co-author Lynn Martire, PhD, a Professor of Human Development and Family Studies at Penn State’s Center for Healthy Aging.

Researchers wanted to see if people’s perceptions of the support they receive changed over time, so 18 months later they surveyed the same couples again. Those who felt anger or resentment at the start of the study – regardless of the support they received -- continued having negative moods.

That finding demonstrates the need for good communication between couples when one partner has chronic pain. Providing support – and accepting it -- can be complicated in those relationships.

“Receiving care is not always beneficial to every aspect of a person’s life,” said Nah, who is currently a Postdoctoral Fellow at the Virginia Tech Center for Gerontology. “Additionally, it may be difficult for couples to discuss and negotiate care. As a society, we need to make sure that older people understand their partner’s needs and desires regarding care so that both partners can maximize their physical, emotional and relational quality of life.”

Previous research by Martire found that couples typically don’t have conversations about the type of support that is wanted or needed. Clear communication about expectations and feelings can improve the quality of life for a partner who needs care.

“My main interest is in late-life family relationships — especially couples — navigating chronic illness,” Martire said. “Most older adults have at least two or three chronic illnesses, so helping them find better ways to help each other is really important.”

The study was published in Journal of Aging and Health.

A 2017 study found that criticism from a spouse can make chronic back pain worse. People with back pain who felt they were criticized had more anxiety, anger and sadness, and their pain levels increased for as long as three hours. The study also found that when a partner was supportive – expressing concern about a spouse’s pain or giving “helpful” suggestions – the interaction was still perceived as negative by some pain sufferers.

Seniors Often Left Stranded in Emergency Rooms

By Judith Graham, KFF Health News

Every day, the scene plays out in hospitals across America: Older men and women lie on gurneys in emergency room corridors moaning or suffering silently as harried medical staff attend to crises.

Even when physicians determine these patients need to be admitted to the hospital, they often wait for hours — sometimes more than a day — in the ER in pain and discomfort, not getting enough food or water, not moving around, not being helped to the bathroom, and not getting the kind of care doctors deem necessary.

“You walk through ER hallways, and they’re lined from end to end with patients on stretchers in various states of distress calling out for help, including a number of older patients,” said Hashem Zikry, an emergency medicine physician at UCLA Health.

Physicians who staff emergency rooms say this problem, known as ER boarding, is as bad as it’s ever been — even worse than during the first years of the covid-19 pandemic, when hospitals filled with desperately ill patients.

While boarding can happen to all ER patients, adults 65 and older, who account for nearly 20% of ER visits, are especially vulnerable during long waits for care. Also, seniors may encounter boarding more often than other patients.

The best estimates I could find, published in 2019, before the covid-19 pandemic, suggest that 10% of patients were boarded in ERs before receiving hospital care. About 30% to 50% of these patients were older adults.

“It’s a public health crisis,” said Aisha Terry, an associate professor of emergency medicine at George Washington University School of Medicine and Health Sciences and the president of the board of the American College of Emergency Physicians, which sponsored a summit on boarding in September.

What’s going on? I spoke to almost a dozen doctors and researchers who described the chaotic situation in ERs. They told me staff shortages in hospitals, which affect the number of beds available, are contributing to the crisis. Also, they explained, hospital administrators are setting aside more beds for patients undergoing lucrative surgeries and other procedures, contributing to bottlenecks in ERs and leaving more patients in limbo.

Then, there’s high demand for hospital services, fueled in part by the aging of the U.S. population, and backlogs in discharging patients because of growing problems securing home health care and nursing home care, according to Arjun Venkatesh, chair of emergency medicine at the Yale School of Medicine.

Long Waits Risky for Seniors

The impact of long ER waits on seniors who are frail, with multiple medical issues, is especially serious. Confined to stretchers, gurneys, or even hard chairs, often without dependable aid from nurses, they’re at risk of losing strength, forgoing essential medications, and experiencing complications such as delirium, according to Saket Saxena, a co-director of the geriatric emergency department at the Cleveland Clinic.

When these patients finally secure a hospital bed, their stays are longer and medical complications more common. And new research finds that the risk of dying in the hospital is significantly higher for older adults when they stay in ERs overnight, as is the risk of adverse events such as falls, infections, bleeding, heart attacks, strokes, and bedsores.

