Most Americans Losing Sleep Due to Pain

By Pat Anson, PNN Editor

Does pain keep you awake at night? A new survey found that a surprising number of Americans are unable to get a full night’s sleep because of “painsomnia.”

Almost 98% of U.S. adults surveyed by the Sleep Foundation say they experience pain at least one night a week. About 85% said pain costs them at least two hours of sleep each night, with the average respondent losing six hours of sleep per week.  

Back pain was the most common reason for painsomnia (56%), followed by neck pain (41%), head pain (32%) and knee pain (29%).

“Pain does not have to be extreme to keep us awake,” says Alex Dimitriu, MD, founder of Menlo Park Psychiatry and Sleep Medicine, and a member of the Sleep Foundation's medical-review board. “Even milder forms of pain can result in varying degrees of insomnia, resulting in trouble falling or staying asleep.”

Adults who live with pain average just 6.7 hours of sleep per night, below the recommended 7 to 9 hours. A recent meta-analysis of 31 studies found that sleep loss increases our perception of pain and creates a vicious cycle. Poor sleep leads to more pain and vice versa.

“When you can’t sleep well due to pain, this leads to more pain,” said Medhat Mikhael, MD, a pain management specialist and medical director of the Spine Health Center at Orange Coast Medical Center in Fountain Valley, CA. “You also become anxious about not sleeping enough, so you don’t sleep. Then you’re fatigued, so you feel a lot more pain.”

When asked to rate their pain on a zero to ten scale, 73% of respondents with chronic pain said their nightly pain was at level 5 or higher. Over half (57%) said they wake up at least three times during the night, and 41% say they wake up earlier than they’d like.  Experts say fitful sleeping is less restorative and heightens pain sensitivity.

“Sleep is as much about quality as it is about quantity,” Dimitriu says. “Falling asleep too late can push circadian rhythms into a delayed sleep-phase cycle. And waking too early can result in an advanced sleep phase cycle, where you get tired too early in the evening.”

What are people doing about their poor sleep? Over half of respondents (56%) who lose sleep to pain have taken sleep aids in the past month. Melatonin was the most popular (49%), followed by Benadryl (diphenhydramine) (23%).

A surprising number said connecting with others in pain support groups helps them sleep. Although only 1 in 5 pain sufferers say they’ve participated in support groups, 91% of those who did say interacting with other painsomniacs helped them learn how to better manage, understand or improve their sleep.

This Sleep Foundation survey was conducted online in June, 2022. Results are from 1,250 participants aged 18 and older who lived in the United States.

Widely Used Red Food Dye Linked to IBD

By Pat Anson, PNN Editor

Allura Red is one of the most widely used artificial food dyes in the world. Also known as “Red Dye 40,” the dark red coloring is added to sodas, candies, breakfast cereals, condiments and dozens of other food products to make them more appetizing.

Over the years, Allura Red has been linked to a variety of different health conditions, including attention deficit hyperactivity disorder (ADHD) in children. Now there is emerging evidence that Allura Red may also trigger inflammatory bowel diseases (IBDs) such as Crohn’s and ulcerative colitis.

Researchers at McMaster University in Ontario, Canada exposed laboratory mice to Allura Red for 12 weeks — at about the same levels humans might consume — and found that it caused chronic inflammation in their gastrointestinal tracts and raised levels of serotonin, a hormone that affects mood and digestion.

“This study demonstrates significant harmful effects of Allura Red on gut health and identifies gut serotonin as a critical factor mediating these effects. These findings have important implication in the prevention and management of gut inflammation,” McMaster researcher Waliul Khan, PhD, said in a statement.

“What we have found is striking and alarming, as this common synthetic food dye is a possible dietary trigger for IBDs. This research is a significant advance in alerting the public on the potential harms of food dyes that we consume daily.”

Although Allura Red and eight other synthetic food dyes – all derived from petroleum -- are considered “safe for the general population” by the FDA, there have been relatively few studies of their effect on human health. Some experts believe the dyes disrupt the absorption of key minerals like zinc and iron, causing hyperactivity, allergic reactions and gut inflammation.

STRAWBERRY SODA CONTAINING ALLURA RED DYE

Recent research has helped establish the importance of gut health, and that bacteria can have profound effects – both harmful and beneficial -- on our immune and gastrointestinal systems. A 2022 study, for example, found evidence that a particular strain of bacteria causes abdominal pain, cramps, bloating, gas and diarrhea – symptoms common to IBD. A 2019 study linked gut bacteria to fibromyalgia.

Western diets that have a lot of processed food rich in fat, meat and sugar have also been linked to gut inflammation. Processed foods tend to have a lot of Allura Red and other chemical additives, and Khan believes they warrant further study.

“The literature suggests that the consumption of Allura Red also affects certain allergies, immune disorders and behavioural problems in children, such as attention deficit hyperactivity disorder,” said Khan, a professor of Pathology and Molecular Medicine at McMaster and principal investigator at the Farncombe Family Digestive Health Research Institute.

Khan and his colleagues published their findings in Nature Communications. Their study was funded by the Canadian Institutes of Health Research.

Persistent Pain Worsens Physical Function and Mental Health in Seniors

By Pat Anson, PNN Editor

Having persistent pain in your senior years is very common and contributes to declines in physical function and mental health, according to large new study that calls for more proactive treatment of pain in older adults.

“The findings from this study point to the importance of access to effective treatment for persistent pain in older adults and the need for additional research in chronic pain to optimize quality of life,” said lead author Christine Ritchie, MD, Director of the Mongan Institute Center for Aging and Serious Illness at Massachusetts General Hospital.

Ritchie and her colleagues analyzed health data for nearly 5,600 Medicare beneficiaries aged 65 and older who participated in the National Health Aging Trends Study from 2011 to 2019. Nearly 39% of participants reported having “persistent pain” and almost 28% had “intermittent pain.”  Only about a third of older adults (33.5%) reported having no “bothersome pain.”

Researchers found that seniors with persistent pain were more likely to report depression and anxiety, and to have three or more comorbid conditions such as a heart attack, stroke or cancer than those with intermittent or no pain. They were also more likely to have lower scores for mood and self-care activities such as eating, hygiene and dressing.

Perhaps the only good news is that differences were not found in cognitive impairment or dementia between those with and without persistent pain.

“This study is the first to include a representative sample of older Americans that demonstrates meaningful declines in physical function and well-being among those with persistent pain,” researchers reported in the Journal of the American Geriatrics Society.

“Given the high prevalence of persistent pain and its negative effects on both function and well-being, domains of the lived experience highly valued by older adults, it is incumbent on clinicians to prioritize strategies to effectively address their persistent pain.”

The researchers said many older adults lack access to effective nonpharmacological therapies and receive little guidance from primary care physicians about pain treatments.

Participants with persistent pain were more likely to be female, low-income, have limited education, and to be living alone – findings that mirror those of a 2020 study that found less-educated, working class Americans had higher rates of pain, social isolation, drug abuse, disability and suicide.  

