Muscle Relaxants Ineffective for Low Back Pain and Fibromyalgia

By Pat Anson

Muscle relaxants are increasingly prescribed “off label” as an alternative to opioid medication, but according to a new analysis they are no more effective than a placebo in treating fibromyalgia and low back pain. They may be beneficial, however, for patients suffering from muscle cramps, neck pain and trigeminal neuralgia.

Researchers reviewed 44 studies involving nearly 2,500 patients who were prescribed a muscle relaxant for various pain conditions. Nine skeletal muscle relaxants (SMRs) were assessed, drugs that were initially developed and then approved by the FDA as anti-spasticity and anti-spasmodic medications:

• Carisoprodol (Soma)

• Baclofen

• Tizanidine

• Cyclobenzaprine

• Eperisone

• Quinine

• Orphenadrine

• Chlormezanone

• Methocarbamol

Despite a lack of evidence on their effectiveness beyond 3 weeks, prescribing of SMRs doubled between 2005 and 2016, with office visits for refills of SMR prescriptions tripling over the same period, indicating they were increasingly being used long-term and off-label. According to a 2021 study, over a third of patients prescribed SMRs did not have a musculoskeletal disorder, a sign of “unnecessary or inappropriate use.”

Researchers involved in the current study, published in JAMA Network Open, reached a similar conclusion that muscle relaxants are overprescribed.

“Despite increasing prevalence and increasing risks of their use, our systematic review suggests only limited evidence of efficacy for long-term use of SMRs for a small subset of pain syndromes,” wrote lead author Benjamin Oldfield, MD, an Assistant Clinical Professor of Internal Medicine at Yale School of Medicine.

“Evidence for effectiveness was strongest for SMRs used for muscle spasms, painful cramps, and neck pain; in studies of SMRs for fibromyalgia, low back pain, headaches, and other syndromes, some showed small benefits and some did not, and on balance studies did not suggest a benefit.”

Oldfield and his colleagues say physicians should consider deprescribing SMRs to pain patients who have been using them long-term without apparent benefit.   

Adverse side effects from SMRs include sedation, somnolence, dizziness and dry mouth. The FDA also warns against taking the drugs with opioids, which could raise the risk of respiratory depression and overdose.

SMRs also increase the risk of falls, fractures, and vehicle crashes. Because of those risks, muscle relaxants should be avoided altogether in elderly patients, according to the American Geriatrics Society.

Why Autumn Weather Is Often Miserable for Pain Patients

Intellectually, I love the concept of a crisp autumn day. I love the idea of pumpkin spice lattes, crockpot chili, and cozy scarfs. But in practice, the intense temperature swings are pretty horrible for me every year.

The cool fall weather here in Northern Illinois is always devastating on my body. Indeed, my chronic pain has been 10/10 the last few days as the temperatures start their yearly drop, and it rains non-stop. 

It’s the same with spring too. Regardless of how much I’m longing for warmer weather every March, the shift from winter to summer means I spend most of the spring in too much pain to function. 

To me, it is obvious that these weather changes impact my pain. I’ve been dealing with it for more than a decade now. And every year, spring and autumn are especially bad. 

Surprisingly, the medical community still questions whether or not the link between weather and pain is real though – and if it is real, why it might be happening. 

“Research still hasn't confirmed a cause-and-effect link between weather and joint pain, though many people insist they can predict the weather based on such aches,” writes Toni Golen, MD, Editor in Chief of Harvard Women's Health Watch, in a 2022 article in Harvard Health,  

A 2015 study looked at whether daily weather conditions and changes in the weather influenced joint pain in older people with osteoarthritis in six European countries.

While they did find a causal link, they hesitated to call it a direct cause, saying that “the associations between day-to-day weather changes and pain do not confirm causation.”

In other words, researchers did not want to say outright that changes in the weather directly causes pain spikes. 

So I guess you’ll have to hear it from me instead: As a chronic pain patient, I can confirm that the effect is real, and it’s not in your head. Weather definitely causes pain spikes.

What might be causing it though? Golen explains that one theory is that changes in barometric pressure — which often happen as the weather changes — trigger pain in the joints. 

“Less air pressure surrounding the body can allow muscles, tendons, and other tissues around joints to expand,” she explains. “This can place pressure on joints, possibly leading to pain.”

Another theory is that cold, damp days make you more likely to do things that can worsen joint pain or stiffness, such as sitting on the couch too long watching movies. 

“Also, since you're expecting discomfort when the weather shifts, you may notice joint aches more than you would otherwise,” Golen adds. “To ward off weather-related joint pain, keep moving with regular exercise and stretching.”

I have to say, the second theory reads as a bit insulting to me. It sounds like health professionals are trying to find another way to blame patients for their pain. 

Personally, I also know that being sedentary is not the cause of my increased pain when the weather changes. That’s partly because when I wake up with pain in the morning, trying to shower and get out of the house quickly is likely to aggravate it. Also, as someone who works from home, I spend most of my days sitting down with a laptop and that usually doesn’t cause my pain to spike.  

As a chronic patient, I also don’t need a study to confirm my experience. I know weather changes cause a pain spike for me, and over the years I’ve learned to cope with it by accepting it. My life is set up so that most of the time, on bad pain days, I have the ability to rest as needed. 

When I first started having daily chronic pain, I would get very stressed about pain spikes, which would make them worse and harder to get under control. But now I know that keeping myself as calm as possible is the key to riding it out. 