Ellen Danto-Nocton, a geriatrician in Milwaukee, was deeply concerned when an 88-year-old relative with “strokelike symptoms” spent two days in the ER a few years ago. Delirious, immobile, and unable to sleep as alarms outside his bed rang nonstop, the older man spiraled downward before he was moved to a hospital room. “He really needed to be in a less chaotic environment,” Danto-Nocton said.

Several weeks ago, Zikry of UCLA Health helped care for a 70-year-old woman who’d fallen and broken her hip while attending a basketball game.

“She was in a corner of our ER for about 16 hours in an immense amount of pain that was very difficult to treat adequately,” he said. ERs are designed to handle crises and stabilize patients, not to “take care of patients who we’ve already decided need to be admitted to the hospital,” he said.

How common is ER boarding and where is it most acute? No one knows, because hospitals aren’t required to report data about boarding publicly. The Centers for Medicare & Medicaid Services retired a measure of boarding in 2021. New national measures of emergency care capacity have been proposed but not yet approved.

“It’s not just the extent of ED boarding that we need to understand. It’s the extent of acute hospital capacity in our communities,” said Venkatesh of Yale, who helped draft the new measures.

In the meantime, some hospital systems are publicizing their plight by highlighting capacity constraints and the need for more hospital beds. Among them is Massachusetts General Hospital in Boston, which announced in January that ER boarding had risen 32% from October 2022 to September 2023. At the end of that period, patients admitted to the hospital spent a median of 14 hours in the ER and 26% spent more than 24 hours.

Maura Kennedy, Mass General’s chief of geriatric emergency medicine, described an 80-something woman with a respiratory infection who languished in the ER for more than 24 hours after physicians decided she needed inpatient hospital care.

“She wasn’t mobilized, she had nothing to cognitively engage her, she hadn’t eaten, and she became increasingly agitated, trying to get off the stretcher and arguing with staff,” Kennedy told me. “After a prolonged hospital stay, she left the hospital more disabled than she was when she came in.”

What Seniors Can Do

When I asked ER doctors what older adults could do about these problems, they said boarding is a health system issue that needs health system and policy changes. Still, they had several suggestions.

“Have another person there with you to advocate on your behalf,” said Jesse Pines, chief of clinical innovation at US Acute Care Solutions, the nation’s largest physician-owned emergency medicine practice. And have that person speak up if they feel you’re getting worse or if staffers are missing problems.

Alexander Janke, a clinical instructor of emergency medicine at the University of Michigan, advises people, “Be prepared to wait when you come to an ER” and “bring a medication list and your medications, if you can.”

To stay oriented and reduce the possibility of delirium, “make sure you have your hearing aids and eyeglasses with you,” said Michael Malone, medical director of senior services for Advocate Aurora Health, a 20-hospital system in Wisconsin and northern Illinois. “Whenever possible, try to get up and move around.”

Friends or family caregivers who accompany older adults to the ER should ask to be at their bedside, when possible, and “try to make sure they eat, drink, get to the bathroom, and take routine medications for underlying medical conditions,” Malone said.

Older adults or caregivers who are helping them should try to bring “things that would engage you cognitively: magazines, books … music, anything that you might focus on in a hallway where there isn’t a TV to entertain you,” Kennedy said.

“Experienced patients often show up with eye masks and ear plugs” to help them rest in ERs with nonstop stimulation, said Zikry of UCLA. “Also, bring something to eat and drink in case you can’t get to the cafeteria or it’s a while before staffers bring these to you.”

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

Risk of Chronic Pain Doubles for People From Lower Socioeconomic Backgrounds

By Pat Anson, PNN Editor

People from lower socioeconomic backgrounds are twice as likely to develop chronic pain after an acute injury, according to UK researchers who found that smoking, fear of movement, and poor social support also raise the risk of chronic musculoskeletal pain (CMP).

The study, published in PLOS One, adds to a growing body of evidence linking economic, social and emotional stress to some chronic pain conditions.   

