Long Covid Research Could Lead to New Treatments for Chronic Pain

By Pat Anson, PNN Editor

About a third of people infected with Covid-19 develop long-term symptoms, such as headaches, persistent muscle pain, joint pain, stomach pain, chest pain and respiratory discomfort. Three years into the pandemic, scientists are finally beginning to understand what causes long covid and how to possibly treat it.

In studies on hamsters infected with Covid-19, researchers at the Icahn School of Medicine found that the virus left behind a gene expression signature in the animals’ dorsal root ganglia – a cluster of nerves in the spinal cord that transmit pain signals from the body to the brain. The signature matched gene expression patterns seen in other forms of chronic pain.

“A significant number of people suffering from long COVID experience sensory abnormalities, including various forms of pain,” said Randal (Alex) Serafini, an MD/PhD candidate. “We used RNA sequencing to get a snapshot of the biochemical changes SARS-CoV-2 triggers in a pain-transmitting structure called dorsal root ganglia.”

Serafini presented his findings at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics in Philadelphia. 

The symptoms experienced by hamsters infected with Covid-19 closely mirrored those of people. Researchers say the hamsters showed a slight hypersensitivity to touch early after the infection, which became more severe over time.

They performed similar experiments with the Influenza A virus to determine if other RNA viruses promote a similar response. Influenza A caused an early hypersensitivity that was more severe, but began to fade after a few days. Four weeks after recovering from the flu, the hamsters had no signs of long-term hypersensitivity.

In contrast, hamsters infected with SARS-CoV-2-showed more hypersensitivity, reflecting symptoms of chronic pain. The pain sensitivity remained even after the hamsters recovered from the initial Covid-19 infection. Further research found that SARS-CoV-2 downregulates the activity of several previously identified pain regulators and a protein called interleukin enhancer binding factor 3 (ILF3) — a potent cancer regulator.

Based on these findings, the researchers hypothesized that mimicking the acute effects of ILF3 could serve as a new pain treatment strategy. To test this theory, they gave laboratory mice suffering from inflammation a clinically tested anti-cancer drug that inhibits ILF3 activity. The drug was very effective at treating their pain.

“Our findings could potentially lead to new therapies for patients suffering from acute and long COVID, as well as other pain conditions,” said Serafini. “We think therapeutic candidates derived from our gene expression data, such as ILF3 inhibitors, could potentially target pain mechanisms that are specific to COVID patients, both acutely and chronically.

“Interestingly, we saw a few cancer-associated proteins come up as predicted pain targets, which is exciting because many drugs have already been developed to act against some of these proteins and have been clinically tested. If we can repurpose these drugs, it could drastically cut down therapeutic development timeline.”

Serafini and his colleagues are now working to identify other compounds that could be repurposed to treat pain, while also keeping an eye out for new compounds that might inhibit ILF3 activity.

“Our study also shows that SARS-CoV-2 causes long-term effects on the body in drastically new ways, further underscoring why people should try to avoid being infected,” he said.

Another study has suggested that long covid appears to be the result of an overactive immune system. Australian researchers identified biomarkers of a sustained inflammatory response in the blood samples of long covid patients – suggesting their immune systems were activated by the virus, but then failed to turn off.

Other studies have found similarities between long covid and autoimmune conditions such as lupus and myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS).  

In addition to widespread body pain, long covid symptoms include fatigue, cognitive impairment and difficulty sleeping.    

Better Pain Treatment Needed for People with Severe Mental Illness

By Pat Anson, PNN Editor

There is an urgent need to improve the way pain is diagnosed and treated in people with severe mental illness, according to a new review by UK researchers.

Depression and pain commonly co-exist, with pain prevalence in people with depression estimated at 65 percent. Pain is also experienced by 29% of people with bipolar disorder, about double that of healthy people.

But while the association between pain and mental illness is well-established, researchers say pain is not routinely assessed and managed in people with SMI, due in part to discrimination by healthcare providers. Mental health problems carry a fair amount of stigma – just like pain itself -- which impedes treatment.

“Healthcare professionals underestimate pain in the presence of perceived ‘psychosocial’ problems, making discounting of pain in people with SMI particularly likely. Indeed, there is evidence that they experience diagnostic overshadowing for physical healthcare,” lead author Whitney Scott, PhD, Kings College London, reported in PAIN, the official journal of the International Association for the Study of Pain (IASP).

“In addition to limiting treatment access, pain-related invalidation, stigma, and discrimination exacerbate distress. Investigation is needed to understand the impact of intersecting experiences of stigma and discrimination in people with SMI and pain, and how to address these.”

Scott and her colleagues say there is limited knowledge about the effectiveness of pain treatments in people with SMI because they are often excluded from clinical trials due to their perceived “complex mental health needs.”

Even when pain is diagnosed, providers may be reluctant to prescribe analgesics to people with SMI because it may interact with mental health drugs they are already taking.

“Pharmacological management of pain in SMI is complicated by the potential for harmful side effects and interactions with psychotropic medications and the underlying mental health condition,” said Scott. “Antidepressants, including serotonin-noradrenaline reuptake inhibitors, are effective for pain management in the absence of depression and of course may improve co-morbid depression; however, unopposed anti-depressants may destabilise mood in bipolar disorder. Collaborative pharmacological and psychological care for comorbid pain and major depression is promising, but scarce.”

Little is also known about the effectiveness of non-pharmacological pain treatments, such as exercise and physical therapy, because people with SMI often experience isolation, fatigue and mood disorders, making them harder to motivate.  

To overcome these barriers, Scott and her co-authors say pain and mental healthcare need to be more fully integrated, with caregivers, mental health professionals, pain specialists and policymakers working together to enable more personalized care and understanding of the needs of people with SMI.

$23 Billion Raised for Rare Disease Drug Development

By Roger Chriss, PNN Columnist

Monday, February 28 is Rare Disease Day, a global effort to recognize and raise awareness of rare diseases. The annual event has been held every year since 2008, but has taken on a new tenor amid Covid-19. Long Covid has become one of the biggest threats the coronavirus poses. But like rare diseases, long Covid is not often discussed in public health messaging about the pandemic.

The National Organization of Rare Disorders officially recognizes over 7,000 rare diseases. But the actual number is much higher. Each year some 250 new rare diseases are identified, and existing rare diseases like Charcot-Marie-Tooth disease and Ehlers-Danlos syndromes have new types and subtypes identified.

Rare diseases are often only familiar to the people who live with them and the specialists who treat them. For the goal of treatment to be met, rare diseases must be named and characterized. In Europe, a disease is classified as rare if it affects fewer than 1 in 2,000 people, while in the U.S. rare diseases are recognized as conditions that affect fewer than 200,000 people nationally.

They may be rare, but their impact is substantial. A recent study in the Orphanet Journal of Rare Diseases estimates that rare diseases affect 25 to 30 million people in the U.S. and more than 300 million people worldwide. Patients and their families have to endure a lengthy “diagnostic odyssey,” often at high financial and emotional cost.

The graphic below helps demonstrate the many barriers that a rare disease patient may encounter in getting a proper diagnosis, such as lack of knowledge about a disease, an overlap of symptoms, lack of diagnostic tests, and inaccurate test results.

According to the U.S. Government Accountability Office, the total cost of rare diseases in 2019 reached $966 billion, counting both direct medical costs and other indirect expenses such as loss of income. But research funding for rare disease has long been limited, in part because of the difficulty in diagnosing them.