I also know that it’s very likely that the pain will start to subside to more manageable levels after a couple of days at the most. And I know to take advantage of my low-pain days to get as much done as possible. In fact, I’m using one this week to write this column.

To me, the link between weather changes and pain spikes is so obvious, that I can’t even believe any doctors would still question it. If you’re among those struggling as the seasons change though, just know, I believe you. 

Can Ketamine Treat Fibromyalgia Pain?

By Pat Anson

At a time when the medical and recreational use of ketamine is coming under more scrutiny from law enforcement, a new study highlights its potential value as a treatment for fibromyalgia pain.

Ketamine is an anesthetic drug that is only FDA-approved for depression and anesthesia. But in recent years ketamine infusions are increasingly being used “off-label” for severe chronic pain conditions such as Complex Regional Pain Syndrome (CRPS).

In a small systematic review (a study of studies), researchers in Brazil found that ketamine infusions were safe and effective in relieving fibromyalgia pain. The review was small – just 6 clinical trials involving 115 patients – because ketamine has rarely been considered as a treatment for fibromyalgia due to its potency. Ketamine infusions require constant medical supervision because they put patients into a temporary dream-like state that can lead to hallucinations and out-of-body experiences.

But the Brazilian researchers found the side effects from infusions were mild and short-term, with some fibromyalgia patients experiencing pain relief that lasted for days or weeks.

Fibromyalgia is a poorly understood condition that causes widespread body pain, fatigue, insomnia, brain fog and mood disorders. The FDA has approved only three medications for fibromyalgia, two antidepressants (Cymbalta and Savella) and a nerve drug (Lyrica), but many patients consider the drugs ineffective.

Could ketamine be another option?

“Ketamine infusions might be a reasonable therapeutic approach for short-term relief of symptoms but unsatisfactory at inducing long-term analgesia in FM (fibromyalgia) patients,” the Brazilian research team reported in Advances in Rheumatology. “Future studies that evaluate the safety and effectiveness of ketamine in FM are desired for long-term follow-up. In patients refractory to conventional therapy, ketamine infusions might be a reasonable therapeutic approach.”

A recent case study suggests ketamine does have potential as a long-term treatment. A 68-year-old woman with fibromyalgia experienced “significant, widespread pain relief” after receiving several ketamine infusions over a two-week period. She continued getting infusions twice a week for the next year.    

“Pain relief has persisted under this regimen, along with a demonstrable improvement in quality of life, a reduced use of morphine, and the cessation of anti-depressant medication. This case indicates that long-term ketamine infusions show promise for chronic pain management and that more longitudinal studies on this treatment are warranted,” researchers reported.

‘Targeting and Investigating Doctors’

The positive news about ketamine is being overshadowed by the investigation into the death of actor Matthew Perry, who drowned in a hot tub last year after getting three ketamine injections in one day – none of them while under medical supervision.  Five people, two of them doctors, were recently arrested in connection with Perry’s death, including an alleged drug dealer known as the “Ketamine Queen.”

Perry had long struggled with substance abuse issues, but federal prosecutors say the defendants “were more interested in profiting off Mr. Perry than caring about his well-being.”  The two doctors charged in the case both surrendered their DEA licenses and can no longer prescribe controlled substances.      

In a recent appearance on CBS’ Face the Nation, DEA Administrator Anne Milgram likened Perry’s death to the opioid crisis, claiming that his doctors were ultimately responsible.  

“It started with two unscrupulous doctors who were violating their oath, which is to take care of their patients, and instead supplying Matthew Perry with enormous quantities of ketamine in exchange for huge amounts of money. And then it switched to the street where Matthew Perry was buying the ketamine from two drug traffickers,” Milgram said.

“Every single day, (we) are targeting and investigating doctors, nurse practitioners, others who are violating this duty of trust to their patients by over prescribing medicine or prescribing medicine that isn't necessary.”

Milgram also claimed that ketamine “has a high potential” for addiction. While experts agree the drug can be abused, ketamine is not an opioid and does not suppress respiration, the leading cause of an overdose.  

Can a Smartphone App Relieve Fibromyalgia Symptoms?

By Pat Anson

It was a little over a year ago that the FDA authorized the marketing of the first smartphone app designed specifically to treat fibromyalgia. The Stanza app uses a form of cognitive behavioral therapy (CBT) to help patients improve their quality of life by lessening the pain, anxiety, fatigue and depression that often come with fibromyalgia.

New findings from a placebo-controlled Phase 3 study, recently published in the The Lancet, helped demonstrate Stanza’s potential benefits.  

“This novel, non-drug therapy, available using a smartphone, makes management of fibromyalgia more accessible and convenient. This offers new hope for people with fibromyalgia, who have continued to experience unmet treatment needs,” says lead investigator Lesley Arnold, MD, an Associate Professor of Psychiatry at the University of Cincinnati College of Medicine.

Arnold and her colleagues enrolled 275 fibromyalgia patients in a 12-week trial, with half randomly assigned to receive Stanza treatment and the other half serving as a control group. Participants were allowed to continue taking medications and any other therapies they were using before the study.

Fibromyalgia is a difficult condition to diagnose and treat, because it comes with a wide array of symptoms such as widespread body pain, headaches, fatigue, insomnia, brain fog and mood disorders. The FDA has approved only three medications for fibromyalgia -- duloxetine (Cymbalta), milnacipran (Savella), and pregabalin (Lyrica) – but many patients consider the drugs ineffective or have too many side effects.