Researchers at the University of Birmingham analyzed over a dozen systematic reviews of clinical studies involving nearly half a million people with CMP. Their goal was to see what biopsychosocial factors are associated with CMP and potentially make pain treatment more difficult.

“The mechanisms of CMP are different to acute pain in that pain exists despite there no longer being evidence of ongoing healing, but rather due to a sensitized nervous system that creates a continued or repeated experience of pain despite no evidence of actual or potential tissue damage,” wrote lead author Michael Dunn, from the School of Sport, Exercise and Rehabilitation Sciences at University of Birmingham

“This transition from acute to chronic MSK pain is associated with the presence of many biopsychosocial factors such as fear avoidance, low mood, and work satisfaction or strain. Despite this, healthcare services conventionally utilize approaches to treat CMP based on understandings of acute MSK pain, with focus often on identifying and treating perceived injured or irritated MSK structures.”

Dunn and his colleagues say many treatments for MSK pain, such as physical therapy and surgery, work no better than a placebo. That is because they only focus on the injured body part, and fail to account for psychological and social factors that contribute to acute pain becoming chronic.

“Put simply, current healthcare approaches do not address all the reasons people do not get better,” Dunn said in a news release. “Not only are current healthcare approaches inadequate, they may also be discriminatory, with current healthcare approaches that are orientated around the injured body part being geared towards those from higher socioeconomic backgrounds who are less likely to experience these psychological or social factors.”

In addition to socioeconomic factors, Dunn says stress and depression also raise the risk of developing CMP. He doubts that any single risk factor is the sole cause of chronic pain, but a combination of them make recovery from an acute injury more problematic.

Dunn’s findings mirror those of several U.S. studies that found social and economic factors were intertwined with the prevalence of chronic pain. In a 2021 study, for example, nearly 45% of people living below the federal poverty level reported having back pain. Another study found that people who did not complete high school were significantly more likely to have joint pain from arthritis.   

People with less education often have blue-collar jobs requiring manual labor that may contribute to musculoskeletal pain. They also tend to have lower incomes and less access to healthcare.

Princeton researchers Angus Deaton and Anne Case were the first to report on the role socioeconomic issues play in so-called “deaths of despair,” which linked financial and social stress to rising rates of pain, suicide, substance abuse, and death in middle-aged white Americans.

How Gut Bacteria Changes the Immune System

By Dr. Narveen Jandu  

The human immune system changes with age. Immune responses start to become less robust as people get older, which makes them more vulnerable to certain infections and diseases.

However, immune system aging looks different from person to person. Research has shown that changes to the composition and diversity of the microorganisms in the gut may explain these differences in immune system aging.

The gut microbiome — the population of microorganisms that lives in the gastrointestinal tract — helps the body maintain a stable internal environment when it is faced with external changes. This is known as homeostasis. The gut microbiome supports homeostasis in different ways, such as through helping to keep the immune system alert, and digesting dietary fibre into short-chain fatty acids to strengthen the intestinal wall.

The gut microbiome also helps us to regulate our inflammatory reactions. Inflammation helps the body fight microorganisms that cause disease, and helps repair damaged tissues. However, as the composition of our gut microbiome changes with age, a low level of inflammation can become constant throughout the body. This is called inflammaging.

When inflammaging develops in the gut, it leads to a decrease in immune responses, which puts people at a higher risk for infection and disease.

Let’s take a closer look at the gut microbiome and how it changes with age.

Diversity of Bacteria Decreases with Age

Our gastrointestinal tract can be compared to a densely populated city inhabited by a variety of different bacteria, fungi, archaea and viruses collectively called the gut microbiota. In fact, compared to other parts of the body, the gut microbiome has the largest number of bacteria. In a healthy gut microbiome, there are four dominant families (or phyla) of microorganisms, including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria.

Firmicutes and Bacteroidetes make up around 80 to 90 per cent of the gut microbiota in the digestive tract. Firmicutes help with the production of short-chain fatty acids to support intestinal health and the secretion of mucus to improve intestinal wall defence. Bacteroidetes metabolize complex carbohydrates into vitamins and nutrients, and help promote glycogen storage to improve glucose metabolism.