A recent study in the UK found that having chronic pain in middle age significantly raises the chances of having pain and poor overall health in your senior years.

Hypermobility Linked to Depression and Anxiety at Young Age

By Madora Pennington, PNN Columnist

The teenage years are difficult for almost everyone, but even more so for teens with hypermobile joints, a condition known as hypermobility. Their joints have an excess range of motion, and some can literally bend their arms, legs and fingers backward.

Jess — who asked that we not use her last name — had always noticed she was extremely flexible. By the time she was a teenager, Jess had crushing fatigue and anxiety. She obsessed over her grades like a perfectionist and developed an eating disorder. Her terrible anxiety caused her to self-medicate, as she did all she could to keep up with her peers.

Eventually, it all became too much. Jess had to leave high school and finish her degree through proficiency testing. Not until age 19 was she finally diagnosed with Ehlers-Danlos Syndrome (EDS), a disease that weakens connective tissue in the joints and causes hypermobility.

Hypermobility in early life is normal. All babies and children are highly flexible, which most eventually outgrow. But for some children, hypermobility is permanent. Excessively loose joints are a feature common to many inherited disorders like EDS, wherein the body cannot make connective tissue that is stable and strong. In essence, the "glue" holding their bodies together is flawed and weak.

Extremely flexible people like Jess may be seen by their peers as having interesting or cool skills, like doing contortionist tricks or excelling in yoga. But hypermobility is a severe health problem that can lead to mental health issues.

"Hypermobility affects one in four people in the UK. Like other musculoskeletal conditions, it can have a profound and far-reaching impact on life, causing daily pain, fatigue and often disrupted sleep," says Dr. Neha Issar-Brown, Director of Research and Health Intelligence at the UK-based charity Versus Arthritis. "Previous studies in adults have shown that you are more likely to suffer from anxiety if you have hypermobility, and that the daily toll of painful symptoms can lead to depression.”

A new study in BMJ Open found a similar link in adolescents. To see if there is an association between hypermobility, anxiety and depression in late adolescence, researchers at Brighton and Sussex Medical School evaluated over 14,000 teens with joint hypermobility.

At age 14, their hypermobility was scored, which is done by measuring the degree to which various joints hyperextend or bend past the point where they should. Then, at age 18, the participants answered surveys about depression and anxiety. Pain, a common complication of hypermobility, was also taken into account. The participants' heart rates were also studied.

"Many psychiatric problems, including depression and anxiety, start before the age of 25. It is therefore important to identify the factors that may increase the risk for these disorders. Being aware of the link between hypermobility and depression and anxiety means that we can work on developing appropriate and effective treatments," said lead author Dr. Jessica Eccles, Department of Neuroscience, Brighton and Sussex Medical School.

Eccles and her colleagues found that young people with joint hypermobility were more likely to have depression and anxiety, and their psychiatric symptoms were also more severe. Joint hypermobility was more common in females than males, but it was only among males that hypermobility increased the risk for depression.

"This study has highlighted the need for more targeted and bespoke support for hypermobile teenagers, particularly girls," says Lea Milligan, CEO of the UK-based advocacy organization MK Mental Health Research. "The findings don't just show the need for support for this group of individuals, but also demonstrate the importance of research that takes a whole mind, body brain approach to health and uses longitudinal studies to improve our understanding of which demographics are at higher risk of depression and anxiety.”

Why hypermobile people suffer from more psychopathologies may be due to a dysregulation of the nervous system called dysautonomia, which is very common among those with loose joints. Their poorly regulated nervous systems cause a rapid increase in heart rate when they rise to stand, when it should remain constant. This inability of the body to maintain a smooth and consistent heart rate when posture changes has also been associated with anxiety.

Rapid heart rates and poor cardiovascular regulation also occur when someone has anxiety and depression. The higher a person's resting heart rate, the more psychological symptoms tend to follow. Those with depression tend to have different skin temperatures, breathing rates, and a lower variability in heart rate.

Complaints from UK parents with hypermobile children motivated this study. They encountered healthcare providers that were ignorant of the complications and challenges of hypermobility and dismissed their concerns. More awareness and education are needed to help these families, and this study is a step in that direction.

Madora Pennington is the author of the blog LessFlexible.com about her life with Ehlers-Danlos Syndrome. She graduated from UC Berkeley with minors in Journalism and Disability Studies. 

Should Older Adults Risk Major Surgery?

By Judith Graham, Kaiser Health News

Nearly 1 in 7 older adults die within a year of undergoing major surgery, according to an important new study that sheds much-needed light on the risks seniors face when having invasive procedures.

Especially vulnerable are older patients with probable dementia (33% die within a year) and frailty (28%), as well as those having emergency surgeries (22%). Advanced age also amplifies risk: Patients who were 90 or older were six times as likely to die than those ages 65 to 69.

The study in JAMA Surgery, published by researchers at Yale School of Medicine, addresses a notable gap in research: Though patients 65 and older undergo nearly 40% of all surgeries in the U.S., detailed national data about the outcomes of these procedures has been largely missing.

“As a field, we’ve been really remiss in not understanding long-term surgical outcomes for older adults,” said Dr. Zara Cooper, a professor of surgery at Harvard Medical School and the director of the Center for Geriatric Surgery at Brigham and Women’s Hospital in Boston.

Of particular importance is information about how many seniors die, develop disabilities, can no longer live independently, or have a significantly worsened quality of life after major surgery.

“What older patients want to know is, ‘What’s my life going to look like?’” Cooper said. “But we haven’t been able to answer with data of this quality before.”

In the new study, Dr. Thomas Gill and Yale colleagues examined claims data from traditional Medicare and survey data from the National Health and Aging Trends study spanning 2011 to 2017. (Data from private Medicare Advantage plans was not available at that time but will be included in future studies.)

Invasive procedures that take place in operating rooms with patients under general anesthesia were counted as major surgeries. Examples include procedures to replace broken hips, improve blood flow in the heart, excise cancer from the colon, remove gallbladders, fix leaky heart valves, and repair hernias, among many more.

More Complications

Older adults tend to experience more problems after surgery if they have chronic conditions such as heart or kidney disease; if they are already weak or have difficulty moving around; if their ability to care for themselves is compromised; and if they have cognitive problems, noted Gill, a professor of medicine, epidemiology, and investigative medicine at Yale.

Two years ago, Gill’s team conducted research that showed 1 in 3 older adults had not returned to their baseline level of functioning six months after major surgery. Most likely to recover were seniors who had elective surgeries for which they could prepare in advance.

In another study, published last year in the Annals of Surgery, his team found that about 1 million major surgeries occur in individuals 65 and older each year, including a significant number near the end of life. Remarkably, data documenting the extent of surgery in the older population has been lacking until now.

“This opens up all kinds of questions: Were these surgeries done for a good reason? How is appropriate surgery defined? Were the decisions to perform surgery made after eliciting the patient’s priorities and determining whether surgery would achieve them?” said Dr. Clifford Ko, a professor of surgery at UCLA School of Medicine and director of the Division of Research and Optimal Patient Care at the American College of Surgeons.