Fortunately, that may be changing. A new report by the non-profit Global Genes estimates that nearly $23 billion was raised in 2021 from public and private sources to fund rare disease drug development. That’s a 28 percent increase over the money raised in 2020.

“Rare diseases continue to have a strong allure to investors, as evidenced by the significant capital raised in 2021 to advance companies and pipelines focused on rare conditions,” said Craig Martin, CEO of Global Genes. “We hope and expect that the sector will continue to be strengthened by the vast array of opportunities to advance promising biotechnologies, under expedited review, that can address the tremendous burdens and underlying causes of thousands of rare, genetic conditions currently without approved treatments.”

The past year saw many positive steps toward improving the diagnosis and treatment of rare diseases. Congress is considering the Speeding Therapy Access Today (STAT) Act of 2021,  which requires policy reforms at the FDA to speed up the development of treatments for rare diseases.

Although the STAT Act has yet to pass, the FDA has already taken action to address two rare diseases. The agency recently approved Pyrukynd (mitapivat) tablets to treat hemolytic anemia in adults with pyruvate kinase deficiency and Vyvgart (efgartigimod) for the treatment of generalized myasthenia gravis.

The past year also saw efforts to improve research and data collection for rare diseases. AllStripes added 100 rare disease research programs to its efforts, and RARE-X launched its initial set of data collection programs. And Rare Diseases International started its Collaborative Global Network for Rare Diseases to create a “a person-centered network of care and expertise” for people living with rare diseases.

But more work needs to be done. The EveryLife Foundation for Rare Diseases notes that 93% of rare diseases have no FDA-approved treatment. In some cases, the pathophysiology is not well understood and animal models do not even exist. In other cases, although the disease is known and treatments do exist, there are too few clinicians and too little financial support for patients.

For people with rare diseases, every day is “rare disease day.” Hopefully efforts to recognize and increase awareness of rare diseases will promote more progress in their diagnosis and treatment.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research. 

Study Finds Low Risk of Muscle Pain From Statins

By Pat Anson, PNN Editor

Have you experienced muscle pain, memory loss or other side effects from statins? If so, you’re not alone. A many as one in two patients stop taking the cholesterol-lowering drugs because they don’t like the side-effects.

But the authors of a large new study say statin intolerance is over-estimated and over-diagnosed, resulting in too many patients raising their risk of heart disease because they refuse to take the drugs.

An international team of researchers conducted a meta-analysis of 176 clinical studies involving over 4 million statin users and found that only about 9 percent have statin intolerance. Their findings are published in the journal European Heart Journal.

“I believe the size of our study, which is the largest in the world to investigate this question, means we are able to finally and effectively answer the question about the true prevalence of statin intolerance,” said lead author Maciej Banach, MD, a cardiologist and professor at Medical University of Lodz and the University of Zielona Góra in Poland.

“Patients need to know that statins may prolong their life, and in cases where side effects appear, we have enough knowledge to manage these effectively. The most important message to patients as a result of this study is that they should keep on taking statins according to the prescribed dose, and discuss any side effects with their doctor, rather than discontinuing the medication.”

The research team found that patients who are older, female, obese, diabetic, or suffering from an under-active thyroid or chronic liver or kidney failure were more likely to be statin intolerant.

Patients taking drugs used to control an irregular heartbeat or calcium channel blockers for chest pain and high blood pressure were also more likely to have side effects, as did those with high alcohol consumption.

“It is critically important to know about these risk factors so that we can predict effectively that a particular patient is at higher risk of statin intolerance. Then we can consider upfront other ways to treat them in order to reduce the risk and improve adherence to treatment. This could include lower statin doses, combination therapy and use of innovative new drugs,” said Banach. 

“Most cases of statin intolerance observed in clinical practice are associated with effects caused by patients’ misconceptions about the side effects of statins or may be due to other reasons. Therefore, we should carefully evaluate symptoms, assessing in detail patients’ medical histories, when the symptoms appeared, specific details of pain, other medications the patients are taking, and other conditions and risk factors. Then we will see that statins can be used safely in most patients.”

Previous research on side effects from statins have had mixed results. A 2017 study found that only about 2 percent of patients on Lipitor (atorvastatin) had muscle pain. That finding is in marked contrast to a Cleveland Clinic study, which found that 42% of patients taking Lipitor reported muscle pain and weakness.

In 2014, the Food and Drug Administration required warning labels on statins, cautioning that statins can cause a muscle injury called myopathy, which is characterized by muscle pain or weakness. In rare instances, the FDA says statins can also cause liver injury, diabetes and memory loss.

U.S. Ranked Poorly in End-of-Life Care

By Pat Anson, PNN Editor

The U.S. healthcare system barely gets a passing grade in caring for dying patients, ranking well behind most developed countries and even some third world nations, according to a new analysis of end-of-life care around the world.

The United Kingdom earned the highest ranking in the study, followed by Ireland, Taiwan, Australia, South Korea and Costa Rica, which all earned A grades. The U.S. earned a C grade, ranking 43rd of the 81 countries evaluated. Nigeria, Guatemala, Botswana, Romania, Mongolia and several other low-income countries had higher grades than the U.S.  

“Many individuals in both the developed and developing world die very badly – not at their place of choice, without dignity, or compassion, with a limited understanding about their illness, after spending down much of their savings, and often with regret about their course of treatment. These things are very common,” lead author Eric Finkelstein, PhD, a palliative care expert and professor at Duke University’s Global Health Institute, said in a news release.

Top 10 Countries on Quality of Death Index

SOURCE: LIEN FOUNDATION

The study findings, recently published in the Journal of Pain and Symptom Management, are based on a survey of 181 palliative care experts around the world who were asked how well their own countries provided for the physical and emotional wellbeing of dying patients.

Over a dozen health factors were evaluated, including pain management, being treated kindly, affordability, spiritual and emotional needs, and providing patients with a clean and safe space. Treatments that address quality of life, rather than just extending life, were also an important consideration.          

“Perhaps the main conclusion from this important exercise is that most people in the world die badly -- many through no treatment at all and many through excessive often futile treatment that increases suffering,” says Richard Smith, a palliative care expert and former editor of the British Medical Journal.

It’s no surprise that most developed countries with well-funded healthcare systems rated highly in end-of-life care, while poorer countries fared worse.

“The overwhelming need for palliative care is in low and middle-income countries, where less than a third of services exist,” said co-author Stephen Connor, executive director of the Worldwide Hospice Palliative Care Alliance.

The obvious exception to that is the United States’ lackluster rating. Researchers say that’s because healthcare decisions in the U.S. are often based on last-ditch efforts to extend life, rather than ensuring comfort and quality of life in a patient’s final days.  

“We spend so much money trying to get people to live longer, but we don’t spend enough money in helping people die better,” says Finkelstein, who is also the director of the Lien Centre for Palliative Care at Duke-NUS.

The study was funded by the Lien Foundation, a Singapore-based nonprofit focused on improving quality of life. Previous surveys of palliative care experts by the foundation ranked the U.S. 9th on the “Quality of Death” index in 2010 and in 2015.

Finkelstein says the covid pandemic has opened a window into end-of-life care, with millions of patients spending their dying moments alone, often separated from their families and without emotional support.

“Generally, people don’t talk about death. COVID has made it less taboo. We have an opportunity to continue this discussion and not just help COVID patients, but to help everyone have a better end-of-life experience,” he said.

Finkelstein hopes the study will spur action from policymakers to improve conditions for dying patients, such as loosening restrictions on pain medication. A recent study in Oregon found that overzealous enforcement of opioid guidelines led to a significant decrease in opioid prescribing to patients being admitted to hospice, resulting in some terminally ill patients suffering needlessly.