The gut microbiome and immune system work closely together. The microorganisms in the gut send out signals that are detected by immune sensors. This allows the immune system to regulate the beneficial bacteria in the gut, helping maintain immune homeostasis. Through this interaction, the adaptive immune system also receives stimuli from harmful substances called antigens, which trigger an immune reaction.

However, as people age, the composition and balance of microorganisms in the gut changes. This gives rise to microbial dysbiosis, which means there is a reduction in the number of beneficial bacteria in the gut, alongside a higher number and pro-inflammatory organisms and bacteria that can cause disease. In addition to this, research has also shown that the general diversity of bacteria in our gut also decreases with age.

Over time, the shortage of beneficial bacteria such as Firmicutes in older adults starts to compromise the integrity of their intestinal barrier, causing it to become leaky. This is because the Firmicutes family plays a very important role in keeping the intestinal wall healthy and strong by producing a short-chain fatty acid called butyrate. Short-chain fatty acids such as butyrate help provide nutrients to strengthen the intestinal wall, inform immune responses and lower inflammation.

When intact, the intestinal barrier works to prevent harmful bacteria from passing through the intestinal wall, entering the circulatory system and reaching important organs. However, when there are not enough gut bacteria to produce the short-chain fatty acids that are needed for the intestinal wall to function, bacteria are able to enter the bloodstream. This contributes to the formation of intestinal inflammaging, which refers to a low level of inflammation that becomes steady throughout the body with age.

Inflammaging creates an environment that is prone to inflammation, which is caused and maintained by several factors. These can include microorganism imbalances in the intestines (microbial dysbiosis), psychological stress, physical inactivity, poor nutrition and chronic infections.

When the body is exposed to these factors on a regular basis, cellular senescence occurs. Cellular senescence is a state in which cell growth is permanently arrested, which means that cells are no longer able to self-renew. Eventually, this leads to a decrease in immune responses, which are important to prevent foreign substances and pathogens from entering the body.

How to Maintain a Healthy Balance of Bacteria

There is a common saying that claims “you are what you eat.” Indeed, nutrition and diet play an important role in regulating the number of different microorganisms that live in the gut. This means that diet may also play a key role in the immune function of older adults.

The Mediterranean diet, known for its lower intake of refined carbohydrates, saturated fats, dairy products and red meat, has been shown to have a positive effect on the balance of microorganisms in the gut and the strength of the intestinal barrier. The Mediterranean diet has also been linked to a lower risk of Type 2 diabetes in older adults, allowing these individuals to live a longer and healthier life.

The use of probiotics and prebiotics can also help fight age-related inflammation. Probiotics, such as Lactobacilli and Bifidobacteria, are live microorganisms that can be consumed to support overall health. More specifically, probiotics help improve the function of the intestinal barrier and regulate immune responses by modifying the composition of the gut microbiome. However, there is still some debate around whether the acidic conditions in the stomach allow probiotics to survive long enough to be able to move into the intestine.

It is clear that the immune system has an intricate relationship with the gut microbiome. A healthy and well-balanced gut microbiome will strengthen the intestinal barrier, which helps to reduce inflammation throughout the body and support the immune system.

To achieve this, it is important to maintain a healthy and well-balanced lifestyle as we grow older. This can include lower intake of dairy products and red meats, and harnessing the benefits of probiotics and prebiotics.

Narveen Jandu, PhD, is a faculty member with the School of Public Health Sciences at the University of Waterloo in Canada. As a biomedical researcher, Dr. Jandu’s research has focused on studying the cellular mechanisms and pathophysiological consequences of infectious diseases.

This article was co-authored by Flore Van Leemput. a student in health sciences at the University of Waterloo.

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

Epstein-Barr Virus Emerging As Possible Cause of Chronic Pain

By Dr. Forest Tennant, PNN Columnist 

When most people hear about the Epstein-Barr virus (EBV), they may recall its reputation as the rather harmless "kissing disease" known as mononucleosis.  To the surprise of many, this previously unheralded virus has recently emerged as a cause of some cancers and painful disorders.

It is now clear that EBV must be contained and suppressed in order to relieve the pain and suffering of many persons with chronic pain. This column is an introduction to the critical involvement of EBV with several chronic pain conditions.