As an example of this kind of decision-making, Ko described a patient who, at 93, learned he had early-stage colon cancer on top of preexisting liver, heart, and lung disease. After an in-depth discussion and being told that the risk of poor results was high, the patient decided against invasive treatment.

“He decided he would rather take the risk of a slow-growing cancer than deal with a major operation and the risk of complications,” Ko said.

Still, most patients choose surgery. Dr. Marcia Russell, a staff surgeon at the Veterans Affairs Greater Los Angeles Healthcare System, described a 90-year-old patient who recently learned he had colon cancer during a prolonged hospital stay for pneumonia.

“We talked with him about surgery, and his goals are to live as long as possible,” said Russell. To help prepare the patient, now recovering at home, for future surgery, she recommended he undertake physical therapy and eat more high-protein foods, measures that should help him get stronger.

“He may need six to eight weeks to get ready for surgery, but he’s motivated to improve,” Russell said.

Not Enough Surgeons

The choices older Americans make about undergoing major surgery will have broad societal implications. As the 65-plus population expands, “covering surgery is going to be fiscally challenging for Medicare,” noted Dr. Robert Becher, an assistant professor of surgery at Yale and a research collaborator with Gill. Just over half of Medicare spending is devoted to inpatient and outpatient surgical care, according to a 2020 analysis.

What’s more, “nearly every surgical subspecialty is going to experience workforce shortages in the coming years,” Becher said, noting that in 2033, there will be nearly 30,000 fewer surgeons than needed to meet expected demand.

These trends make efforts to improve surgical outcomes for older adults even more critical. Yet progress has been slow. The American College of Surgeons launched a major quality improvement program in July 2019, eight months before the covid-19 pandemic hit. It requires hospitals to meet 30 standards to achieve recognized expertise in geriatric surgery. So far, fewer than 100 of the thousands of hospitals eligible are participating.

One of the most advanced systems in the country, the Center for Geriatric Surgery at Brigham and Women’s Hospital, illustrates what’s possible. There, older adults who are candidates for surgery are screened for frailty. Those judged to be frail consult with a geriatrician, undergo a thorough geriatric assessment, and meet with a nurse who will help coordinate care after discharge.

Also initiated are “geriatric-friendly” orders for post-surgery hospital care. This includes assessing older patients three times a day for delirium (an acute change in mental status that often afflicts older hospital patients), getting patients moving as soon as possible, and using non-narcotic pain relievers. “The goal is to minimize the harms of hospitalization,” said Cooper, who directs the effort.

She told me about a recent patient, whom she described as a “social woman in her early 80s who was still wearing skinny jeans and going to cocktail parties.” This woman came to the emergency room with acute diverticulitis and delirium; a geriatrician was called in before surgery to help manage her medications and sleep-wake cycle, and recommend non-pharmaceutical interventions.

With the help of family members who visited this patient in the hospital and have remained involved in her care, “she’s doing great,” Cooper said. “It’s the kind of outcome we work very hard to achieve.”

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

How Racial and Ethnic Disparities Affect Pain

By Madora Pennington, PNN Columnist

Much of the race-related research on chronic pain in the United States only compares Black and White Americans, leaving out many other ethnic groups and demographics.  

In an attempt to broaden our understanding of who experiences pain and why, researchers culled through eight years of public surveys conducted by the CDC and the U.S. Census Bureau from 2010 to 2018. These National Health Interview Surveys gathered information from White, Black, Hispanic, Asian, Native American and multiracial Americans, giving us new insight into the role of race in pain prevalence. 

“People often tend to think about pain as a personal issue or personal struggle, but it’s really a broad social and societal issue,” says Anna Zajacova, PhD, a sociology professor at the University of Western Ontario and lead author of Beyond Black vs White, a study recently published in the journal PAIN.       

In addition to race, Zajacova and her colleagues looked at socioeconomic factors such as education, family income, home ownership and whether someone was born in the U.S. or abroad.  They found that racial disparities in pain are far larger than previously recognized, with Native Americans nearly five times more likely to have severe pain than Asian Americans. Hispanics, Whites and Blacks fell between the two extremes.

Severe Pain Prevalence

• 2.4% Asian Americans

• 5.0% Hispanics

• 6.8% Whites

• 7.6% Blacks

• 8.7% Multiracial Adults

• 11.1% Native Americans

Why is there so much disparity between races? Researchers found that Asian Americans collectively had the highest levels of education and family income, giving them a socioeconomic advantage that may explain their lower pain prevalence. Native Americans, on the other hand, tend to be the most socioeconomically disadvantaged ethnic group, which is likely a factor in their high pain prevalence.

“We really need to understand what is causing the high pain among Native American and multiracial adults, and what factors protect Asian Americans from reporting high pain on average. This question will require delving into upstream causes such as discrimination, resulting stress and corollary health impacts, as well as the role of protective factors such as community and individual resilience,” Zajacova told PNN. 

While socioeconomic factors play a role, they're not always a deciding one. Hispanics reported less severe pain than White Americans despite having fewer socioeconomic advantages, indicating that other factors may be involved.

One may be place of birth. Researchers found that immigrants reported significantly less pain than native-born adults. Since about half of Hispanic adults are foreign born, that may help explain their lower incidence of pain -- or at least a reluctance to report it. 

Researchers say we need a better understanding of the racial, ethnic, social and economic issues that contribute to chronic pain if we ever hope to manage it.   

“The biopsychosocial model of pain predicts that people marginalized by social conditions would experience more pain. Our foundational results show more nuanced patterns, in which some minoritized groups show higher pain prevalence than Whites, whereas others show lower prevalence,” Zajacova wrote.

“Given that pain is arguably the most prevalent and costly public health condition in the United States, enhanced knowledge of racial and ethnic disparities in pain is urgently needed to inform policy decisions and focus efforts at population-level prevention and intervention.” 

Madora Pennington is the author of the blog LessFlexible.com about her life with Ehlers-Danlos Syndrome. She graduated from UC Berkeley with minors in Journalism and Disability Studies. 

‘Promising Results’ for Low-Dose Naltrexone as Pain Reliever

By Pat Anson, PNN Editor

Low-dose naltrexone (LDN) continues to get more recognition from the medical community as a treatment for some types of chronic pain.

In a review of 47 studies on the off-label use of LDN, researchers at the University of Kansas Medical Center found “promising results” that naltrexone improves pain and function and reduces symptom severity in patients with chronic inflammatory or centralized pain. Most of the studies were small, however, and larger clinical trials are needed to demonstrate LDN’s efficacy.

“Though the results look promising, further, more well controlled studies are required before formal recommendations can be made,” said lead author Adam Rupp, DO, who will present his findings this week at the annual meeting of the American Society of Regional Anesthesia and Pain Medicine (ASRA) in Orlando, Florida.