Finkelstein urges people to ensure a better end-of-life experience for themselves and their loved ones by making an end-of-life plan and discussing it with family and friends.

“Do an advanced care plan or at least express your wishes to friends and family,” Finkelstein says. “Don’t wait. By the time you fall ill, it may be too late and folks may not know what you want.”

Microplastic Particles Linked to IBD

By Pat Anson, PNN Editor

Microplastics — tiny bits of plastic so small they are invisible to the naked eye --- can be found in our food, water and even the air we breathe. But research is only beginning on the prevalence and health effects of plastic particles in humans.

A 2020 study found that babies fed formula from plastic bottles swallowed millions of microplastic particles every day. And a recent review that looked at the impact of microplastics on human cells found evidence of cell death, immune response and damage to cell walls.

“We are exposed to these particles every day: we’re eating them, we’re inhaling them. And we don’t really know how they react with our bodies once they are in,” lead author Evangelos Danopoulos, a postgraduate student at Hull York Medical School in the UK told The Guardian.

For the first time, Chinese researchers have now found evidence that people with inflammatory bowel disease (IBD) have more microplastics in their feces, suggesting that plastic particles in the digestive tract could play a role in the development of Crohn’s disease and ulcerative colitis.

Researchers obtained fecal samples from 52 people with IBD and 50 healthy people from different geographic regions of China. They found that feces from the IBD patients had significantly more microplastics than the control group – an average of 41.8 particles per gram in the IBD group vs. 28 particles in healthy people. People with more severe IBD symptoms had higher levels of microplastics. Their particles also tended to be smaller.

ENVIRONMENTAL SCIENCE AND TECHNOLOGY

Researchers surveyed both groups and found that people who consumed more bottled water and takeaway food, and were often exposed to dust had more microplastics (MPs) in their feces. The two most common types of plastic found were polyethylene terephthalate (PET; used in bottles and food containers) and polyamide (PA; found in food packaging and textiles).

Still unclear is whether exposure to microplastics causes or contributes to IBD, or whether people with IBD simply accumulate more microplastics in their digestive tracts because of their disease.

“We conclude that the plastic packaging of drinking water and food and dust exposure are important sources of human exposure to MPs. Furthermore, the positive correlation between fecal MPs and IBD status suggests that MP exposure may be related to the disease process or that IBD exacerbates the retention of MPs,” researchers reported in the journal Environmental Science & Technology.

The prevalence of IBD is rising around the world. A 2015 CDC study estimated that about 3.1 million adults in the U.S. were diagnosed with IBD, nearly double the 1.8 million Americans who reported having IBD in 1999. The researchers found an association between IBD and people with lower income and education levels, but did not look into the role of microplastics.

Rare Disease Spotlight: Valley Fever

By Barby Ingle, PNN Columnist 

As the final article in my series on rare diseases, I am going to cover something that has been impacting my life for the past 2 years and 25 days – coccidioidomycosis --- otherwise known as Valley fever. This is a health challenge that has been difficult and longer lasting than typical for a patient like me. I have headaches, chest pain and feel exhausted.

Tests show that I am still positive for Valley fever, both the active fungal infection and the antibodies my body produces to fight it. Over the past few weeks, I feel more pressure in my lungs, as if Valley fever pneumonia is returning. I am more exhausted than ever and have skin blisters again. I liken them to shingles, as I have had them multiple times over the past few years and it usually happens during periods of stress.

I took an antiviral, but maybe it is the Valley fever that is showing itself again as my breathing decreases. I can tell this by feel, as well as testing my blood oxygen levels and heart rate hourly over the past week. My coughing and shortness of breath have also increased.

Is this a new exposure or just the same old, same old? I have a close family member going through Covid currently and have been extremely careful not to get it, but I wonder. I have been tested for Covid 5 times now over the past 2 weeks with 3 home tests, a rapid test and a PCR test. All of these were negative, for which I thank God. But the symptoms of Covid and Valley fever seem to be similar.  

BARBY INGLE

When I first got the Valley fever in 2019, PNN did an article about what I was going through and the growing number of cases in the Southwest. Little did I know I would still be dealing with Valley fever more than 2 years later.

My lung specialist told me it would take about one year to get over it. The variable we did not know at that time was that I was allergic to the one medication that is invented specifically for coccidioidomycosis.

Since my diagnosis, I have been extremely tired -- more than I was with any of the other chronic and rare diseases I live with. I do not know if this is a new infection or if my immune system is compromised by all that I live with. I do know I am tired. All of the time.

It has also put my thinking and ability to handle pain into a new view. I am now very mindful of my breathing, getting oxygen appropriately, and any tingling sensations. That is the feeling I get when my oxygen levels are low. I used to worry more about the burning fire pain from RSD. That is still there and is constant, too. However, if I can’t breathe, the pain doesn’t matter as I won’t be able to live. 

How does one get coccidioidomycosis? The coccidioides fungus that causes it is found in soil of the desert Southwest and causes infection when inhaled. You can get it simply by breathing in microscopic fungus spores. Even our pets, especially dogs, can get Valley fever. It is not passed from human to human, although if you breathe the same air, you may see a cluster of people with it.

My husband Ken was tested for Valley fever after I developed it. His lungs show that he did have it, though he has a great immune system and showed no signs or symptoms. His body just beat it.

For people like me with suppressed immune systems, the risk is high for complications and severe symptoms if we become infected. I was actually misdiagnosed at first because Valley fever does resemble a flu with fever, cough, chills and chest pain. Once it turned into pneumonia and I was treated for a bacterial infection, it was figured out.

Ironically, my lung specialist thought that Ken and I probably got it from driving with the car windows down for fresh air. Valley fever cases spike when summer monsoons hit and cause dirt devils, and after earthquakes when fungal spores are kicked up into the atmosphere.

Worldwide and nationally, Valley fever is considered a rare condition. But in the U.S. Southwest and northern Mexico it is more common. If you are visiting the Southwest or live here, it is a condition you should know about and understand. The sooner you can take action against it or not be exposed to it, the better. Arizona, where I live, accounts for about two-thirds of the cases each year.   

Most infections last for a few weeks or months, but some patients like me can have symptoms that last longer. Because I experienced such a severe case at the start, I have long-term damage in my lungs and will likely continue to have challenges with my breathing and energy.  

I hope that you have enjoyed my series on rare diseases and have found the information educational, useful and motivating. I would love if more people understood the 7,000 plus rare diseases just a little better. I still have a long way to go to understand and learn about them. I have only scratched the surface. It has given me a better understanding of the diversity in conditions, the similarities that patients with rare diseases experience, and an empathy for those fellow patients who I advocate for as often as I can.

Barby Ingle lives with reflex sympathetic dystrophy (RSD), migralepsy and endometriosis. Barby is a chronic pain educator, patient advocate, and president of the International Pain Foundation. She is also a motivational speaker and best-selling author on pain topics. More information about Barby can be found at her website.

Guidelines Urge More Caution in Use of Invasive Neck Procedures

By Pat Anson, PNN Editor

Invasive procedures such as steroid injections, nerve blocks and radiofrequency ablation should be used more cautiously when treating chronic neck pain, according to new guidelines adopted by the American Academy of Pain Medicine and American Society of Regional Anesthesia and Pain Medicine.