Stanza uses a form of CBT called Acceptance and Commitment Therapy (ACT) to teach patients psychological skills to help lessen the impact of fibromyalgia on their lives. A daily 15–20-minute session includes ACT lessons on deep breathing, mindfulness and other self-management skills.   

The effectiveness of Stanza was measured by the patients themselves, through a self-assessment test known as Patient Global Impression in Change (PGIC), in which participants described changes in their overall well-being.  

After 12 weeks, over 70% of participants in the Stanza group had improvements in their PGIC score, compared to 22% in the control group. Stanza participants also had more significant improvement in their pain intensity, physical function, fatigue, sleep and depression. No adverse events were observed either group.

It’s important to note the research was funded by Swing Therapeutics, the maker of Stanza, which calls it largest study ever conducted of a medical device for fibromyalgia.

“Fibromyalgia options are typically limited to a handful of pharmacological interventions that have limited efficacy and that can come with difficult-to-manage side effects,” says Mike Rosenbluth, CEO of Swing. “This publication validates Stanza as a guideline-directed non-drug approach that many patients previously couldn’t access due to few available trained clinicians, geographic limitations and cost.

Stanza is intended for use five to seven days per week, for a standard treatment period of 12 weeks. After that, Stanza can be used as needed. Previous studies have found that improvements in fibromyalgia symptoms can last up to 12 months after Stanza therapy.

Although it’s a self-guided app, Stanza requires a prescription and the supervision of a medical professional trained in its use.  Currently, Stanza clinicians are only available in the states of Illinois, Michigan, Missouri, Nevada, Ohio, Pennsylvania, Tennessee and Texas.  Medicare Part B and some private insurers cover Stanza treatment.  

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

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

‘Game Changing’ Study Finds Cause of Long Covid Brain Fog

By Pat Anson, PNN Editor

Inflamed and leaky blood vessels in the human brain appear to be the cause of brain fog and other cognitive issues in patients with Long Covid, according to a groundbreaking study by a team of Irish researchers.

The discovery that a viral infection may cause cognitive decline could help explain why memory loss, confusion and trouble concentrating is common in patients with other chronic illnesses, such as fibromyalgia, multiple sclerosis and chronic fatigue syndrome (ME/CFS).

Scientists at Trinity College Dublin and FutureNeuro used a specialized MRI to compare the brains of Long Covid patients with brain fog to those without brain fog.

The MRI images show how Long Covid can affect the brain’s delicate network of blood vessels. Patients with brain fog (right column) have significantly more inflammation and blood vessel leakage than those without brain fog (left column).

Patients with brain fog also had more elevated levels of glial fibrillary acidic protein (GFAP) in their blood, which is a sign of cerebrovascular damage often found in patients with repetitive head trauma.

The images and findings are published in the journal Nature Neuroscience.

“For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system, may be the key drivers of brain fog associated with Long COVID,” said lead author Matthew Campbell, PhD, a Professor in Genetics and Head of Genetics at Trinity College, and Principal Investigator at FutureNeuro. 

“The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game changing and is under active investigation by the team.” 

NATURE NEUROSCIENCE

About 10% of the people infected with the SARS-CoV2 virus develop Long Covid, a broad range of conditions that causes fatigue, shortness of breath, and muscle and joint pain. About half of Long Covid patients also report brain fog or some lingering neurological issue. 

“The findings will now likely change the landscape of how we understand and treat post-viral neurological conditions. It also confirms that the neurological symptoms of Long Covid are measurable with real and demonstrable metabolic and vascular changes in the brain,” said co-author Colin Doherty, Professor of Neurology and Head of the School of Medicine at Trinity, and Principal Investigator at FutureNeuro. 

In recent years, research has found that multiple sclerosis, lupus and other autoimmune conditions are triggered by the Epstein-Barr virus. The exact mechanism is unclear and proving there is a direct link between viral infections and brain fog has been challenging – until now.   

“Our findings have now set the stage for further studies examining the molecular events that lead to post-viral fatigue and brain fog. Without doubt, similar mechanisms are at play across many disparate types of viral infection and we are now tantalisingly close to understanding how and why they cause neurological dysfunction in patients,” said first author Chris Greene, PhD, a research fellow in the School of Genetics and Microbiology at Trinity.

The study was funded by Science Foundation Ireland, the European Research Council and FutureNeuro, a research center for chronic and rare neurological diseases.

My Story: Kratom Helps Treat Fibromyalgia

By Jim Hunter

The following narrative is not meant as medical advice. I am not a medical professional. I am simply relating my own experience.

Most of my adult life I have suffered from a variety of symptoms that were never diagnosed by any of the doctors I saw. Eventually, I became aware that these symptoms seemed to be consistent with the list of symptoms that appear under the heading of fibromyalgia. The most conspicuous symptom was painful muscles all over my body. The one symptom often associated with fibromyalgia that I did not have was insomnia.

Do I actually have fibromyalgia? I don’t know. What I have is an assortment of symptoms that, when compared to a checklist for fibromyalgia, make it look pretty close to that mysterious affliction.  Since there seemed to be no reliable objective signs of fibromyalgia, and I seemed to have almost all the subjective ones, it seemed reasonable to diagnose myself as having it.