Naltrexone is an inexpensive generic drug that is only approved by the Food and Drug Administration as a treatment for substance abuse. In 50mg doses, naltrexone blocks opioid receptors in the brain and decreases the desire to take opiates or alcohol.  

But in smaller doses of 5mg or less, patients with fibromyalgia, interstitial cystitis, intractable pain and other chronic conditions have found LDN to be an effective pain reliever. But because LDN is prescribed “off label” for pain, much of the evidence supporting LDN is anecdotal.

How naltrexone works is not entirely clear, but LDN supporters believe the drug helps modulate the immune system, reducing inflammation and stimulating the production of endorphins, the body's natural painkiller. LDN is not recommended for people currently taking opioid medication because it blocks opioid receptors and may cause withdrawal.

In their literature review, Rupp and his colleagues found that LDN improved physical function, sleep, mood, fatigue and quality of life in patients with Complex Regional Pain Syndrome (CRPS), fibromyalgia, diabetic neuropathy, Crohn’s disease, rheumatoid arthritis and low back pain. In patients with Crohn’s, improvements were also noted in the colon’s appearance during colonoscopies.

Side effects from LDN were minimal, consisting most commonly of vivid dreams, headaches, diarrhea and nausea. Most of the side effects resolved with continued use of LDN.

“The evidence in this review provides support for the off-label use of LDN for various chronic
inflammatory or centralized pain conditions. However, it is apparent that high-quality controlled studies focusing on administration, dosing and follow up time are needed before formal recommendations can be made,” Rupp said.

“Despite the current paucity of high-quality evidence in the literature, LDN continues to offer promising results in the management of symptoms in patients with chronic inflammatory or centralized pain conditions.”

Because LDN is not recommended as a pain treatment by the FDA or professional medical societies, patients interested in trying it often encounter doctors who refuse to prescribe it or don’t know anything about it. The LDN Research Trust includes a list of LDN-friendly doctors and pharmacies on its website.

Restoring Blood Flow Reduces Pain in Patients with Peripheral Artery Disease

By Pat Anson, PNN Editor

Restoring blood flow to the legs significantly reduces pain and improves quality of life for people with peripheral artery disease (PAD), according to new research presented this week at the American Heart Association’s Scientific Sessions in Chicago.

Over 200 million people worldwide suffer from PAD -- a narrowing of peripheral arteries throughout the body that can cause severe leg pain, cramping and fatigue after a short walk or even just climbing a flight of stairs. In one out of ten people with PAD, the lack of blood flow can lead to chronic limb-threatening ischemia (CLTI), where people experience pain even when resting. Left untreated, tissue damage in the leg may result in amputation.

To restore blood flow, a common treatment for PAD is leg bypass surgery, in which a passage around the blocked arteries is created by using another vein from the leg of a patient. A less invasive approach is angioplasty, in which a balloon-tipped catheter is inserted into the blocked artery to widen it. A stent is then often placed to keep the artery open.

Few studies have compared the effectiveness of bypass surgery to angioplasty and stenting, which are known as “endovascular” procedures.

“The large body of high-quality evidence that guides treatment of heart disease and stroke does not exist for PAD, and until now, there has been almost no data to inform the care of CLTI patients,” says lead author Matthew Menard, MD, an associate professor of surgery at Harvard Medical School, and co-director of endovascular surgery at Brigham and Women’s Hospital.

In the first large-scale randomized controlled study of its kind, Menard and his colleagues enrolled 1,830 people with severe PAD at 150 centers in the U.S., Canada, Italy, Finland and New Zealand. Participants were surveyed at the beginning of the study about their quality of life and at several follow-up visits for 4 years after their surgery or procedure. The surveys asked about pain, PAD symptoms and severity, physical activity and mental health.

Pain levels were high and quality-of-life scores were low at the beginning of the study, reflecting the poor health and well-being of many patients with CLTI. But after surgery or an endovascular procedure, pain scores decreased significantly and quality-of-life scores improved for all participants.

“Improvement in health-related quality-of-life measures regardless of the type of procedure is very encouraging and highlights the importance of timely restoration of blood flow to the leg and foot,” said Menard.

Menard noted there were some differences initially between the two study groups favoring endovascular procedures, possibly reflecting the longer recovery time for a surgical bypass. But the differences were not “clinically meaningful” and leveled out over time.

“The quality-of-life data are a nice complement to the clinical results and suggest that both revascularization strategies may effectively improve a patient’s quality of life. So, while there is still much work to be done, and quality-of-life measures have not always been the focus in past PAD research, this is an important step forward,” he said.

PAD patients who don’t have bypass surgery or endovascular procedures may want to continue walking despite the pain and discomfort, according to a recent study. Researchers at Northwestern University’s Feinberg School of Medicine found that elderly PAD patients who exercised 5 days a week walked at a faster pace and performed better on physical performance tests than non-walkers.

Between 8 and 10 million people in the United States have PAD. The condition disproportionately affects African-Americans, Native Americans and those with low socioeconomic status.

Study Finds Harmful Effects of Chronic Pain Persist Throughout Life

By Pat Anson, PNN Editor

If you have chronic pain in middle age, chances are you will continue to have pain and poor overall health as you enter your senior years, according to a large new study in the UK that found pain has wide-ranging effects throughout life. Pain sufferers are significantly more likely to be unhappy, depressed and unemployed as they grow older.  

Researchers followed the health data and survey responses of over 12,000 people who were born in England, Scotland and Wales in March 1958. The study began in 2003, when most of the respondents were age 44, and continued until they turned 62 in 2021

The research findings, published in PLOS ONE, show that pain can persist for decades and may even be passed from one generation to the next.

“Tracking a birth cohort across their life-course we find chronic pain is highly persistent. It is associated with poor mental health outcomes later in life including depression, as well as leading to poorer general health and joblessness. We hope the study highlights the need for academics and policy makers to focus more attention on the problems of chronic pain,” wrote lead author Alex Bryson, PhD, a Research Fellow at University College London.

Bryson and his colleagues found that two-fifths of respondents reported suffering from chronic pain in their 40’s. Of those, 84% still reported “very severe” pain at age 50. Having chronic pain at 44 was also associated with poor mental health, lower life satisfaction, pessimism about the future, poor sleep and joblessness at age 55.

In the last year of their study, researchers found that having pain at midlife also raises the risk of a covid infection at age 62, a finding that supports previous studies showing that people in poor health are more susceptible to Covid-19.

The study pinpointed several factors that predict pain at a later age, including a father’s social and economic status. Respondents whose fathers were professionals, managers or administrators when they were born were significantly less likely to report chronic pain 44 years later.

The UK study reached many of the same conclusions as U.S. researchers, who have found that less-educated, working class Americans have higher rates of pain, social isolation, drug abuse, disability and suicide than those with college degrees. Efforts at treating physical pain, either with opioids or non-opioid therapies, have failed to turn the tide.  