The two medical societies formed a joint guidelines committee in 2020 to look into cervical spine joint procedures, which are increasingly used despite questions about their effectiveness and safety. The use of radiofrequency ablation -- heat from an electric current used to burn painful nerve endings — has increased by 112% in the U.S. over the past decade.

Spine pain in the neck or lower back is the leading cause of disability worldwide, with nearly half of adults likely to be affected at some point in their lives. The cervical facet joints, which allow the neck and back to tilt forwards, backwards and to rotate, are the primary source of pain in about 40% of patients with chronic neck pain and over half of those with neck pain after whiplash injury.

"It is precisely because neck pain and cervical spine procedures are so common, and there is so little high-quality evidence to guide care, that consensus guidelines are needed,” says lead author Steven Cohen, MD, a professor of anesthesiology at Johns Hopkins Hospital and co-chair of the guidelines committee.

The new guidelines, published online in the journal Regional Anesthesia & Pain Medicine, are based on over 400 publications and clinical studies of cervical spine procedures. Reviewers also looked at clinical signs and imaging used to select patients for particular procedures; the diagnostic and prognostic value of procedures; and several aspects of radiofrequency ablation (RFA), including how to reduce the risk of complications from the procedure and whether it should be repeated.

Because acute neck pain often resolves by itself, the guidelines recommend 6 weeks of conservative management, such as non-opioid painkillers and physical therapy, before opting for RFA or nerve blocks.

The reviewers found that RFA may be helpful for easing chronic neck pain, but only in patients whose pain corresponds to the joints being treated; those whose symptoms don’t emanate from a nerve root; and those who obtain meaningful pain relief from diagnostic nerve blocks, which are typically performed before RFA. 

Many insurance carriers require two nerve blocks, but the evidence indicates that doubling up will result in a significant number of unnecessary procedures and higher costs. Reviewers say the evidence for performing only a single block is much stronger for the neck than for the lower back.

The guidelines also recommend against stringent patient selection criteria, such as requiring nearly total pain relief from diagnostic blocks, because it might exclude patients who might benefit from radiofrequency ablation. None of the clinical studies that were reviewed support using pain relief thresholds above 50 percent.

Physicians should warn patients about the common side effects of RFA, such as tingling and burning sensations, numbness, dizziness, and loss of balance and coordination, which can last from a few days to a few weeks after the procedure. Patients also need to be told that RFA won’t cure them, and that pain relief typically lasts between 6 and 14 months. 

While most patients who have the procedure repeated will get pain relief, the benefits may wane over several years. RFA shouldn’t be repeated more than twice a year, the guidelines recommend.

Other key recommendations include:

• Use only soluble, short-acting steroids when injecting into the upper neck joints

• Use fluoroscopy imaging before spinal injections to avoid inadvertent needle placement

• Use smaller needles and electrodes than those used for the lower back

• Use nerve and muscle stimulation to improve effectiveness and reduce the risk of complications

• Take steps to minimize interference with implanted electrical devices such as pacemakers

“Clinical trials evaluating cervical facet blocks and RFA are characterized by widely disparate outcomes, and there is enormous variation in selecting patients and performing procedures. These multi-society guidelines have been developed to serve as a roadmap to improve outcomes, enhance safety, and minimize unnecessary tests and procedures,” the reviewers concluded.

Integrative and Comprehensive Pain Management Provide Only Small Benefits

By Pat Anson, PNN Editor

As concerns rose in recent years about opioid addiction and overdoses, it became trendy for healthcare providers to offer “comprehensive” or “integrative” pain management programs to patients – usually a combination of medication, physical and behavioral therapy, lifestyle changes and alternative treatments such as massage and acupuncture.

But a new study commissioned by the Agency for Healthcare Research and Quality (AHRQ) found that integrative and comprehensive pain management provide only small improvements in pain and function for people with chronic pain.   

Researchers at Oregon Health & Science University (OHSU) reviewed 57 “fair quality” clinical studies, most involving patients with moderate chronic pain caused by fibromyalgia, osteoarthritis and musculoskeletal conditions. Although the improvements in pain and function were small and the evidence limited, researchers concluded that integrative (IPMP) and comprehensive (CPMP) pain management programs worked about as well as individual treatments.

“Our review suggested that IPMPs and CPMPs may provide small to moderate improvements in function and small improvements in pain for patients with chronic pain compared with usual care and may be more effective than some medications alone. The average improvements in function and pain in our review were consistent with those reported for other therapies for pain, including opioids for chronic pain, nonpharmacologic treatments, and surgery,” researchers found.

One of the problems researchers encountered was the mish-mash of terms used to define integrative and comprehensive pain management – such as multimodal, multidisciplinary, interdisciplinary and biopsychosocial – the meaning of which often varies from provider to provider. Researchers said there was “no firm consensus on their definition or use,” which made it harder to evaluate their effectiveness. Only a few of the reviewed studies compared treatments head-to-head and many were of poor quality.

Although none of the trials specifically included Medicare patients, researchers concluded that IPMPs and CPMPs should be more widely used to address pain in the Medicare population.   

“To the extent that programs are tailored to patients’ needs, our findings are potentially applicable to the Medicare population. Programs that address a range of biopsychosocial aspects of pain, tailor components to patient need, and coordinate care may be of particular importance in this population,” they said. 

“Although use of selected individual treatments may serve some patients, a broader range of therapies that address the full scope of biopsychosocial concerns available in formal programs may benefit others. Research in the Medicare population and in patients with a broader range of pain conditions is needed as is research on the impact of program structures, coordination methods, and components on patient outcomes. Additional evidence from primary care-based programs is particularly needed.” 

One of the co-authors of the AHRQ study is Dr. Roger Chou, a primary care physician who heads the Pacific Northwest Evidence-based Practice Center at OHSU.  Chou, who co-authored the 2016 CDC opioid guideline, is a prolific researcher who has collaborated on several occasions with members of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid advocacy group.

PROP Vice President Gary Franklin, MD, “provided input” on the AHRQ study, as well as others.

In July, Chou declared a conflict of interest and recused himself from a meeting of the CDC’s Board of Scientific Counselors, which is evaluating a revision and possible expansion of the agency’s controversial guideline. Chou’s recusal apparently applied only to that meeting, as he is one of the co-authors of the revised opioid guideline — which has yet to be released publicly — and continues his involvement in federally funded pain research. 

OHSU researchers have conducted a series of reviews on a wide variety of pain therapies for the AHRQ. According to the website GovTribe, over the last five years OHSU has been awarded over $2 billion in federal grants for medical research. 

A group of patient advocates and researchers recently called for a congressional or DOJ investigation of the CDC opioid guideline, due to Chou’s significant role in writing it and his then-undeclared conflicts of interest.

Ageism in Healthcare: ‘They Treat Me Like I’m Old and Stupid’

By Judith Graham, Kaiser Health News

Joanne Whitney, 84, a retired associate clinical professor of pharmacy at the University of California-San Francisco, often feels devalued when interacting with health care providers.

There was the time several years ago when she told an emergency room doctor that the antibiotic he wanted to prescribe wouldn’t counteract the kind of urinary tract infection she had. He wouldn’t listen, even when she mentioned her professional credentials. She asked to see someone else, to no avail.

“I was ignored and finally I gave up,” said Whitney, who has survived lung cancer and cancer of the urethra and depends on a special catheter to drain urine from her bladder. An outpatient renal service later changed the prescription.

Then, earlier this year, Whitney landed in the same emergency room, screaming in pain, with another urinary tract infection and a severe anal fissure. When she asked for Dilaudid, a powerful narcotic that had helped her before, a young physician told her, “We don’t give out opioids to people who seek them. Let’s just see what Tylenol does.”

