Fibromyalgia Update on
Doctors, Treatments & Research

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Developing fibromyalgia is like getting buckled into the seat of a never-ending roller coaster ride. There is no off ramp or way out. All you can hope for are compassionate doctors, effective treatments and research advances that make the ride smoother. No one questions the high prevalence of fibromyalgia, but what about your daily hassles? Here’s an update on important fibromyalgia issues and research progress that impacts your care.

Healthcare for Fibro

Most medical conditions pertain to a single organ or system in the body. This is not the case for fibromyalgia. Your symptoms involve multiple systems.

The diverse nature of fibro makes finding a good doctor essential, but who should you see? Rheumatologists developed the diagnostic criteria, yet a recent survey reveals that 90 percent don’t want fibromyalgia patients.¹ Perhaps a primary care physician is more suited. After all, these “generalists” are supposed to be trained to treat the whole body. However, the survey indicates only 38 percent of primary care doctors know how to diagnose fibromyalgia, much less treat it.

If you suspect that most doctors don’t want to treat fibromyalgia, this recent report confirms your suspicions. It’s a compilation of 20 different surveys and involves nine thousand physicians, so the findings are highly significant.

So, why are you being tossed between doctor’s offices like a human volleyball? The answer has to do with perceptions. Half of physicians believe fibromyalgia is a psychosocial condition, not a real disease.

Another survey of physician attitudes reveals that fibromyalgia carries a terrible stigma in the medical community.² Doctors confessed that if diagnosed with fibro, they would not disclose it to their colleagues. And in general, physicians said that treating your condition was not satisfying. Many providers claimed patients exaggerated their symptoms and others secretively hoped patients did not return.

Treatment Options

You know better than anyone – the treatments for fibromyalgia are disappointing. The number one endorsed therapy is exercise, which has downsides because overdoing it causes serious flare ups. Besides, research shows exercise does not phase the root cause of your fibromyalgia discomfort: reduced pain thresholds.³

Dare ask what the medical community and researchers promote as the second-best therapy for fibromyalgia? It’s cognitive behavioral therapy (CBT) or simply stated: learn to cope with your illness. Yet no surprise to you, a review of studies shows CBT provides only a six percent improvement in fibromyalgia symptoms.⁴ It helps you cope, but the physical benefits are imperceptible.

With regards to medications, you’ve no doubt already encountered their shortcomings. The three FDA-approved medications help one out of 7-10 fibromyalgia patients. And when it comes to alternative therapies, you are on your own to find help.

Research Offers Hope

Your physician and treatment dilemmas can be resolved if researchers identify the cause of your pain and develop biomarkers. Within the past five years, three findings possess a “wow” factor in fibromyalgia research and here’s a brief update:

• A marker that maps the widespread pain of fibro and documents inflammation throughout your brain.⁵ In fact, it tosses aside the old notion that your pain can be effectively treated with drugs that target neurons. Instead, the more likely target is the immune cells in your brain called microglia.
• Transferring blood from fibromyalgia patients to mice dramatically reduces the animal’s pain threshold.⁶ Fatigue and reduced grip strength also occurred in the mice. Something in your blood contributes to fibro and may lead the way to a diagnostic marker. Perhaps equally important, no one dares to suggest that these rodents need CBT or more exercise!
• Transferring gut bacteria from fibro patients to the intestines of mice also reduces the animal’s pain threshold.⁷ It even triggers the whole enchilada of metabolic and immunological findings from prior studies in patients. And another fascinating finding: depression occurred in the mice four months later (about ten human years). This clearly proves depression is not the cause of your disease.

The significance of the above discoveries is not lost on AFSA. Earlier this year, we funded three projects to build on the above findings:

• CES – evaluates the ability of this nondrug therapy to improve sleep, reduce fatigue, and decrease neuroinflammation
• Gut bacteria and Cannabis Trial – looks at the longitudinal changes in gut microbes with symptoms as well as the effectiveness of cannabis to treat fibro
• Brain-immune Interactions – assesses how immune markers in the blood affect brain function and fibro symptoms

AFSA has already solicited researchers worldwide and hopes to fund more patient-relevant projects in 2025.

The Real World

AFSA is laser-focused on funding projects with the greatest odds of impacting your care in the near future. However, we are not a large funding institution like the National Institutes of Health (NIH). We rely on donations while the NIH has a steady stream of tax dollars to fill their coffers. In 2023, the NIH claims they awarded $15 million towards fibromyalgia research.⁸ That’s impressive until you look at what they did with the money.

A breakdown of funds allocated by NIH shows one-fourth was diverted to study other conditions (see table). Another fourth went to fund more exercise and behavioral studies. Eight percent went to rodent models that had absolutely nothing to do with fibromyalgia.

Out of the 31 studies funded under the guise of fibromyalgia research, only three are good projects. One is a biomarker study. Another tests an old drug that shows promise. And the third project examines brain function in children initially developing fibromyalgia. 

Hoping to see more exciting studies funded by your tax dollars?  You generally won’t find a wow factor in NIH projects. Instead, they tend to reward the same researchers over and over again with their baby step approaches. While you are eager to see progress, scientists don’t have the same motivation. In addition, every researcher’s institution skims 30 percent off the top from each award for administrative services.  