“Our evidence on the persistence of pain across the life-course suggests efforts to counter it have not been wholly successful,” said Bryson. “We have shown that it is, in part, passed from one generation to the next, with those from lower social classes suffering most. Pain appears to be another source of inter-generational disadvantage, and one that is potentially as problematic as other aspects of social deprivation.”

Newly Discovered Gut Bacteria Linked to Rheumatoid Arthritis

By Meagan Chriswell, University of Colorado Medicine

Rheumatoid arthritis affects 1 in 100 people worldwide. It causes inflamed, painful and swollen joints, often in the hands and wrists, and can lead to loss of joint function as well as chronic pain and joint deformities and damage. What causes this condition has been unknown.

In our recently published study, my colleagues and I found an important clue to a potential culprit behind this disease: the bacteria in your gut.

Rheumatoid arthritis is an autoimmune condition, meaning it develops when the body’s immune system starts to attack itself. Proteins called antibodies, which usually help fight off viruses and bacteria, begin to attack the joints instead.

The origins of the antibodies that cause rheumatoid arthritis have been an area of study for many years. Some research has shown that these antibodies can start forming at sites like the mouth, lung and intestines over 10 years before symptoms arise. But until now, it was unclear why researchers were finding these antibodies in these particular areas.

We wanted to investigate what could trigger the formation of these antibodies. Specifically, we wondered if bacteria in the microbiome, a community of microorganisms that live in the intestines, might be the ones activating the immune response that leads to rheumatoid arthritis.

Since microbes commonly live at the same sites as the antibodies driving rheumatoid arthritis, we hypothesized that these bacteria could be triggering the production of these antibodies. We reasoned that though these antibodies were meant to attack the bacteria, rheumatoid arthritis develops when they spread beyond the intestines to attack the joints.

First, we sought to identify the intestinal bacteria targeted by these antibodies. To do this, we exposed the bacteria in the feces of a subset of people at risk for developing rheumatoid arthritis to these antibodies, allowing us to isolate just the bacterial species that reacted and bound to the antibodies.

We found that one previously unknown species of bacteria was present in the intestines of around 20% of people who were either diagnosed with rheumatoid arthritis or produce the antibodies that cause the disease.

As a member of the Cherokee Nation of Oklahoma, I suggested we name this species Subdoligranulum didolesgii (“didolesgii” means arthritis or rheumatism in Cherokee) as a nod to the contributions that other Indigenous scholars have made to science as well as the fact that rheumatoid arthritis affects Indigenous people at a higher rate than other populations.

Subdoligranulum didolesgii has not been detected in the feces of healthy people before, and it is currently unknown how prevalent this bacteria is in the general population.

We also found that these bacteria can activate specialized immune cells called T cells in people with rheumatoid arthritis. T cells drive inflammatory responses in the body, and have been linked to the development of different autoimmune diseases.

These findings suggest that these gut bacteria may be activating the immune systems of people with rheumatoid arthritis. But instead of attacking the bacteria, their immune system attacks the joints.

Why This Bacteria?

It is still unknown why people with rheumatoid arthritis develop an immune response to Subdoligranulum didolesgii. But we think it may be the culprit when it comes to rheumatoid arthritis because this bacteria is found only in the intestines of people with rheumatoid arthritis, and not in the intestines of healthy people.

While many immune responses happen in the intestines, they are usually self-contained and do not spread to other areas of the body. However, we believe that a particularly strong intestinal immune response against Subdoligranulum didolesgii could allow antibodies to bypass the intestinal “firewall” and spread to the joints.

To confirm our hypothesis, we gave mice an oral dose of Subdoligranulum didolesgii and monitored their reaction. Within 14 days, the mice began to develop joint swelling and antibodies that attacked their joints.

My colleagues and I hope this research can shed light on the origins of rheumatoid arthritis. Our next goal is to discover how common these bacteria are in the general population and test whether the presence of these bacteria in the gut may lead to the development of rheumatoid arthritis in people.

It’s important to note that antibiotics are unlikely to be helpful treatment for the microbiomes of patients with rheumatoid arthritis. Although Subdoligranulum didolesgii may be triggering an autoimmune response for some people with rheumatoid arthritis, antibiotics eliminate both helpful and harmful bacteria in the gut. Additionally, removing the bacteria won’t necessarily stop the immune system from attacking the joints once it has started.

Nevertheless, we believe that these bacteria can be used as tools to develop treatments for rheumatoid arthritis and hopefully ways to prevent disease from happening in the first place.

Meagan Chriswell is a MD/PhD Candidate in Immunology at the University of Colorado Anschutz Medical Campus. She does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article.

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

Brain Changes Found in Patients with Long-Term Lyme Disease

By Pat Anson, PNN Editor

Researchers at Johns Hopkins University have documented changes in the brains of patients with post-treatment Lyme disease that may explain symptoms such as brain fog, memory loss and other cognitive issues. The finding could also have implications for patients with long covid, fibromyalgia, multiple sclerosis, chronic fatigue and other health conditions who have cognitive problems.    

Lyme disease is a bacterial illness spread by ticks that causes a rash, flu-like aches and fever, joint pain and fatigue. Most patients fully recover when treated early with antibiotics, but up to 20% of those with post-treatment Lyme disease (PTLD) have long-term symptoms, including depression, insomnia and cognitive difficulties. There is usually no clinical or laboratory evidence to explain their ongoing issues.

“Objective biologic measures of post-treatment Lyme symptoms typically can’t be identified using regular MRIs, CT scans, or blood tests,” says John Aucott, MD., director of the Johns Hopkins Lyme Disease Clinical Research Center.

Aucott and his colleagues recruited 12 PTLD patients and 18 people without a history of Lyme to undergo functional MRI (fMRI) scans while performing a short-term memory task. The scans allow investigators to track blood flow and other changes in the brain in real time.

Their findings, published in the journal PLOS ONE, suggest that cognitive difficulties in PTLD patients are linked to functional and structural changes in the “white matter” of the brain, which is crucial for processing and relaying information. The imaging tests revealed unusual activity in the frontal lobe, an area of the brain responsible for memory recall and concentration. Patients with post-treatment Lyme needed longer periods of time to complete the memory task.

“We saw certain areas in the frontal lobe under-activating and others that were over-activating, which was somewhat expected,” said lead author Cherie Marvel, PhD, an associate professor of neurology at Johns Hopkins.

“However, we didn’t see this same white matter activity in the group without post-treatment Lyme.”

To confirm their finding, researchers used another form of imaging called diffusion tensor imaging (DTI) on all 12 patients with Lyme and 12 of the non-Lyme participants. DTI detects the direction of water movement within brain tissue. Water was diffusing, or leaking, in the the same white matter regions identified in the fMRI.

Researchers believe the increased activity they saw in white matter may reflect an immune system response in the PTLD patients, which may also explain cognitive issues in patients with other chronic health conditions.

PLOS ONE

“Results reported here may have implications for other diseases in which white matter pathology has been demonstrated (e.g., multiple sclerosis) or in illnesses in which cognitive complaints follow disease onset,” researchers said. “The use of multimodal neuroimaging methods, like the ones used in the current study, may be a viable approach for obtaining information on brain function and structure to identify biomarkers of disease burden.”