I treated it for a long time (years) by taking more ibuprofen than is recommended for pain relief. The ibuprofen did help some, so I took more than I should have. I am not recommending anyone else do this, but I didn’t see an alternative at the time.

Then I discovered kratom. I don’t recall how I happened to run into it. But I discovered that when I took small doses of kratom regularly throughout the day, the fibromyalgia symptoms simply went away. Above all else, I didn’t hurt anymore.

Kratom even cleared up the stomach and intestinal problems. That was a surprise. I figured that anything that tasted as harsh as kratom wouldn’t help my stomach, but it did.

As long as I didn’t take too much kratom, I didn’t have any loopy feelings. I didn’t mind the slightly euphoric sensations it sometimes generated, but I learned to fine tune it so I didn’t experience that. It simply took away all the muscle aches and pains, fatigue and stomach problems. I felt normal again and was productive.

A Complication

That happy state facilitated by kratom lasted for years. But then I ran into a glitch. I got an inguinal hernia that strangulated. The surgeon was able to push it back in, but that was clearly just a temporary solution. Clearly, I needed surgery. One can die a nasty death from a strangulated hernia.

There was a complication about whether the local hospital could do the operation or whether my condition would require a bigger hospital with an intensive care unit. They eventually agreed on the local hospital (which is what I wanted), but the only glitch was that I had barely mentioned my use of kratom and sort of played it down. I was pretty sure most of the professionals in the medical field would be suspicious of it. Kratom is, after all, reported to have a mild opioid-like effect.

I’m 83 years old. I was perfectly willing to take any reasonable risk in surgery. I am not going to live forever, and I suspect that the end will not be decades off.

But I did feel obligated to the hospital that agreed to do the operation. I had to either level with them about the kratom I was taking or get off it. I knew that if I explained everything in detail, it would raise questions again about who should do the operation and when. I imagined there might be an issue with a possible interaction of kratom with anesthesia.

I decided to get off the kratom, at least long enough for the operation. There might be some withdrawal symptoms, but they were described in the literature as mild to moderate and short lived.

So, I began phasing out my kratom, for which I calculated I needed about two weeks. Two weeks stretched into three and then four. I was feeling horrible – considerably worse than what was described as kratom withdrawal. This was neither short, nor mild or moderate.

Then my wife put her finger on the problem. The symptoms for withdrawal and fibromyalgia, though similar, were not exactly the same. I was experiencing less nausea, but more pain. The fibromyalgia was back in full force. At that point, as I saw it, I had no choice. I took a little bit of kratom once again and felt fine, except for the hernia.

It was while on the minimal dose of kratom needed for the fibromyalgia that I went in for surgery. After the operation, the anesthesiologist reported that her part of the operation went well. I was relieved. However, another problem emerged. An expected two or three-hour operation with laparoscopic surgery turned into a seven-hour ordeal.

I still cannot visualize the exact nature of the unexpected problem the surgeon encountered. Apparently, my bladder was drawn into and tangled up with the hernia. The surgeon, who had done this operation thousands of times, had never seen it before and nobody else had heard of it.

The surgeon was able to unravel the problem and repair the hernia. This led to yet another problem. I had expected to be in the hospital most of one day, but they kept me in the hospital overnight and, as far as I knew, might keep me hospitalized even longer.

By three in the morning, I was beginning to experience moderate to severe pain. The medication given to me by the night nurse didn’t touch the pain. I realized I had no choice. I had to confess my sin -- the incomplete and unsatisfactory way I told them about the kratom -- and plead for mercy.

I called in the night nurse and explained the whole thing. She was very nice about it, let the head nurse know right away, and notified the surgeon as soon as he arrived in the morning.

To make a long story short, arrangements were made for me to be released from the hospital so I could resume my regime of small doses of kratom.

I had lots of minor aches and pains from being worked on so hard and so long during the operation, while in an awkward position. They had raised my legs a considerable angle to the ground, expanded the inner cavities of my body with CO2, and done God knows what to separate my scrotum, testicles and whatever else from the hernia. But with some Aleve, these were now manageable pains. 

Do I have any advice? Not really. The nearest thing I can offer is to say that, should the situation rise again, I would simply tell the medical people about my dependence on kratom. And if they insisted that I get off it before they would do the surgery, I would not have the surgery done.

Jim Hunter lives in Maine. He is a retired social worker.

Do you have a “My Story” to share?

Pain News Network invites other readers to share their experiences about living with pain and treating it.

Send your stories to editor@painnewsnetwork.org.

Long Covid Linked to Chronic Pain Conditions

By Pat Anson, PNN Editor

People with chronic pain conditions such as fibromyalgia, chronic fatigue, migraine and irritable bowel syndrome are significantly more likely to have symptoms of Long Covid after a COVID-19 infection, according to a large new analysis.

Researchers at the University of Michigan analyzed electronic health records of over two million Americans and found that the risk of having Long Covid symptoms was higher in people with a chronic overlapping pain condition (COPC).  

Over half the patients (58.6%) with a COPC and a diagnosis of COVID-19 had symptoms of Long COVID, compared to only a third (33.6%) of those without a COPC.

“We hypothesized we’d see an increase in pain and fatigue because it’s something we’ve seen in the past with other infectious diseases, like the SARS outbreak in 2002,” said lead author Rachel Bergmans, PhD, a Research Assistant Professor at U-M’s Department of Anesthesiology, Chronic Pain and Fatigue Research Center. “A big predictor of future pain is having had pain in the past.”