Whitney said her pain continued unabated for eight hours.

“I think the fact I was a woman of 84, alone, was important,” she told me. “When older people come in like that, they don’t get the same level of commitment to do something to rectify the situation. It’s like ‘Oh, here’s an old person with pain. Well, that happens a lot to older people.’”

Whitney’s experiences speak to ageism in health care settings, a long-standing problem that’s getting new attention during the covid pandemic, which has killed more than half a million Americans age 65 and older.

Ageism occurs when people face stereotypes, prejudice or discrimination because of their age. The assumption that all older people are frail and helpless is a common, incorrect stereotype. Prejudice can consist of feelings such as “older people are unpleasant and difficult to deal with.” Discrimination is evident when older adults’ needs aren’t recognized and respected or when they’re treated less favorably than younger people.

In health care settings, ageism can be explicit. An example: plans for rationing medical care (“crisis standards of care”) that specify treating younger adults before older adults. Embedded in these standards, now being implemented by hospitals in Idaho and parts of Alaska and Montana, is a value judgment: Young peoples’ lives are worth more because they presumably have more years left to live.

Justice in Aging, a legal advocacy group, filed a civil rights complaint with the U.S. Department of Health and Human Services in September, charging that Idaho’s crisis standards of care are ageist and asking for an investigation.

‘They Don’t Respect You’

In other instances, ageism is implicit. Dr. Julie Silverstein, president of the Atlantic division of Oak Street Health, which operates more than 100 primary care centers for low-income seniors in 18 states, gives an example of ageism: doctors assuming older patients who talk slowly are cognitively compromised and unable to relate their medical concerns. If that happens, a physician may fail to involve a patient in medical decision-making, potentially compromising care, Silverstein said.

Emogene Stamper, 91, of the Bronx in New York City, was sent to an under-resourced nursing home after becoming ill with covid in March. “It was like a dungeon,” she remembered, “and they didn’t lift a finger to do a thing for me.” The assumption that older people aren’t resilient and can’t recover from illness is implicitly ageist.

Stamper’s son fought to have his mother admitted to an inpatient rehabilitation hospital where she could receive intensive therapy. “When I got there, the doctor said to my son, ‘Oh, your mother is 90,’ like he was kind of surprised, and my son said, “You don’t know my mother. You don’t know this 90-year-old,” Stamper told me. “That lets you know how disposable they feel you are once you become a certain age.”

At the end of the summer, when Stamper was hospitalized for an abdominal problem, a nurse and nursing assistant came to her room with papers for her to sign. “Oh, you can write!” Stamper said the nurse exclaimed loudly when she penned her signature. “They were so shocked that I was alert, it was insulting. They don’t respect you.”

Nearly 20% of Americans age 50 and older say they have experienced discrimination in health care settings, which can result in inappropriate or inadequate care, according to a 2015 report. One study estimates that the annual health cost of ageism in America, including over- and undertreatment of common medical conditions, totals $63 billion.

Nubia Escobar, 75, who emigrated from Colombia nearly 50 years ago, wishes doctors would spend more time listening to older patients’ concerns. This became an urgent issue two years ago when her longtime cardiologist in New York City retired to Florida and a new physician had trouble controlling her hypertension.

Alarmed that she might faint or fall because her blood pressure was so low, Escobar sought a second opinion. That cardiologist “rushed me — he didn’t ask many questions and he didn’t listen. He was sitting there talking to and looking at my daughter,” she said.

It was Veronica Escobar, an elder law attorney, who accompanied her mother to that appointment. She remembers the doctor being abrupt and constantly interrupting her mother. “I didn’t like how he treated her, and I could see the anger on my mother’s face,” she told me. Nubia Escobar has since seen a geriatrician who concluded she was overmedicated.

The geriatrician “was patient,” Nubia Escobar told me. “How can I put it? She gave me the feeling she was thinking all the time what could be better for me.”

Pat Bailey, 63, gets little of that kind of consideration in the Los Angeles County, California, nursing home where she’s lived for five years since having a massive stroke and several subsequent heart attacks.

“When I ask questions, they treat me like I’m old and stupid and they don’t answer,” she told me in a telephone conversation

“When I tell them what hurts, they just ignore it or tell me it’s not time for a pain pill.”

— Nursing home resident

One nursing home resident in every five has persistent pain, studies have found, and a significant number don’t get adequate treatment. Bailey, whose left side is paralyzed, said she’s among them. “When I tell them what hurts, they just ignore it or tell me it’s not time for a pain pill,” she complained.

Most of the time, Bailey feels like “I’m invisible” and like she’s seen as “a slug in a bed, not a real person.” Only one nurse regularly talks to her and makes her feel she cares about Bailey’s well-being.

“Just because I’m not walking and doing anything for myself doesn’t mean I’m not alive. I’m dying inside, but I’m still alive,” she told me.

Ed Palent, 88, and his wife, Sandy, 89, of Denver, similarly felt discouraged when they saw a new doctor after their long-standing physician retired. “They went for an annual checkup and all this doctor wanted them to do was ask about how they wanted to die and get them to sign all kinds of forms,” said their daughter Shelli Bischoff, who discussed her parents’ experiences with their permission.

“They were very upset and told him, ‘We don’t want to talk about this,’ but he wouldn’t let up. They wanted a doctor who would help them live, not figure out how they’re going to die.”

The Palents didn’t return and instead joined another medical practice, where a young doctor barely looked at them after conducting cursory examinations, they said. That physician failed to identify a dangerous staphylococcus bacterial infection on Ed’s arm, which was later diagnosed by a dermatologist. Again, the couple felt overlooked, and they left.

Now they’re with a concierge physician’s practice that has made a sustained effort to get to know them. “It’s the opposite of ageism: It’s ‘We care about you and our job is to help you be as healthy as possible for as long as possible,’” Bischoff said. “It’s a shame this is so hard to find.”

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

Can Psychotherapy Treat Chronic Back Pain?

By Pat Anson, PNN Editor

Anyone who has lived with chronic back pain knows how difficult it is to treat. Pain medications provide only temporary relief, and surgeries and injections can be risky.

An extensive review of back pain treatments by The Lancet concluded that many were of “dubious benefit” and that most people with low back pain would respond to “simple physical and psychological therapies” that keep them active.

A small study recently published in JAMA Psychiatry lends some support to that belief, finding that two-thirds of chronic back pain patients who received a novel psychological treatment called Pain Reprocessing Therapy (PRT) were pain-free or nearly pain-free after four weeks. Most continued to experience relief for a year.

The researchers behind the study liken chronic pain to an alarm clock stuck in the “on” position long after the initial injury has healed.

“For a long time we have thought that chronic pain is due primarily to problems in the body, and most treatments to date have targeted that,” said lead author Yoni Ashar, PhD, a postdoctoral associate at Weill Cornell Medical College. “This treatment is based on the premise that the brain can generate pain in the absence of injury or after an injury has healed, and that people can unlearn that pain. Our study shows it works.”

PRT therapy was developed by Alan Gordon, a Los Angeles-based psychotherapist and author of a new book on healing chronic pain called “The Way Out.”

PRT is based on the premise that patients can reduce or even eliminate chronic pain by changing the way they think about it, using mindfulness and cognitive behavioral therapy. The goal is to eliminate fear and avoidance techniques that many patients have about their pain.

“The idea is that by thinking about the pain as safe rather than threatening, patients can alter the brain networks reinforcing the pain, and neutralize it,” Ashar explained.