Researchers say larger studies with more patients will be needed to confirm their findings, as well as long-term tracking of brain changes from the initial Lyme infection through development of PTLD.

Nearly 500,000 people are believed to get Lyme disease each year in the United States. Diagnoses of Lyme have soared over the past 15 years, according to a recent analysis of insurance claims that found Lyme cases rose 357% in rural areas and 65% in urban areas. The highest rates of Lyme were in New Jersey, Vermont, Maine, Rhode Island and Connecticut.

Experimental Vaccines Target Epstein-Barr Virus

By Liz Szabo, Kaiser Health News

Maybe you’ve never heard of the Epstein-Barr virus. But it knows all about you.

Chances are, it’s living inside you right now. About 95% of American adults are infected sometime in their lives. And once infected, the virus stays with you.

Most viruses, such as influenza, just come and go. A healthy immune system attacks them, kills them, and prevents them from sickening you again. Epstein-Barr and its cousins, including the viruses that cause chickenpox and herpes, can hibernate inside your cells for decades.

This viral family has “evolved with us for millions of years,” said Blossom Damania, a virologist at the University of North Carolina-Chapel Hill. “They know all your body’s secrets.”

Although childhood Epstein-Barr infections are typically mild, exposure in teens and young adults can lead to infectious mononucleosis, a weeks-long illness that sickens 125,000 Americans a year, causing sore throats, swollen glands, and extreme fatigue. And while Epstein-Barr spends most of its time sleeping, it can reawaken during times of stress or when the immune system is off its game. Those reactivations are linked to a long list of serious health conditions, including several types of cancer and autoimmune diseases.

Scientists have spent years trying to develop vaccines against Epstein-Barr, or EBV. But recently several leaps in medical research have provided more urgency to the quest — and more hope for success. In just the past year, two experimental vaccine efforts have made it to human clinical trials.

What’s changed?

First, the Epstein-Barr virus has been shown to present an even greater threat. New research firmly links it to multiple sclerosis, or MS, a potentially disabling chronic disease that afflicts more than 900,000 Americans and 2.8 million people worldwide.

The journal Science in January published results from a landmark 20-year study of 10 million military personnel that offers the strongest evidence yet that Epstein-Barr can trigger MS. The new study found that people infected with Epstein-Barr are 32 times as likely as people not infected to develop MS.

And shedding new light on the mechanisms that could explain that correlation, a separate group of scientists published a study in Nature describing how the virus can cause an autoimmune reaction that leads to MS.

The disease, which usually strikes between ages 20 and 40, disrupts communication between the brain and other parts of the body and is often marked by recurring episodes of extreme fatigue, blurred vision, muscle weakness, and difficulty with balance and coordination. At its worst, MS can lead to impaired speech and paralysis.

“Now that we know that Epstein-Barr is very tightly linked to MS, we could save a lot of lives if we develop the vaccine now.”

— Blossom Damania, Virologist

Amplifying that newfound urgency, several new studies suggest that reactivation of the Epstein-Barr virus also is involved with some cases of long covid, a little-understood condition in which patients experience lingering symptoms that often resemble mononucleosis.

And just as crucial to the momentum: Advances in vaccine science spurred by the pandemic, including the mRNA technology used in some covid vaccines, could accelerate development of other vaccines, including ones against Epstein-Barr, said Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine. Hotez co-created a low-cost, patent-free covid vaccine called Corbevax.

Some researchers question the need for a vaccine that targets a disease like MS that, while debilitating, remains relatively rare.

Eliminating Epstein-Barr would require vaccinating all healthy children even though their risk of developing cancer or multiple sclerosis is small, said Dr. Ralph Horwitz, a professor at the Lewis Katz School of Medicine at Temple University.

Before exposing children to the potential risks of a new vaccine, he said, scientists need to answer basic questions about MS. For example, why does a virus that affects nearly everyone cause disease in a small fraction? And what roles do stress and other environmental conditions play in that equation?

The answer appears to be that Epstein-Barr is “necessary but not sufficient” to cause disease, said immunologist Bruce Bebo, executive vice president for research at the National MS Society, adding that the virus “may be the first in a string of dominoes.”

‘We Could Save a Lot of Lives’

Hotez said researchers could continue to probe the mysteries surrounding Epstein-Barr and MS even as the vaccine efforts proceed. Further study is required to understand which populations might benefit most from a vaccine, and once more is known, Hotez said, such a vaccine possibly could be used in patients found to be at highest risk, such as organ transplant recipients, rather than administered universally to all young people.

“Now that we know that Epstein-Barr is very tightly linked to MS, we could save a lot of lives if we develop the vaccine now,” Damania said, “rather than wait 10 years” until every question is answered.

Moderna and the National Institute of Allergy and Infectious Diseases launched separate clinical trials of Epstein-Barr vaccines over the past year. Epstein-Barr vaccines also are in early stages of testing at Opko Health, a Miami-based biotech company; Seattle’s Fred Hutchinson Cancer Center; and California’s City of Hope National Medical Center.

Scientists have sought to develop vaccines against Epstein-Barr for decades only to be thwarted by the complexities of the virus. Epstein-Barr “is a master of evading the immune system,” said Dr. Jessica Durkee-Shock, a clinical immunologist and principal investigator for NIAID’s trial.

Both MS and the cancers linked to Epstein-Barr develop many years after people are infected. So a trial designed to learn whether a vaccine can prevent these diseases would take decades and a lot of money.

Moderna researchers initially are focusing on a goal more easily measured: the prevention of mononucleosis, which doubles the risk of multiple sclerosis. Mono develops only a month or so after people are infected with Epstein-Barr, so scientists won’t have to wait as long for results.

Mono can be incredibly disruptive on its own, keeping students out of class and military recruits out of training for weeks. In about 10% of cases, the crippling fatigue lasts six months or more. In 1% of cases, patients develop complications, including hepatitis and neurological problems.

For now, the clinical trials for Epstein-Barr immunizations are enrolling only adults. “In the future, the perfect vaccine would be given to a small child,” Durkee-Shock said. “And it would protect them their whole life, and prevent them from getting mono or any other complication from the Epstein-Barr virus.”

The NIAID vaccine, being tested for safety in 40 volunteers, is built around ferritin, an iron-storage protein that can be manipulated to display a key viral protein to the immune system. Like a cartoon Transformer, the ferritin nanoparticle self-assembles into what looks like a “little iron soccer ball,” Durkee-Shock said. “This approach, in which many copies of the EBV protein are displayed on a single particle, has proved successful for other vaccines, including the HPV and hepatitis B vaccine.”

Moderna’s experimental vaccine, being tested in about 270 people, works more like the company’s covid shot. Both deliver snippets of a virus’s genetic information in molecules called mRNA inside a lipid nanoparticle, or tiny bubble of fat. Moderna, which has dozens of mRNA vaccines in development, hopes to learn from each and apply those lessons to Epstein-Barr, said Sumana Chandramouli, senior director and research program leader for infectious diseases at Moderna.