Findings from the retrospective cohort study, published in the journal Pain, do not establish a definitive cause that links chronic pain with Long Covid – only an association.

It’s a bit of a chicken-and-egg situation. Many of the symptoms of Long Covid mirror those of COPCs – such as brain fog, chronic fatigue, headache and body pain – so it’s not clear which condition developed first. Interestingly, Long Covid symptoms were found in 24% of patients with a COPC who were not diagnosed with COVID-19.  

That finding could be explained by a relatively new concept in pain research called neuroplasticity or nociplastic pain – chronic pain that lingers and becomes heightened in the brain and central nervous system (CNS) long after the initial injury heals. 

“With nociplastic pain, some people have what you might call a pain setting turned up in their central nervous system. There’s evidence showing that infections, trauma, and stress can be a trigger for nociplastic pain features and related symptoms,” said Bergmans.

Nociplastic pain could also explain the cognitive dysfunction and other symptoms caused by Long Covid – known technically as post-acute sequelae of SARS-CoV-2 infection (PASC). The basket of symptoms now collectively known as Long Covid may have existed before COVID-19 even came along. In 2022, the CDC estimated that 18 million American adults had Long Covid.

“The onset of long COVID features was relatively common regardless of acute COVID exposure. In addition, those with pre-existing COPCs had an increased risk of being diagnosed with long COVID features. These findings reinforce the likelihood that nociplastic pain is a key mechanism in long COVID and can inform precision medicine therapies that avoid the pitfalls of viewing long COVID exclusively in the framework of infectious disease,” researchers concluded.

“For clinicians who treat people with long COVID, it may be helpful to review the medical record and see whether someone had a pre-existing COPC diagnosis before long COVID onset.”

Bergmans and all of her co-authors are either consultants or employees of Tonix Pharmaceuticals, a company that is developing new non-opioid treatments for fibromyalgia.

Study Finds Low-Dose Naltrexone Works No Better than Placebo

By Pat Anson, PNN Editor

In recent years, low-dose naltrexone (LDN) has grown in popularity as a treatment for fibromyalgia and other chronic pain conditions. Although naltrexone is only FDA-approved for the treatment of substance use disorders, a growing number of patients and providers say low doses of naltrexone prescribed off-label can be effective in relieving pain.

A new study by Danish researchers is casting doubt on the some of those claims, finding that LDN works no better than a placebo in reducing pain for women with fibromyalgia. In their double-blind, placebo-controlled study, 99 adult women with fibromyalgia were randomly assigned to receive either an LDN pill or an identical-looking placebo daily for 12 weeks.

The study findings, recently published The Lancet Rheumatology, found a minor improvement in pain intensity for the LDN group, with a similar pain reduction in the placebo group. There were no serious adverse events in either group.

“This study did not show that treatment with low-dose naltrexone was superior to placebo in relieving pain. Our results indicate that low-dose naltrexone might improve memory problems associated with fibromyalgia, and we suggest that future trials investigate this further,” wrote lead author Karin Due Bruun, MD, a researcher in the Pain Center at Odense University Hospital in Denmark.

The Danish study is notable, because placebo-controlled, double-blind studies are considered the gold standard in medical research. Until now, much of the evidence about LDN has been anecdotal or low quality.

In a 2020 review of nearly 800 LDN studies, another research team could find only eight that were high quality enough to meet their criteria for evaluation. Nevertheless, they found that LDN “provides an alternative in medical management of chronic pain disorders.”

A 2019 review by British researchers also found that LDN is safe to use, but recommended that more clinical studies be conducted.

How naltrexone works is not exactly clear. LDN supporters believe the drug modulates the immune system, reduces inflammation and stimulates the production of endorphins, the body's natural painkiller.

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 have found LDN to be an effective pain reliever. PNN columnists have shared their positive experiences using LDN to treat everything from interstitial cystitis to Ehlers-Danlos syndrome to fibromyalgia.  

A woman with fibromyalgia tried all sorts of FDA-approved medications to relieve her leg pain, brain fog and depression. None worked, until she tried LDN.   

“After about seven days, my pain lessened,” said Janice Hollander. “[LDN] has completely changed my life. I don’t know that I would be here today if it wasn’t for it. I don’t think I could go for another year in the misery I was in.” 

Naltrexone does cause minor side effects, such as nausea and dizziness, and because it is an opioid antagonist it should not be taken with opioid medication.

Patients interested in trying LDN often encounter doctors who won’t prescribe it off-label. The LDN Research Trust includes a list of LDN-friendly doctors and pharmacies on its website.

Patients With Irritable Bowel Syndrome Have High Rates of Fibromyalgia

By Pat Anson, PNN Editor

A large new study has found high rates of fibromyalgia in patients with irritable bowel syndrome (IBS), adding to a growing body of evidence linking gut bacteria to chronic pain disorders. IBS patients were also more likely to have chronic fatigue syndrome (CFS).

The study, recently published in the journal Biomedicines, looked at more than 1.2 million IBS patients hospitalized in the U.S. over a three-year period. They found that the prevalence rate of fibromyalgia in the IBS patients was 10.7 percent, about five times higher than the fibromyalgia rate (1.4%) in the general adult population.

Fibromyalgia is a poorly understood condition characterized by widespread body pain, headaches, fatigue, insomnia and mood disorders; while IBS causes abdominal pain, cramps, bloating, gas and diarrhea. Gut bacteria has been associated with both IBS and fibromyalgia, but the exact mechanism of action remains unclear.