For the randomized controlled trial, Ashar and his colleagues recruited 151 people who had low to moderate back pain for at least six months, with an intensity of at least four on a pain scale of zero to 10.

Those in the treatment group received 8 one-hour sessions of PRT, in which they were encouraged to reappraise the severity of their pain by engaging in movements they were afraid to do. This helped them overcome some of the negative emotions they had about pain. 

After four weeks, 66 percent of patients in the treatment group were pain-free or nearly pain-free, compared to 20% in a placebo group and 10% who received no treatment.

The findings were confirmed post-treatment by MRI brain scans, which showed that brain regions associated with pain processing – such as the anterior insula and anterior midcingulate — had quieted significantly in those who had PRT therapy. 

“The magnitude and durability of pain reductions we saw are very rarely observed in chronic pain treatment trials,” Ashar said.

The study focused only on PRT therapy for back pain, so future studies are needed to determine if PRT would produce similar results for other types of chronic pain. 

“This study suggests a fundamentally new way to think about both the causes of chronic back pain for many people and the tools that are available to treat that pain,” said co-author Sona Dimidjian, PhD, a professor of psychology and neuroscience at CU Boulder. “It provides a potentially powerful option for people who want to live free or nearly free of pain.”

Surprise Discovery Could Lead to Vaccine for Rheumatoid Arthritis

By Pat Anson, Editor

A surprise discovery at a university laboratory could lead to a vaccine that can prevent rheumatoid arthritis, a chronic and incurable disease in which the body’s own immune system attacks joint tissues.

Researchers at The University of Toledo years were studying a protein called 14-3-3 zeta and its role in immune system pathologies. Previous studies have suggested the protein could be a possible trigger for rheumatoid arthritis (RA) and other autoimmune conditions that cause pain, inflammation and bone erosion.

But researchers found just the opposite. The team discovered that 14-3-3 zeta proteins may actually help prevent arthritis. When they removed the proteins through gene-editing technology, it caused severe early onset arthritis in laboratory animals.

Realizing that the proteins may be beneficial, the team developed an experimental vaccine using purified 14-3-3 zeta protein grown in a bacterial cell. They found the vaccine promoted a strong, immediate and long-lasting response in rodents that protected them from RA.

"Much to our happy surprise, the rheumatoid arthritis totally disappeared in animals that received a vaccine," said Ritu Chakravarti, PhD, an assistant professor at UToledo College of Medicine and lead author of research published in the journal Proceedings of the National Academy of Sciences. "Sometimes there is no better way than serendipity. We happened to hit a wrong result, but it turned out to be the best result. Those kinds of scientific discoveries are very important in this field."

In addition to suppressing the immune system response, the vaccine also significantly improved collagen content and bone quality — findings that suggests there could be long-term benefits following immunization.

Currently, rheumatoid arthritis is treated with steroids or medications that suppress the immune system, such as biologics and biosimilar drugs. While those therapies can alleviate pain and reduce inflammation, they can also make patients more vulnerable to infection and, in the case of biologics, are expensive. Biologic drugs can cost $25,000 a year.

“We have not made any really big discoveries toward treating or preventing rheumatoid arthritis in many years,” Chakravarti said. “Our approach is completely different. This is a vaccine-based strategy based on a novel target that we hope can treat or prevent rheumatoid arthritis. The potential here is huge.”

RA affects about 1.5 million Americans and about one percent of the global population. Women experience RA at a rate three times greater than men, have more severe symptoms and increased disability.

“In spite of its high prevalence, there is no cure and we don’t entirely know what brings it on. This is true of nearly all autoimmune diseases, which makes treating or preventing them so difficult,” said Chakravarti. “If we can successfully get this vaccine into the clinic, it would be revolutionary.”

Chakravarti and her colleagues have filed for a patent on their discovery and are seeking pharmaceutical industry partners to fund more research and preclinical trials.

Why Pain Is Not ‘All in Your Head’

By Gabriella Kelly-Davies, PNN Columnist

Anyone who lives with chronic pain knows it can affect their emotions. Every morning when I wake with a migraine, I feel a sense of doom. My heart races and I panic about how I will cope with everything that lies ahead of me that day — the meetings, deadlines and responsibilities, not to mention family and social commitments that often end up taking a back seat as I scramble to find ways of simplifying my day.

After decades of living with chronic migraine, I now know these emotions intensify my experience of pain. Having said this, I know it is not “all in my head” as some might claim, but part of a complex interaction between my emotions and the way my central nervous system incorrectly processes pain signals.

Exciting new Australian research using sophisticated brain imaging is shedding new light on what happens at an emotional level for people living with chronic pain.

Chemical “messengers” known as neurotransmitters facilitate communication between brain cells. Some neurotransmitters are inhibitory, helping to dial down our emotions, while others are excitatory and increase the intensity of emotions. A molecule known as γ-aminobutyric acid or GABA is the main inhibitory neurotransmitter.

Neuroscientist and psychologist Sylvia Gustin, PhD, discovered that GABA levels are lower in people with chronic pain and this affects their ability to regulate their emotions. The link between lower levels of GABA and chronic pain had been shown in animal studies, but Gustin’s research, recently published in the European Journal of Pain, is the first time it has been demonstrated in humans.

“A decrease in GABA means our brain cells can no longer communicate with each other properly,” explained Gustin, an associate professor at the University of Sydney’s School of Psychology. “When there’s a decrease in GABA, it makes it harder to keep emotions such as fear, worry, anxiety and depression in check.”

Gustin’s research shows there’s a physical change in the central nervous system that helps explain the roller coaster of emotions people living with pain often experience.

“If you live with chronic pain, it’s important to remember it’s not you -- there’s something physically happening to your brain. We don’t yet know why this happens, but we’re working on finding solutions on how to change it,” Gustin told me.

Her research confirms that chronic pain, which affects one in five people worldwide, is more than just an uncomfortable sensation. “It can affect our feelings, beliefs and the way we are,” she says. “Almost half the people living with chronic pain also experience major anxiety and depression disorders.”

GABA is not the only neurotransmitter that behaves differently in people living with chronic pain. In an earlier study, Gustin and her colleagues found levels of the main excitatory neurotransmitter in the central nervous system – glutamate -- are also lower in people with chronic pain. Lower glutamate levels are linked to increased feelings of fear, worry and negative thinking. They disrupt how brain cells talk to each other, affecting the ability to feel positive emotions such as happiness, motivation and confidence.

“My research results are reassuring for people living with pain because they show that physical changes in the brain are contributing to anxiety and depression and it’s not a person’s fault they struggle with these emotions,” Gustin said.

Her research team recently developed and tested an online recovery program that teaches people skills to help modify negative emotions such as fear, worry, anxiety and depression. The program helps to address the neurotransmitter disruption in chronic pain.

“Online programs offer hope to people living with disabilities or those in rural and remote communities who often struggle to access pain management services,” she said. “Online programs are also ideal during COVID-19 lockdowns.

“We know that chronic pain is always present, and we can’t get rid of it. But we can change the way we experience it by learning new skills. Like all skills, it takes practice to master it, but we hope it will offer another tool for people to change the way they experience pain.”

Gustin says preliminary results of this research, which will be published in a few months, are encouraging. Several organizations, including Australia’s National Health and Medical Research Council and Medical Research Future Fund, the International Association for the Study of Pain (IASP) and the U.S. Department of Defense, are helping to fund her work. To learn more about this research, click here.