The Epstein-Barr virus is named after Drs. Anthony Epstein and Yvonne Barr. In 1964, they discovered the virus after they found it in a cancer common in Africa called Burkitt’s Lymphoma.  Since that time, EBV has been found to cause other cancers including nasopharyngeal, gastric, Hodgkin’s lymphoma, and leukemia.  Some estimate that EBV causes about 200,000 cancers a year.

About three years after Epstein and Barr discovered EBV, it was found to be the cause of infectuous mononucleosis, which is known to trigger autoimmune complications.  Autoimmunity is simply defined as some element in the body that attacks, erodes, and destroys tissue. 

In 1968, this author reported that mononucleosis could cause glomerulonephritis, an autoimmune renal disease.  Over the ensuing decades, EBV has also been associated with other autoimmune disorders, including hepatitis, rheumatoid arthritis, fibromyalgia, systemic lupus, and Sjogren's syndrome.

EPSTEIN-BARR VIRUS

In 2018, a seminal study documented that EBV could cause a number of painful medical conditions by activating specific genes.  Dr. John Harley and colleagues at Cincinnati Children's Hospital Medical Center, with funding from the National Institutes of Health, found that a viral protein called Epstein-Barr nuclear analog 2 (EBNA 2) binds to the deoxyribonucleic acid (DNA) of genes that promote autoimmunity and some chronic pain conditions.

The pain conditions that Harley and his colleagues associated with EBV are multiple sclerosis, rheumatoid arthritis, celiac disease, type 1 diabetes, inflammatory bowel disease, thyroiditis, and juvenile arthritis.  Subsequent studies added Sjogren's syndrome, mixed connective tissue disease, and polymyositis to the list of EBV autoimmune conditions.

The Harley research is compelling.  We urgently need clinical studies of EBV in severe chronic pain patients to help develop new diagnostic, prevention, and treatment measures.  To this end, I've chosen to study the EBV relationship to painful spine and connective tissue diseases, especially adhesive arachnoiditis (AA) and Ehlers-Danlos syndrome (EDS). These conditions are considered intractable pain conditions in clinical pain practice. 

So far, we have collected EBV laboratory test results from over 80 persons with confirmed AA. Every case has demonstrated abnormally high levels of EBV IgG antibodies, which suggests the presence of autoimmunity and the possible invasion of brain and spinal tissue by the virus. 

Every patient with high IgG antibody levels also has herniated discs, and the majority have hypermobile EDS. Prior to developing AA, all had conditions associated with autoimmunity, such as fibromyalgia and small fiber neuropathy. All of them now have intractable pain.

How It Begins

Patients and clinicians concerned about chronic pain need to understand the basics of how EBV causes and aggravates chronic pain conditions. 

EBV is a member of the herpes virus family, which includes the other herpes viruses and cytomegalovirus.  It is a natural, lifelong parasite that usually infects children before the age of two. 

When EBV first enters the body, it is an “active” virus that may cause a cold, sinusitis, bronchitis, or possibly even go unnoticed. Infants and young children often have the “sniffles” and it could be mistaken as a simple cold. Some children who initially become infected with EBV later develop mononucleosis in their teenage or young adult life.  

After the initial infection, EBV settles into one’s lymphocytes and lining of the throat and nasal cavity to remain for life. Under normal physiologic circumstances, it is a latent or dormant parasite that does no harm.

Over 95% of adults will test positive for low levels of IgG antibodies, decades after their initial contact with EBV during childhood. When chronic pain patients are tested, autoimmunity is suspected if IgG antibodies are above normal levels found in the great majority of adults.

Once EBV has settled into lymphocytes or the throat lining and becomes dormant, it is living a harmless, symbiotic, parasitic life with its human host.  It will remain in this state, unless the body undergoes some kind of stress, usually trauma or an infection, that lowers or degrades the body's innate or natural immunologic protection systems. 

At this time, the virus may vacate its dormant or latent state to begin what is called a "lytic" or duplicative state.  The term used to indicate this state is "reactivation," meaning that the virus is again active, and attacking and invading new tissues. 