“This is yet another example where ailments in the gut are linked to ailments elsewhere in the body and mind,” said senior author Yezaz Ghouri, MD, an assistant professor of clinical medicine and gastroenterology at the University of Missouri School of Medicine. “As we continue to learn more about how gut health effects health elsewhere it is important that clinicians look for and manage somatic comorbidities in IBS patients.”

Fibromyalgia and CFS are known as “somatic” disorders because patients who have them often experience anxiety and depression – a tendency perhaps explained about the lack of effective treatments for their physical symptoms.

“Because IBS patients have higher prevalence of somatic comorbidities such as fibromyalgia and chronic fatigue syndrome, identifying and treating these disorders can improve their quality of life,” said lead researcher Zahid Ijaz Tarar, MD, a fellow in the division of gastroenterology and hepatology at the University of Missouri School of Medicine.

“Earlier identification of comorbidities is valuable to inform treatment strategies, including consulting other specialties such as rheumatology and psychiatry to improve the overall health outcomes in IBS patients.”

In addition to fibromyalgia, the research team found that hospitalized IBS patients were also significantly more likely to be white and female.  Less than one percent (0.42%) had a CFS diagnosis – a small percentage to be sure, but still higher than CFS rates in the general population (0.06%).

The high rates of fibromyalgia and CFS in IBS patients has led to speculation that poor diets or antibiotics may cause an imbalance of “bad” bacteria in the gastrointestinal system, allowing toxins to leak into the bloodstream and cause other health problems.

A recent study found that Klebsiella aerogenes, a bacterium that causes white blood cells to produce excess amounts of histamine, can trigger a painful immune system response.

Another study found that women with fibromyalgia have strikingly different types and amounts of bacteria than those without fibromyalgia. Faecalibacterium prausnitzii, a “good” bacterium that is normally abundant in the human gut, was found to be depleted in fibromyalgia patients. Other bacteria associated with IBS, CFS and interstitial cystitis were found to be abundant in fibromyalgia patients, but not in the healthy control group.  

Mood Disorders May Be Early Sign of Chronic Fatigue

By Pat Anson, PNN Editor

Anxiety, depression and other mood disorders have long been associated with fibromyalgia, irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS). That’s not altogether surprising, since the three chronic illnesses cause body pain, insomnia, fatigue, and other stressful symptoms that can trigger a psychological reaction. No one likes being sick, after all.  

But a large new study found that psychiatric disorders preceded the development of fibromyalgia, IBS and CFS in about a quarter of the people who have the conditions – more than those who suffer from similar chronic illnesses. Anxiety and depression were significantly more common in people who were later diagnosed with chronic fatigue.

"This work provides evidence that for many people, a wide variety of physical and psychological factors are associated with these debilitating conditions," says Francis Creed, a professor emeritus of psychiatry at The University of Manchester.

Creed analyzed over two years of health data from over 120,000 people who participated in the Dutch Lifelines cohort study; comparing the data of people with fibromyalgia, IBS and CFS to those with diabetes, inflammatory bowel disease (IBD) and rheumatoid arthritis. The latter group had similar symptoms and served as a control.

Creed’s findings, recently published in the journals PLOS ONE and Frontiers in Psychiatry, showed that psychiatric disorders were more common (17–27%) in the first group than in the control group (10.4–11.7%).

General anxiety disorder (GAD), panic disorder, dysthymia, major depressive disorder (MDD) and agoraphobia were particularly more common in people who were later diagnosed with CFS.  

PLOS ONE

Creed says a number of physical and mental health issues may be at work in the development of fibromyalgia, IBS and CFS. He favors a holistic approach to treating them, including a mental health evaluation.   

"When people suffering from CFS/ME, IBS and fibromyalgia come into contact with health professionals, negative attitudes can sometimes get in the way of treatment. but by understanding these complex conditions better, the stigma and mystery around them can be eased," he said.

"Although there are symptomatic treatments which may help these unexplained disorders, we should aim to understand fully their underlying causes. There are probably several different ways they may develop; a whole range of physical and mental factors are probably involved. Treatment approaches will become more effective as our understanding of the causes improves."

Association is not causation, and it’s important to note that about three-quarters of the people who developed fibromyalgia, IBS and CFS did not have any mood disorders prior to the onset of their illnesses.   

Creed says future research and clinical work should focus on possible interactions between psychiatric disorders and other behavioral variables to identify the true role of anxiety and depression in chronic illness.

FDA Authorizes Smartphone App for Fibromyalgia

By Pat Anson, PNN Editor 

The U.S. Food and Drug Administration has authorized the marketing of the first smartphone-based digital therapy for fibromyalgia. The Stanza mobile app doesn’t relieve the physical pain of fibromyalgia, but is designed to help patients manage the anxiety, depression and other psychological symptoms that often come with fibromyalgia.

Fibromyalgia is a poorly understood condition characterized by widespread body pain, headaches, fatigue, insomnia and mood disorders. The FDA has approved only three medications for fibromyalgia -- duloxetine (Cymbalta), milnacipran (Savella), and pregabalin (Lyrica) – but many patients consider the drugs ineffective or have too many side effects.

“This represents a major milestone both for our company and the fibromyalgia patients we serve, and is a big step towards meaningfully addressing patient access barriers by making evidence-based, non-drug treatments available to more people,” said Mike Rosenbluth, CEO of Swing Therapeutics, the maker of Stanza.