Gabriella Kelly-Davies lives with chronic migraine.  She is the author of “Breaking Through the Pain Barrier,” a biography of trailblazing Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

The Inside Story of Elvis Presley’s Death

By Donna Gregory Burch

When Elvis Presley first hit the music scene during the 1950s, he was both beloved and vilified for the hip-thrusting, leg-shaking and gyrating that changed the art form of musical performance forever.

But what many don’t realize is that Presley’s ability to do those iconic dance moves came with a cost and may have actually contributed to his sudden death in 1977 at the age of 42.

In a new book entitled “The Strange Medical Saga of Elvis Presley,” Dr. Forest Tennant, a retired physician who specialized in pain medicine and addiction treatment, explores the fascinating medical history of Elvis.

Turns out, it wasn’t all those peanut butter, banana and bacon sandwiches that killed him. But what did?

I recently had a chance to interview Tennant about his latest book and what really caused Elvis’ death.  

Donna Gregory Burch: When I think about Elvis’ death, I recall the rumors that he died while taking a bowel movement on the toilet and that his autopsy revealed a very full colon. Are either of those stories actually true?

Forest Tennant: Yes, they are. We knew about these events [surrounding his death], but we had no scientific or medical explanation as to why they occurred. Fifty years after he dies, we finally have a scientific explanation as to why he died like he did.

What happened to him and why he died so suddenly in the bathroom was … a medical controversy that … ended up in a criminal trial and with all kinds of emotionalism.

Nothing happened to Elvis Presley that we don't have a good logical, scientific explanation for now. But certainly back in those days we didn't.  

You were involved in a court proceeding about Elvis’ death. Could you tell me about that and what role you served during the lawsuit?

Well, what happened was that because he died suddenly and because the pathologists couldn't agree on why he died, and because Elvis was found to be abusing drugs as well as being prescribed a lot of drugs, a criminal trial was brought against his physician (Dr. George Nichopoulos).

The attorney that decided to defend (Nichopoulos) was a man by the name of James Neal, who was a federal prosecutor who prosecuted Jimmy Hoffa and the offenders in the Watergate scandal, and so he was the nation's top attorney at that time. He investigated the case and found out that the doctor that treated Elvis Presley was not a criminal at all and was doing his best to help him.

Some dozen physicians at the Baptist hospital in Memphis saw Elvis Presley, but nobody knew what was the matter with him. They knew he had some kind of mysterious, systemic disease, which is a disease that can affect multiple organs at the same time.

He was a baffling medical case for the doctors in Memphis at that time, and we didn't know what he had up until about three or four years ago. We did not understand the genetic collagen connective tissue disorders, now usually referred to by doctors as Ehlers Danlos syndrome (EDS). Nobody understood that his glaucoma and his colon [issues] were connected [due to EDS]. They knew it was connected somehow but they didn't have an explanation for it at that time.

What do we know today about why Elvis died that we could not explain back when he actually passed away?

He had a severe heart problem.

Elvis’ heart problem was directly tied to his diet, right? I mean he was well-known for his fat and sugar-laden diet.

Yes, his diet was part of it, but his autoimmunity also affected his heart.

But the major controversy of the day is one that's maybe a little hard for the public to understand. A drug overdose in 1977 was said to only occur if the lungs filled up with fluid. He had no fluid in his lungs, so the only thing that he had at his autopsy of any significance was a huge heart. And so the pathologist and the county medical examiner said he had to have died of a heart attack because his heart was so bad.

The catch was that he had about 11 drugs in his bloodstream. The highest level was codeine, so there became a dispute among the doctors. A certain group of pathologists who were highly qualified said he died of a heart problem. Another group of highly qualified physicians who were called forensic pathologists said no, he died of his drugs. Up until about two or three or four years ago, the argument was still going on.

Now, I hate to say thanks to the opioid crisis, but because of the overdose deaths that have occurred in recent years, a lot of studies have been done, and enzymes have been discovered, and metabolism has been discovered showing that drugs like codeine can cause a certain heart stoppage without having pulmonary edema (fluid filling the lungs].

It turns out that 24 hours before he died, a dentist gave him codeine. He was already thought to be allergic to it anyway, and that was because he had all these metabolic defects due to his genetics, and so the codeine built up in his system. He had this terrible heart, so he died suddenly, within seconds, as he was trying to sit on the commode. He fell forward.

There is a forensic pathologist, the best one of the day, called Dr. Joseph Davis, and in about 1997, he described exactly, second by second, what happened to Elvis in the bathroom. But the cause is pretty clear: He took the codeine, and it caused a cardiac arrhythmia. If he had a good heart, he might have survived, but he had a bad heart.

So, it’s really a combination. You had these two sides of doctors arguing – they even ended up in a criminal trial – but it turns out that they were both right. It was a combination of a terrible heart and a drug that causes cardiac arrhythmia, and that's why he died with no pulmonary edema.

So many times in the medical community, we always look for that one cause, right? His case is very illustrative. Because the body is so complex, it's often multiple factors that are causing health issues.

Elvis Presley had multiple diseases. He was terribly ill, and he died accidentally in some ways with a dentist giving him codeine for his bad tooth, and his bad teeth were also part of the same disease that gave him a bad colon and a bad eye and a bad liver. They were all connected.

EDS is what connects all of those health problems, correct?

Yes, scientifically, EDS is a genetic connective tissue collagen disorder, and what that means is that you are genetically predetermined to have your collagen in certain tissues either disappear or deteriorate or become defective, and to put it bluntly, you can have a rectal problem and an eye problem at the same time due to the same cause because your collagen is deteriorating in these tissues, and you were programmed to develop this when you are born. It is a major cause of the intractable pain syndrome.

Now some of the diseases are very mild. You have a little double jointedness, and your skin is a little lax, and you might develop some arthritis, but you become a good gymnast in the Olympics or you become a good football player in some of the mild cases. But if you get a severe case like Elvis Presley, your life is going to be very miserable, and you're going to die young unless you get vigorous treatments, which are being developed right now.

I don't think EDS was even recognized back when Elvis was living, was it? It wasn't even a known diagnosis. Not many people even know about it today.

No, Dr. Peter Beighton didn't even come up with the (diagnostic screening tool for EDS) until long after Elvis Presley died.

As amazing as it may seem, I'm the only person in the United States who had the autopsies of both Elvis Presley and [aviator and businessman] Howard Hughes and their medical records, and was able to interview their physicians who took care of them. So I felt obligated to put these into books. I don't care whether anybody buys the books or not, but I do think these cases are marvelous cases, and I think these are icons and heroes of the last century, and somebody needed to write it down, and I'm the only one who had the material.

And you know something? For 50 years nobody cared that I had them. Maybe they still don't, but I've got them in the books now, so it'll be recorded for posterity, and that was my goal … to make sure that history is recorded.

Was EDS responsible for the way Elvis was able to move and dance?

Yes, we've got some pictures in the book, and I think we put the question in there. Can you hold these positions and sing and hold a microphone at the same time? And of course, [most people] can't. [EDS was] why he was able to do those things.

But on the other hand, we [recently had] the Olympics, and some of those Olympic [athletes] couldn't possibly do this if they didn't have these hypermobile joints. Whether they will develop the disease in later life is unknown.

When you're young, and you have these joints that are hyperextended, you can do things that other people can't do.

In your recent book about Howard Hughes’ medical issues, you had written about how Hughes was still very successful in life despite the fact he was in an enormous amount of chronic pain due to his medical conditions. Elvis was in the same predicament, wasn’t he?