Once reactivated, EBV may create an autoimmune state by altering genes or by developing what is called an auto-antibody that will attack tissues.  In either case, an autoimmune state has been created that attacks normal tissues to produce inflammation, adhesions, scarring, and pain. 

Lymphocytes infected with reactivated EBV may enter any number of tissues. They may cross the blood brain barrier, enter the spinal cord and brain, and attack tissues such as the cauda equina, arachnoid membrane, intervertebral discs, and glial cells. This is the pathologic process in which EBV reactivation may cause chronic pain.

It is likely that entry and invasion of spinal canal and brain tissues may be responsible for the autoimmune manifestations seen after a stroke, head trauma, or complex regional pain syndrome (CRPS).  EBV may also be a cause of centralized pain that is associated with over-sensitization, hyperalgesia, and intractable pain.  There are reports that such common chronic pain conditions as fibromyalgia, small fiber neuropathy, and some arthropathies are caused by EBV autoimmunity.

This article's major intent is to inform all concerned parties that deal with chronic pain that EBV is not just some virus that causes the "kissing disease." It is a new revelation that compels an understanding and awareness that has the distinct potential to improve the plight of chronic pain patients. 

Laboratories and clinical researchers, including this author, are scurrying to identify more diagnostic, treatment, and preventive measures for EBV-caused autoimmunity. I'm pleased to report that our EBV project has been able to identify some initial testing and treatment measures which appear to be effective and a good start in dealing with EBV autoimmunity.  We will share our findings in future articles.

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 this research should visit the Tennant Foundation’s website, Arachnoiditis Hope. You can subscribe to its bulletins here.

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

Can Naproxen Help You Live Longer?

By Pat Anson, PNN Editor

There may be a hidden benefit to the pain reliever naproxen. The non-steroidal anti-inflammatory drug (NSAID) is primarily used to treat arthritis, muscle aches and joint pain, but might also give a boost to your life expectancy, according to the results of a preliminary study.

An international research team analyzed 12-years of health records for over 500,000 people enrolled in the UK Biobank study to see if prescription drugs taken for at least 3 months were associated with higher or lower death rates. Over 400 medications were studied, with patients who were prescribed the drugs compared to control groups that didn’t take them.

“As expected, most drugs harbor a negative effect on lifespan, probably due to the underlying negative effect of the disease the drug is intended for. Importantly, a few drugs seem to have a beneficial effect on lifespan,” wrote lead author Alejandro Ocampo, PhD, a professor at the University of Lausanne and CEO of Epiterna, a Swiss company studying ways to slow the ageing process.        

Ocampo and his colleagues identified four medications associated with lower death rates:

• Naproxen   

• Atorvastatin (a statin)

• Estradiol (female hormone replacement)

• Sildenafil (Viagra)

Statins have long been known to reduce the risk of heart attack and stroke, while estradiol lowers the risk of osteoporosis and bone fractures in post-menopausal women. Sildenafil is well known for treating erectile dysfunction, but also improves cardiovascular health and may even protect against Alzheimer's disease. It’s easy to see how those drugs might increase life expectancy.

The inclusion of naproxen is a bit of a surprise. The active ingredient in Aleve and other over-the-counter pain relievers, naproxen raises the risk of a heart attack, stroke or internal bleeding when taken in high doses or used long-term. High doses of naproxen in 250mg and 500mg tablets are available by prescription, which is what people in the study were taking.

Even at those high doses, researchers found that naproxen was associated with a 10% lower death rate when compared to people who didn’t take the drug. The protective effect was strongest for men on naproxen, who had mortality rates that were 13% lower.

The findings are preliminary, have not been peer-reviewed, and don’t establish a cause-and-effect relationship. We don’t know why or how naproxen helps people live longer, only that it’s associated with a longer lifespan.  

Interestingly, the research team found that two other pain relievers – morphine and paracetamol (acetaminophen) – are associated with shorter lifespans. Again, this may have more to do with the underlying conditions the drugs were prescribed for, rather than the medications themselves.

Ocampo says more research and clinical studies are needed to get a better understanding of the long-term harms and benefits of medication.