“On top of dealing with the debilitating symptoms, fibromyalgia patients have been historically underserved and even stigmatized. Current FDA-approved medications, while offering moderate efficacy, are often accompanied by side effects.”  

The Stanza app provides training in acceptance and commitment therapy (ACT), a form of cognitive behavioral therapy (CBT), to help patients develop flexibility and resilience in coping with fibromyalgia. ACT teaches mindfulness strategies and behavioral changes to help people accept and manage their pain.

In a clinical trial, Stanza significantly reduced depression and anxiety in fibromyalgia patients, while improving their quality of life. About 80% of patients responded to Stanza therapy and the benefits were sustained for up to 12 months.

Stanza is designed to be used five to seven days per week, for about 15 to 20 minutes a day, over a 12-week period. After 12 weeks, the app can be used as needed.

Stanza is only available by prescription. It was first made available last year under the FDA’s Digital Health Enforcement Policy for Digital Health Devices. Swing Care, an online clinic that provides personalized treatment of fibromyalgia, includes Stanza as an option for patients in Texas. Swing Therapeutics anticipates that Stanza will also be available through Swing Care in other states later this year.

We Need Better Treatments for Long Covid, Fibromyalgia, Chronic Fatigue and More

By Dr. Seth Lederman

Headlines about COVID have faded, and the United States will soon turn the page on public emergency status for the pandemic. The virus no longer dominates most of our lives, yet there are still thousands of new hospitalizations daily and an estimated 15 million Americans currently suffer from Long COVID.

The deep impact of long-haul cases has contributed to a surge of patients with disabling conditions, who are often misdiagnosed or treated ineffectively. More than one in five people infected with COVID-19 develop Long COVID and its constellation of physical and neurological symptoms. The persistent pain, fatigue, sleep problems and brain fog are similar to two other post-infectious syndromes, fibromyalgia and chronic fatigue syndrome (CFS/ME).

A recent study of both conditions and Long COVID documented that the physical and cognitive impairments of Long COVID were exacerbated in people previously diagnosed with CFS/ME or fibromyalgia. These types of chronic overlapping pain conditions have long been recognized by the National Institutes of Health (NIH), and the president’s National Research Action Plan on Long COVID similarly makes the connection between CFS/ME and Long COVID.

More than 50 million people struggle with these neurological illnesses every year in our country, and the burden of their chronic diseases comes at incalculable personal harm, along with billions of dollars in healthcare costs and lost productivity. 

There is one common denominator among all these unrelenting illnesses: the human brain. Physicians like me who study infectious and neurological diseases know that getting a drug’s active ingredients into the brain is not easy. Unlike biologic drugs, which are usually administered by injection, the only medications that can cross from the bloodstream into the brain are small-molecule drugs.

But big pharmaceutical companies have largely abandoned the development of new small-molecule therapeutics, instead pursuing biologic drugs which tend to be more expensive and profitable. That is because of a complex mix of federal laws granting longer market exclusivity to biologics, patent law changes that remove economic incentives to develop new small-molecule therapeutics, and mounting Food and Drug Administration hurdles.

Yet small-molecule drugs can be highly effective and life-changing, as well as relatively cost-effective to manufacture and distribute. They are our best hope for offering real relief to people struck by cruel conditions rooted in brain function.

As we pick up the pieces from a once-in-a-generation pandemic, we cannot ignore the rise in debilitating post-infectious diseases. In a sense, the people afflicted by these illnesses are living with invisible scars from the infections that preceded their current illnesses. There is an urgent need to help them by restoring incentives for small-molecule drug development and streamlining regulatory processes for new treatments.

The government should be accelerating efforts to expand its support for new drug therapies to address fibromyalgia, CFS/ME, Long COVID, and other illnesses that originate in the brain. The untapped potential of emerging therapeutics is unacceptable, as is the fact that many patients’ symptoms are frequently misinterpreted or dismissed.

It is good news that the Advanced Research Project Agency for Health has been established within NIH to pursue biomedical breakthroughs. But our country could still be doing more on this front. Congress has the power to legislate a more level playing field for small-molecule drug development, correcting decades of bureaucratic bias.

Lawmakers should appropriate more resources to fast-track clinical trials and scale-up delivery of novel therapies for post-infectious diseases. Public-private partnerships could also go a long way towards bridging the gap between treatments that would transform patients’ lives and their current limited options.

We know from our experience with COVID that medical science is capable of swift and significant breakthroughs. Our public health system should be equipped to readily diagnose and effectively treat people with fibromyalgia, CFS/ME, Long COVID, and similar devastating illnesses.

While the symptoms of these diseases are often not visible, our responsibility to provide patients with advanced and effective care is very real. For millions of Americans and their families, the time for better treatments is now.

Seth Lederman, MD, is a physician-scientist and CEO of Tonix Pharmaceuticals, a company developing technologies to treat Long COVID, PTSD, fibromyalgia, and other diseases.

Fibromyalgia Treatment Is a Real Gas

By Pat Anson, PNN Editor

Immersing fibromyalgia patients in high levels of oxygen is more effective at treating their pain and other symptoms than two medications commonly prescribed for the disorder, according to a new study.

Researchers at Tel Aviv University have been studying hyperbaric oxygen therapy (HBOT) for years as a possible treatment for fibromyalgia, a poorly understood condition characterized by widespread body pain, headaches, fatigue, depression and insomnia.  