“What the covid vaccine has shown us is that the mRNA technology is well tolerated, very safe, and highly efficacious,” Chandramouli said.

But mRNA vaccines have limitations.

Although they have saved millions of lives during the covid pandemic, the antibody levels generated in response to the mRNA vaccines wane after a few months. It’s possible this rapid loss of antibodies is related specifically to the coronavirus and its rapidly evolving new strains, Hotez said. But if waning immunity is inherent in the mRNA technology, that could seriously limit future vaccines.

Designing vaccines against Epstein-Barr is also more complicated than for covid. The Epstein-Barr virus and other herpesviruses are comparatively huge, four to five times as large as SARS-CoV-2, the coronavirus that causes covid. And while the coronavirus uses just one protein to infect human cells, the Epstein-Barr virus uses many, four of which are included in the Moderna vaccine.

Earlier experimental Epstein-Barr vaccines targeting one viral protein lowered the rate of infectious mononucleosis but failed to prevent viral infection. Targeting multiple viral proteins may be more effective at preventing infection, said Damania, the UNC virologist.

“If you close one door, the other door is still open,” Damania said. “You have to block infection in all cell types to have a successful vaccine that prevents future infections.”

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

Nearly Half of Adults Think U.S. Healthcare System Is Failing

By Pat Anson, PNN Editor

Almost half of American adults (44%) give the U.S. healthcare system poor or failing grades, according to a new Gallup survey that found most respondents concerned about rising medical costs and growing healthcare inequality. Overall, the healthcare system was given a barely passing grade of C-minus.

"After years of higher prices, growing inequities, skipping treatments, getting sicker, or borrowing money to pay medical bills, it's no wonder so many Americans view the health system so poorly," said Timothy Lash, President of West Health, a group of healthcare non-profits that commissioned the survey.

The survey of nearly 5,600 Americans in all 50 states was conducted in June, with a nationally representative sample reflecting racial and ethnic backgrounds.

The worst overall grade on the healthcare report card – a D-minus – was given to the cost of care. One in four adults (26%) did not seek treatment due to cost in the last three months; while one in three (35%) are concerned they will be unable to afford healthcare in the next 12 months.  

Healthcare in America Report Card

source: west health-Gallup

The affordability issue is worse for those living with chronic health conditions. About 1 in 5 skipped care to pay for other household expenses, compared to about one in eight of those without chronic conditions.

“When members of my family have needed surgeries or medications [they] have to really consider how much medical debt they’re willing to go into. Our healthcare system forces us to try and make calculations between financial security and health just because of how expensive things are, and that’s even with health insurance, so I can’t imagine if you didn’t have health insurance how fraught that would be,” said survey participant Stef Schloo, 28, who lives in Pennsylvania

“I am single and so all of that falls down on me. And the only thing that would concern me is if I really developed a major health situation or, God forbid, if I was in a major accident or had to have long-term care, that’s a great concern to me,” said Patricia Slough, 67, who lives in Massachusetts.

Quality of care was the only aspect of the healthcare system that received more positive than negative marks, although it was still only able to earn an overall grade of C-plus. Women were less likely to give good grades for quality than men (38% vs. 57%); and Black and Hispanic Americans were also less likely to give a good grade for quality than the general population (36% each vs. 47%).

“You can have some of the best doctors in the world practicing here. I’m not saying that other countries don’t have great doctors, but I think our healthcare professionals can be second to none depending on where you go in America,” said Andrew Kerner, 30, who lives in North Carolina.

Healthcare Access and Equity

The grades for access to care and equitable care also broke down along racial lines. Two-thirds of Black Americans (66%) and Asian Americans (64%) selected a grade of D or F for health equity, which is the ability of every person to get quality care regardless of race and ethnicity. By comparison, Hispanic Americans (55%) and White Americans (53%) gave a poor or failing grade to equity,

Women, Blacks, Hispanics and Asian Americans were also more critical when it came to access to care. More than 40% in each of these groups gave access D’s and F’s, compared to about a third of White Americans and men.

“For the richest country on earth I think we have the most deplorable healthcare system... due to its inequity, mainly due to the way it all depends on how much money somebody has whether they get good healthcare or not,” said Anne Courtney Davis, 71, who lives in Ohio.

The survey also found that most younger and middle-aged adults are worried that Medicare and Social Security will not be available to them when they become eligible. That sentiment cuts across political lines, with 71% of Democrats, 66% of independents and 62% of Republicans worried or extremely worried about not having access to Medicare. When it comes to Social Security, there is even more agreement — 77% of Democrats, 75% of independents and 73% of Republicans are worried it won’t be there for them when they grow older.

Under an 11-point plan by Sen. Rick Scott (R-FL), chair of the National Republican Senatorial Committee, funding for Social Security, Medicare and other so-called entitlements would have to be put to a vote in Congress every five years.

“When I witness these individuals say that Medicare should be renewed every five years, it kind of makes me nervous [it’s] not going to be there for individuals when we get older,” said Nick Lembo, 27, of Indiana. “That’s startling to me because you should want to take care of those who are older than you because eventually... you’re going to be at that age.”

New Treatment Offers Hope for Lupus Patients

By Dr. Eric Morand, Monash University, Australia

When real patients have unprecedented positive outcomes to a new treatment, it’s tempting to talk about it as “breakthrough” for medical science. This describes the excitement around a new report from researchers in Germany of a radical new treatment for lupus.

The patients in the study – five people with severe lupus – went into remission following pioneering CAR T-cell treatment, which uses genetically altered cells.

What is lupus, why is this such big news, and what could it mean for other patients and diseases?

Around 5 million people are affected by some form of lupus worldwide. The most common form of lupus is technically known as systemic lupus erythematosus. Though not widespread, it is more common than multiple sclerosis (MS). Both are “autoimmune” diseases where the immune system attacks its owner instead of the germs it is supposed to fight.

MS is an autoimmune disease where the immune system attacks nerve tissue. In contrast, lupus can affect any organ in the body. Treatments for lupus have been so poor for so long that even wealthy and famous people with the disease – like pop star and actor Selena Gomez – have had organ failure resulting in the need for a kidney transplant. A lot of complicating factors have made it hard to improve outcomes for people with the disease.

Firstly, the variety of tissues lupus can affect means no two patients are exactly alike. Diagnosis is hard and often delayed. This also means we researchers have to deal with a lot of complexity as we try to work out what is causing the disease. This clinical variability makes measuring improvement in response to treatment difficult, and many clinical trials have likely failed due to measurement issues.

Second, there is variation between patients in which part of the immune system goes wrong. This means different patients will need different treatments – and we still do not know with certainty how to get this right. But progress is happening fast.

Innate and Adaptive Immunity

The immune system is in two parts, innate and adaptive.