“The benefit on lifespan observed for several drugs in this retrospective study could only be truly determined by performing randomized controlled trials. Such studies would aim at treating a healthy aging population with a drug during a sufficiently long follow-up to be able to observe the effect on all-cause mortality,” Ocampo wrote.

If the life expectancy benefits are proven, researchers say it could result in some drugs being “repurposed” as anti-aging treatments for otherwise healthy older adults.

Can Two Questions Identify ‘High Risk’ Pain Patients?

By Pat Anson, PNN Editor

“Have you ever felt your pain is terrible and it's never going to get any better?”

“Have you ever used an illegal drug or prescription medication for non-medical reasons?”

If you answered yes to both questions, you’d be considered at high risk of a “poor pain outcome” at Duke University’s Health System. You’d also be invited into a specialized pain management program that takes a more holistic approach to pain treatment.

Duke’s Integrated Pain and Wellness (IPW) Program was launched in 2019 to identify and treat pain patients at high risk of long-term opioid use, which can result in more frequent and costly visits to hospitals and emergency rooms. It’s one of several efforts in recent years aimed at identifying high risk patients, such as the controversial analytical software used by NarxCare or the far simpler Opioid Risk Tool survey.

Many pain patients feel stigmatized by these risk assessments, and feel they’ve been weaponized solely to deny them treatment with opioids.   

The IPW program is a little different. Patients are encouraged – but not required – to reduce their use of opioids, try non-opioid treatments, and undergo behavioral health therapies to help them learn how to accept their pain without being obsessed by it.     

“Our goal was to establish a comprehensive, integrated approach to pain management that prioritizes early intervention, reduces the dependency on opioids by providing alternative pain management strategies, and decreases the utilization of acute care resources,” wrote Padma Gulur, MD, a Professor in Anesthesiology and Population Health Sciences at Duke University School of Medicine. 

Gulur and her colleagues assessed how 432 patients at the highest risk of poor pain outcomes did after being enrolled in the IPW program.  

Their findings, published in NEJM Catalyst, show that about half the patients (224) reduced their opioid use within 30 days, while a small number (50) increased their opioid use. 

The average improvement in self-reported pain scores was modest (from 6.56 down to 6.11), as were minor improvements in physical function, anxiety, depression and fatigue.  

There were more robust signs of the IPW program’s success in reducing healthcare utilization, with emergency room visits falling by 26% and hospital admissions declining by 43% among the high-risk patients. 

“This approach led to marked patient improvements in both physical and psychological health outcomes,” Gulur said. "By demonstrating the effectiveness of early identification and intervention for patients at risk of poor pain outcomes, this research can inform the development of new therapies and treatment approaches focused on prevention.” 

One hurdle that remains is getting more patients to participate. Of the 13,561 patients who answered “yes” to both questions in the high-risk assessment, less than 11% accepted a referral into the IPW program. Researchers say many were already being treated at pain clinics outside Duke Health and declined to participate.

Toxic Stress Can Lead to Chronic Illness

By Dr. Lawson Wulsin  

COVID-19 taught most people that the line between tolerable and toxic stress – defined as persistent demands that lead to disease – varies widely. But some people will age faster and die younger from toxic stressors than others.

So how much stress is too much, and what can you do about it?

I’m a psychiatrist specializing in psychosomatic medicine, which is the study and treatment of people who have physical and mental illnesses. My research is focused on people who have psychological conditions and medical illnesses as well as those whose stress exacerbates their health issues.

I’ve spent my career studying mind-body questions and training physicians to treat mental illness in primary care settings. My forthcoming book is titled “Toxic Stress: How Stress is Killing Us and What We Can Do About It.”

A 2023 study of stress and aging over the life span – one of the first studies to confirm this piece of common wisdom – found that four measures of stress all speed up the pace of biological aging in midlife. It also found that persistent high stress ages people in a comparable way to the effects of smoking and low socioeconomic status, two well-established risk factors for accelerated aging.

Good Stress vs. Toxic Stress

Good stress – a demand or challenge you readily cope with – is good for your health. In fact, the rhythm of these daily challenges, including feeding yourself, cleaning up messes, communicating with one another and carrying out your job, helps to regulate your stress response system and keep you fit.