Hyperbaric medicine is a form of treatment in which patients stay in a pressurized chamber and breathe 100% oxygen to help them heal faster. HBOT has long been used to treat infections, severe burns, carbon monoxide poisoning, and even scuba divers recovering from decompression sickness. The higher air pressure allows lungs to gather more oxygen than they would normally, and promotes the growth of new blood vessels and neurons in the brain.

In a 2015 study, researchers found that HBOT can also induce neuroplasticity in the brain and significantly reduce fibromyalgia pain.

"Until 15 to 20 years ago, there were doctors who believed that it was a psychosomatic illness and recommended that patients with chronic pain seek mental health care¸” said Shai Efrati, MD, of the Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center. “Today we know that it is a biological illness, which damages the brain's processing of the signals received from the body. When this processing is malfunctioning, you feel pain without any real damage in related locations.”

Efrati and his colleagues recruited 64 adults who suffer from fibromyalgia as a result of a traumatic head injury, and randomly assigned them to two groups.

One group was exposed to 100% pure oxygen in a hyperbaric chamber for 90 minutes, five times a week for three months; while the second group received either pregabalin (Lyrica) or duloxetine (Cymbalta), two FDA-approved medications for fibromyalgia.

The study findings, published in PLOS One, show that HBOT induced significant improvement in pain levels, quality of life, and emotional and social function. The clinical changes were correlated with increased brain activity in the frontal and parietal regions of the brain, which are associated with function and emotional processing.

A HYPERBARIC oxygen CHAMBER. 

"The results were dramatic," said Efrati. "At the end of the treatment, 2 out of 5 patients in the hyperbaric treatment group showed such a significant improvement that they no longer met the criteria for fibromyalgia. In the drug treatment group, this did not happen to any patient.

"In the group that received hyperbaric treatment, you could see the repair of the brain tissue, while in the control group there was only an attempt to relieve the pain -- without treating the damaged tissue -- and of course the medication group experienced the side effects associated with drug treatment.”

Duloxetine is an anti-depressant and pregabalin is an anti-seizure medication. Neither drug was initially developed to treat fibromyalgia, but were later repurposed as pain treatments.

"These drugs are not very effective,” said lead author Jacob Ablin, MD, from the Tel Aviv Sourasky Medical Center. "As a whole, existing treatments are not good enough. It is a chronic disease that significantly affects the quality of life, including young people, and hyperbaric medicine meets an acute need of these patients.”

Ablin says other non-pharmacological treatments are also beneficial for fibromyalgia, such as aerobic activity, hydrotherapy, cognitive-behavioral therapy and Tai Chi. He said quite a few patients request treatment with medical cannabis.

The studies are preliminary, and researchers say more long-term studies are needed to gauge the effects of HBOT after one, two and three years. But they’re encouraged by what they’re finding.

"This is a difference in approach: to cure instead of just treating the symptoms,” says Efrati. “Our goal as doctors is not only to treat the symptoms but to treat as much as possible the source of the problem, thus improving the quality of life of fibromyalgia patients."

Experimental Blood Test Could Improve Fibromyalgia Treatment

By Pat Anson, PNN Editor 

Finding effective treatment for fibromyalgia has always been problematic. The Food and Drug Administration has approved three drugs for fibromyalgia, but many patients find pregabalin (Lyrica), duloxetine (Cymbalta) and milnacipran (Savella) ineffective in treating the widespread body pain, fatigue, depression and “brain fog” that are common symptoms of fibromyalgia.  

A small pilot study suggests an experimental blood test for fibromyalgia – called FibroGENE -- could be used to determine which drug works best for each patient. Researchers at AMPEL BioSolutions and Duke University Medical Center found genetic biomarkers in the blood cells of 18 lupus patients with fibromyalgia-like symptoms. Their findings, published in the journal Lupus Science and Medicine, could lead to patients getting more effective, personalized treatment through genetic profiling.

“The bottom line is that we found the driving pathways for fibromyalgia that can be targeted by drugs that are already on the market,” said Amrie Grammer, PhD, Ampel’s co-founder and President.

“This is a disease management tool. This is meant for patients who know they have fibromyalgia, either on its own or in the context of another disease, such as lupus, and will be a game changer because treatment is often by trial and error. The doctor says, ‘Try this, let me know if it doesn’t work and try that.’ It often takes years, if ever, to get on a medication or medications that relieve the brain fog, the pain, etc.”  

Lupus is an autoimmune disease in which the body attacks its own tissues and organs, causing pain and inflammation. Like fibromyalgia, lupus is difficult to diagnose because its symptoms mimic those of other pain conditions. Genetic profiling of patients helps reduce the guesswork in treatment.

“The gene expression profiles of patients with fibromyalgia or type 2 lupus with fibromyalgia suggest both available drugs and new drugs that might be tested in patients with extensive pain and fatigue,” says study co-author David Pisetsky, MD, Rheumatologist and Professor of Medicine at Duke.

“Moreover, the gene expression profiles suggest a means to match patients with specific drugs. This opens a novel area of precision therapeutics for each individual patient rather than the trial and error approach currently employed.”

Larger studies are needed to prove the viability of Ampel’s blood test, but the company’s goal is to make FibroGENE commercially available by 2024 or 2025. Ampel is currently looking for fibromyalgia patients to participate in its clinical trials.