The “innate” immune system responds fast but non-specifically to viruses and other germs that hit the body with a slug of germ-killing inflammatory proteins. The “adaptive” immune system is slower but more precise. It swings into action after the innate immune system and provides long lasting defense against the invading germ.

When you are vaccinated against a disease (such as COVID), the fever and aches you might get in the first day or two is your innate immune system at work. But the long-lasting protection from antibodies is provided by a part of your adaptive immune system, a key part of which is delivered by cells called “B cells”.

In lupus, both parts of the immune system are involved, and both have been successfully used to develop medicines. Earlier this year, the Therapeutic Goods Administration approved anifrolumab, a drug which blocks “interferon”, a crucial protein made by the innate immune system.

Another drug which works on B cells of the adaptive immune system, called belimumab, was approved a few years ago. Unfortunately, neither drug is on Australia’s Pharmaceutical Benefits Scheme yet, so access is extremely limited.

However, we now know that interferon and B cells are both important, and so very strong treatments that almost completely eradicate either could be useful. That is where this potential new treatment comes in.

Already Used to Treat Cancer

Treatments to destroy B cells are used in cancers like lymphoma. The most powerful of these uses CAR-T cells, which train a type of natural cell to be an assassin of the B cell.

CAR-T medicines are highly complex to make, and extremely expensive – but they work.

T cells are collected from the blood, then re-engineered in a special laboratory.

Now, this new report shows targeting B cells using this approach could be effective in lupus too. Building on a first-ever patient treated in this way by the same group a year ago, doctors in Germany created a “homemade” CAR-T treatment and used it in five patients with severe lupus.

Remarkably, all five patients had near complete eradication of disease, allowing them to stop conventional medicines, like steroids, with potentially harmful side effects.

What This Means for Other Patients

So what does it mean for patients in Australia? Well, most centres aren’t able to make their own CAR-T treatments, so delivering this potential treatment will require a commercial approach.

However, it might be quicker to market than other treatments in development as it takes a proven approach into a new disease, rather than being new from the ground up.

One day we might even be able to extend such treatments to other autoimmune diseases, like MS, where B cell-directed treatments have been helpful, as well as in lupus.

This would need to be balanced against risk. Importantly, short term side effects of CAR-T treatment (which include brain and bone marrow problems) can be severe. For this reason, such a treatment would only be used for the most severe cases in which standard treatments have failed, like the patients in the German trial.

Long-term side effects are also unknown at this time, and of course suppressing the immune system so profoundly in the setting of a pandemic is not without major risks.

Formal trials of a commercial CAR-T medicine for lupus are in the advanced planning stages already, and Australia is likely to be front and centre of these due to our lupus expertise and trial-friendly regulatory environment. With all these advances, we can at last tell our patients, and our friends and family with lupus, that there is light at the end of what has been a very long tunnel.

Eric Morand, MD, is a clinical rheumatologist and Head of the School of Clinical Sciences at Monash Health, Monash University in Australia.  Dr. Morand consults with companies involved in lupus drug development, including Novartis and AstraZeneca. He receives funding from Australia’s National Health and Medical Research Council and Lupus Research Alliance US, and is a Director of Rare Voices Australia.

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

How Intractable Pain Causes Brain Tissue Loss

By Dr. Forest Tennant, PNN Columnist

The brain not only controls pain but the endocrine, cardiovascular, metabolic, respiratory and gastrointestinal systems. Any or all of these biologic systems may malfunction if there is brain tissue loss.

Beginning in 2004, brain scan studies began to document that brain tissue loss can be caused by intractable pain. Today, almost 20 years later, this important fact appears to be either unknown or a mystery to both the public and medical professionals.

Basic science researchers have unraveled the complex process of how and why this pathological phenomenon may occur. A good understanding of how this pathology develops is critical to properly care for and treat persons who develop intractable pain whether due to a disease or an injury.

What Causes Tissue Loss?

Tissue loss anywhere in the body is caused by inflammation, autoimmunity, or loss of blood supply due to trauma or disease. The brain scan studies done since 2004 that documented brain tissue loss were not done in persons who had a stroke or head trauma, but in pain patients experiencing inflammation and autoimmunity (i.e., collagen deterioration). It turns out that both biologic mechanisms may operate to cause brain tissue loss in intractable pain patients.

In the pursuit of understanding brain tissue loss and its accompanying malfunctions, it has been discovered that the brain and spinal cord (central nervous system or CNS) contain cells called microglia. They are closely akin to the immune protective cells in the blood stream which are called a “lymphocytes.”

The microglia in the CNS lay dormant until a harmful infection, toxin or bioelectric magnetic signal enters its domain, at which time it activates to capture and encapsulate the danger or produce inflammation to destroy the offender.

If the microglia are overwhelmed by some danger, such as a painful disease that isn’t cured, it produces excess inflammation that destroys some brain tissue which can be seen on special brain scans. Some viruses such as Epstein Barr may hibernate in microglia cells and create an autoimmune response, which magnifies inflammation and brain tissue loss.

Intractable pain diseases such as adhesive arachnoiditis (AA), reflex sympathetic dystrophy (CRPS/RSD), and genetic connective tissue diseases such as Ehlers-Danlos syndrome may incessantly produce toxic tissue particles and/or bioelectromagnetic signals that perpetuate microglial inflammation, tissue loss and CNS malfunctions.

This is the reason why proper pain management must have two targets: the pain generator and CNS inflammation.

How To Know You Have Lost Brain Tissue

If your pain is constant and never totally goes away, it means you have lost some brain tissue and neurotransmitters that normally shut off pain. If you have episodes of sweating, heat or anxiety, you probably have inflammation that is flaring. Naturally, if you feel you have lost some reading, calculating or memory capacity, it possibly means you have lost some brain tissue. MRI’s may also show some fibrous scars.

Fortunately, studies show that if a painful disease or injury is cured or reduced, brain tissue can regenerate. While we can’t guarantee that brain tissue will be restored, we offer here our simple, immediate and first step recommendations using non-prescription measures.

First, do you know the name and characteristics of the disease or injury that is causing your pain? Are you engaging in specific treatments to reduce or even cure your disease, or are you simply taking symptomatic pain relief medications? 

Start at least two herbal-botanical agents that have some clinical indications that they reduce inflammation in the brain and spinal cord: serrapeptase-palmitoylethanolamide (PEA) and astragalus-curcumin-luteolin-nanokinase. You can take different agents on different days. 

Increase the amount of protein (meat, fish, poultry, eggs) in your diet. Consider a collagen supplement. Limit starches and sugars. 

Start taking these vitamins and minerals:

• Vitamin C - 2,000mg in the AM & PM

• Vitamin B-12, Vitamin D

• Minerals: Magnesium and selenium

We recommend vitamins daily and minerals 3 to 5 days a week. 

The above will help you stop additional tissue loss and hopefully regenerate brain tissue.  

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. This column is adapted from bulletins recently issued by the Arachnoiditis Research and Education Project and the Intractable Pain Syndrome Research and Education Project.

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