Toxic stress, on the other hand, wears down your stress response system in ways that have lasting effects, as psychiatrist and trauma expert Bessel van der Kolk explains in his bestselling book “The Body Keeps the Score.”

The earliest effects of toxic stress are often persistent symptoms such as headache, fatigue or abdominal pain that interfere with overall functioning. After months of initial symptoms, a full-blown illness with a life of its own – such as migraine headaches, asthma, diabetes or ulcerative colitis – may surface.

When we are healthy, our stress response systems are like an orchestra of organs that miraculously tune themselves and play in unison without our conscious effort – a process called self-regulation. But when we are sick, some parts of this orchestra struggle to regulate themselves, which causes a cascade of stress-related dysregulation that contributes to other conditions.

For instance, in the case of diabetes, the hormonal system struggles to regulate sugar. With obesity, the metabolic system has a difficult time regulating energy intake and consumption. With depression, the central nervous system develops an imbalance in its circuits and neurotransmitters that makes it difficult to regulate mood, thoughts and behaviors.

Though stress neuroscience in recent years has given researchers like me new ways to measure and understand stress, you may have noticed that in your doctor’s office, the management of stress isn’t typically part of your treatment plan.

Most doctors don’t assess the contribution of stress to a patient’s common chronic diseases such as diabetes, heart disease and obesity, partly because stress is complicated to measure and partly because it is difficult to treat. In general, doctors don’t treat what they can’t measure.

1 in 5 Americans Live with Toxic Stress

Stress neuroscience and epidemiology have also taught researchers recently that the chances of developing serious mental and physical illnesses in midlife rise dramatically when people are exposed to trauma or adverse events, especially during vulnerable periods such as childhood.

Over the past 40 years in the U.S., the alarming rise in rates of diabetes, obesity, depression, PTSD, suicide and addictions points to one contributing factor that these different illnesses share: toxic stress.

Toxic stress increases the risk for the onset, progression, complications or early death from these illnesses.

Because the definition of toxic stress varies from one person to another, it’s hard to know how many people struggle with it. One starting point is the fact that about 16% of adults report having been exposed to four or more adverse events in childhood. This is the threshold for higher risk for illnesses in adulthood.

Research dating back to before the COVID-19 pandemic also shows that about 19% of adults in the U.S. have four or more chronic illnesses. If you have even one chronic illness, you can imagine how stressful four must be.

And about 12% of the U.S. population lives in poverty, the epitome of a life in which demands exceed resources every day. For instance, if a person doesn’t know how they will get to work each day, or doesn’t have a way to fix a leaking water pipe or resolve a conflict with their partner, their stress response system can never rest. One or any combination of threats may keep them on high alert or shut them down in a way that prevents them from trying to cope at all.

Add to these overlapping groups all those who struggle with harassing relationships, homelessness, captivity, severe loneliness, living in high-crime neighborhoods or working in or around noise or air pollution. It seems conservative to estimate that about 20% of people in the U.S. live with the effects of toxic stress.

Recognizing and Managing Stress

The first step to managing stress is to recognize it and talk to your primary care clinician about it. The clinician may do an assessment involving a self-reported measure of stress.

The next step is treatment. Research shows that it is possible to retrain a dysregulated stress response system. This approach, called “lifestyle medicine,” focuses on improving health outcomes through changing high-risk health behaviors and adopting daily habits that help the stress response system self-regulate.

Adopting these lifestyle changes is not quick or easy, but it works.

The National Diabetes Prevention Program, the Ornish “UnDo” heart disease program and the U.S. Department of Veterans Affairs PTSD program, for example, all achieve a slowing or reversal of stress-related chronic conditions through weekly support groups and guided daily practice over six to nine months. These programs help teach people how to practice personal regimens of stress management, diet and exercise in ways that build and sustain their new habits.

There is now strong evidence that it is possible to treat toxic stress in ways that improve health outcomes for people with stress-related conditions. The next steps include finding ways to expand the recognition of toxic stress and, for those affected, to expand access to these new and effective approaches to treatment.

Lawson R. Wulsin, MD, is a Professor of Psychiatry and Family Medicine at University of Cincinnati. He also practices psychiatry in primary care settings, specializing in psychosomatic medicine.

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