Very much so, and I'm hoping that people who have intractable pain syndrome, who have EDS, complex regional pain syndrome, autoimmune diseases and traumatic brain injuries, read these books or at least hear about the books, and get some hope and realize that here are two men who did great things in very disparate fields but were terribly ill. I've had many, many patients who read about Howard Hughes tell me that he was an inspiration to them.

Elvis was in a great deal of chronic pain as a result of his EDS. Is that what led to his addiction to opioids?

Yes, we will never quite know how much of the drug taking that Elvis was doing was him self-treating his medical condition and how much of it was just abuse, but that's just the way it is. You can't quantitate it.

I was actually asked to deal with both of these cases because, back in the 1970s, I was trying to deal with patients who appeared to abuse opioids and other drugs and also had legitimate pain, and that's how I got involved with these cases.

It's an issue to this day, and society can't deal with it. They just refuse to talk about it, refuse to deal with it. You've got one group of doctors who just want to treat the addiction. You've got another group who just want to treat the pain, but you've really got to treat some of both and have doctors who understand both, but at this point in time, it's not happening.

I would love to see these books bring about some rational discussions about opioids and about pain and addiction, but I don't see it happening. I see nothing but controversy, accusation, falsehoods, fabrications. Society and the media can't seem to have rational discussions anymore about these issues, unfortunately.

I think with all of Elvis’ health issues and his subsequent drug addiction, it was almost like the perfect storm, right? He has EDS that's causing him extreme pain. The doctors give him pain medications to try to remedy that, so he can actually perform on stage, but then he’s still not able to perform up to the standards of his fans because of his addiction to those drugs.

He was really in a damned if you do, damned if you don’t predicament.

Yes. Also, these drugs probably caused him to have a terrible traumatic brain injury. We couldn't document it, but I suspect that's what happened. He did have a terrible traumatic brain injury, which accelerated all his other problems.

Yes. Apparently, he had fallen in a bathroom and had injured his head, and that was part of what was going on with him in the last years of his life as well.

Yes, it sure was. So again as you pointed out, it was the perfect storm. That's exactly what happened.

You know what I think is so interesting about these two books that you've written? We as the public have this view of Howard Hughes that he was a recluse because he was eccentric and that was just part of his personality. But he was actually really suffering a great deal from chronic pain.

And it's the same situation with Elvis. When we think about his death, we think he was just a drug addict who took too many pills one night, fell off the toilet and died, right? But Elvis was also living with extreme pain and suffering, and he was likely just trying to medicate himself out of that misery.

In our research studies, I saw four people yesterday who have EDS as well as spinal canal problems, and they're just miserable. I sometimes don't know how Elvis and Howard Hughes and the people I hear from daily, I don't know how they make it, you know? I marvel at it.

I'm hoping that everybody who's got intractable pain syndrome or EDS or traumatic brain injuries reads these books. That's who they're written for.

Why did you think it was important to write for those audiences?

I think that the audiences that we deal with are terribly neglected in society. I hate to say it, but I think people who have intractable pain are disdained by a great segment of the population. They're ignored by the political structure, neglected by the medical profession. I hate to say it, but the people we deal with, somebody has got to look after them.

My wife and I… we've managed to put together a foundation and use our business successes to try to help people, and I think that's not normal either. My study of the best physicians over time have been doctors who stepped up to the plate for people who needed it because nobody else in society is going to.

I feel sorry for all the groups that have been out lobbying their legislators, their politicians, their medical boards, and they get deaf ears. They get nothing but yes, yes, yes, but then nothing happens. The medical profession we have, it doesn't stand up for people with intractable pain syndrome or EDS, and that is because a huge part of the medical profession is based on treating well people or simple problems.

And so these are people in society who are disdained, neglected and abused, and are put in the corner by huge segments of not only society at large and the government, but also by the medical profession itself.

Yes, I understand exactly what you're saying. I've encountered it myself as a chronic pain patient.

I bet you do.

Any final thoughts?

I have read I don’t know how many books on Howard Hughes and Elvis Presley, and almost all of them are antagonistic. They are hostile. They blame somebody. They are looking for something that's bad, okay?

And I don't know whether it's the authors. I don't know whether it's their publishers. I can't tell you, except I know one thing: In my review of Howard Hughes and Elvis Presley, and like I say, I'm the last person who knew their doctors and had any real contact with their physicians and even the media, I don't see all this negativism.

I think people as a group try to deal with the Elvis affair legitimately, honestly and with care, and the idea that somebody should be blamed, somebody should be bad-mouthed, it's just not there.

These are great stories. They're tragic stories, but I think there are an awful lot of positive, really good things that happened to these men and to people who were around them, so I don't think we're going to get anywhere dealing with some of these issues with just total negativism.

And I think the whole situation, if you read it, is somewhat uplifting and motivating. We are here to try to help our fellow man and women have better lives, and I think there's a lot of that in both of these men.

Donna Gregory Burch was diagnosed with fibromyalgia after several years of unexplained pain, fatigue and other symptoms. She was later diagnosed with chronic Lyme disease. Donna covers news, treatments, research and practical tips for living better with fibromyalgia and Lyme on her blog, FedUpwithFatigue.com. You can also find her on Facebook, Twitter and Pinterest.

All proceeds from sales of “The Strange Medical Saga of Elvis Presley” will go the Tennant Foundation, which gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.

Widespread Pain Raises Risk of Dementia and Stroke

By Pat Anson, PNN Editor

Widespread body pain caused by fibromyalgia and other chronic pain conditions raises the risk of stroke and dementia, including Alzheimer’s disease, according to a new study.

Researchers looked at health data for nearly 2,500 second generation participants in the long-running, community-based Framingham Heart Study. Participants in the “offspring” phase of the study were given a comprehensive check-up that included a physical exam, lab tests and detailed pain assessment when they enrolled in the early 1990’s. They were then reassessed every four years for signs of cognitive decline, dementia or stroke.

Over the next two decades, 188 of the participants were diagnosed with some form of dementia and 139 had a stroke.

While the number of cases was small, researchers found an association between pain and cognitive decline. Participants with widespread pain were 43% more likely to have some type of dementia, 47% more likely to have Alzheimer’s disease, and 29% more likely to have a stroke compared to those without widespread pain (WSP). 

“These findings provide convincing evidence that WSP may be a risk factor for all-cause dementia, AD dementia (Alzheimer’s), and stroke,” researchers concluded. “While it is known that chronic pain or persistent pain without detailed classification is associated with poorer cognitive performance in cross-sectional or cohort studies, our study was based on much more accurate assessments for pain at a longitudinal population level. The specific presence of WSP… has long-term implications for dementia and AD.”

The researchers said there were three possible explanations for the link between pain and cognitive decline. First are lifestyle factors associated with pain, such as reduced physical activity, poor diet, alcohol and weight gain. Second is that stress caused by widespread pain may impair cognitive function; and third is that WSP may be a “preclinical phase” of dementia and AD.

Previous studies have also linked chronic pain to dementia. A large 2017 study found that older people with chronic pain experience faster declines in memory and are more likely to develop dementia. A more recent study suggests that people with chronic pain are at higher risk of memory loss and cognitive decline if they have lower levels of education, income and access to healthcare.

Antidepressants, anti-psychotics, antihistamines and other common medications may also cause confusion and disorientation that is mistaken for dementia, especially in older adults. When patients are taken off the drugs, their cognitive function may improve.  

Previous studies have also linked widespread pain to cancer, peripheral arterial disease, cardiovascular disease and increased mortality.