There’s another facet of the NIH process you should be aware of. The higher-ups making the funding decisions are like the physicians who do not want to treat you. That’s why so much of the budget for fibromyalgia is diverted to other diseases, like arthritis and lupus. Even at NIH, there’s a stigma surrounding your illness. The assumption that you just need to cope and exercise regularly still prevails. 

You Deserve More

Whether you are work-disabled or hold a job, life is a constant struggle. Lack of physician empathy and ineffective treatments compound your burden of living with fibromyalgia.

Your greatest chance for a better life hinges on research, but not just any research. It must be innovative and focused on areas that improve your care sooner, not later. 

You cannot count on the NIH to fund innovative research that leads to effective treatments and disease credibility. The financial resources allocated to fibromyalgia in 2023 amounted to 8 cents per patient. 

AFSA doesn’t operate like NIH and here are four key distinctions:

• We do not allow any administrative overhead, and we greatly limit investigator salaries as well as equipment costs. Awarded projects must be budget conscious.
• Funded studies must have the potential to impact the lives of patients within the next five years. They need to be focused on treatments, or uncovering mechanisms that either lead to better therapies or diagnostic markers.
• We toss out applications that focus on exercise, psychosocial issues, or patient self-help. 
• We are an all-volunteer organization. Our only incentive to remain in operation is to come up with a cure … at the very least, biomarkers and effective treatments.

Unlike government institutions that feed off your tax dollars, AFSA relies on public support to fund studies. Our sole mission is to help patients get the quality care they deserve, but we need your help.

Make a Difference

While our website provides free patient education, money is required to accelerate the pace of research discoveries. Help us build on the successful momentum of recently funded projects. There are many ways to assist:

• Direct contribution (one time or monthly), either online or via check.
• If you, your significant other, or a family member is employed with a large corporation, ask about employer sponsored payroll giving programs. Many of these programs will also match donations. Companies may have their own system or they might use other programs such as Benevity, YourCause, or CyberGrants/Frontdoor … to name a few.
• In addition to employer sponsored programs, many companies use workplace giving platforms such as America’s Charity or Network for Good. It may be easier to donate tax-free a small amount through payroll deductions.

• Ask friends and family to donate in your honor in lieu of a holiday gift or birthday present. Our online and printed contribution form accommodates honorarium giving.

If you have a question about employer sponsored or giving programs, please email us at afsa@afsafund.org. The same holds true for donating securities.

If you or family members are concerned about AFSA’s credibility as a charity, we have a 4-star rating from Charity Navigator. We also have a Platinum Seal of Transparency from Guidestar/Candid, the largest nonprofit oversight organization in the world.

Fibromyalgia Research Update References

1.    Agarwal A, et al. Physicians’ knowledge, attitudes, and practices regarding fibromyalgia. Medicine 103:31(e39109), 2024. Free Report
2.    McGhie-Fraser B, et al. Validation of the Persistent Somatic Symptom Stigma Scale for Healthcare Professionals. J Clin Epidemiol. 174:111505, 2024. Free Report
3.    Lofgren M, et al.  The effects of a 15-week physical exercise intervention on pain modulation in fibromyalgia. Neurobiol Pain. 13:100114, 2023. Free Report
4.    Bernardy K, et al.  Cognitive behavioral therapies for fibromyalgia. Cochrane Database Syst Rev. 10(9):CD009796, 2013. Free Report
5.    Marker Maps Fibromyalgia Pain
6.    Is Fibromyalgia an Autoimmune Disease?
7.    Targeting the Gut
8.    NIH Report – Enter “Fibromyalgia” to get Research Funding for Fiscal Year 2023 

Marker Maps Fibromyalgia Pain

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A marker that maps painful body areas could validate the widespread nature of fibromyalgia. One promising molecule is TSPO (translocator protein).

TSPO appears on the surface of many immune cells, but only under certain conditions. It acts like a flag, signaling that the cell is actively fighting inflammation. Marco Loggia, Ph.D., from Harvard Medical School, discussed TSPO’s potential role in detecting inflammation and pain.* In particular, he described how researchers are testing this marker for mapping fibromyalgia and related chronic pains.

Neuroinflammation

To grasp TSPO’s significance, you first need to understand neuroinflammation. This term describes ongoing inflammation in the central nervous system (brain and spinal cord). The key players are glial cells, which are constantly on the lookout for any signs of danger. In healthy individuals, these cells quickly eliminate threats to the nervous system and then revert to their surveillance mode.

“Sometimes these immune responses become problematic,” says Loggia. “Activated glial cells continue unchecked even after the initial threat is resolved. They overstay their welcome and become harmful.” This leads to chronic neuroinflammation, which is linked to diseases like Alzheimer’s, Parkinson’s, and schizophrenia.

TSPO and Brain Imaging

Sampling brain tissue is too invasive. Alternatively, the brain can be imaged using PET (positron emission tomography). PET involves injecting a radioactive tracer that binds to TSPO, producing a signal on the brain scan. In healthy brains, TSPO levels are barely detectable. However, neuroinflammation increases TSPO production, which shows up as hot spots on PET scans.

Loggia studied painful conditions with evidence of neuroinflammation using PET to tag TSPO. Examples included fibromyalgia, low back pain, and migraines. The TSPO hot spots indicate activated glial cells, which may contribute to persistent pain. The location of the TSPO signal is particularly revealing.

Signal Locations

Loggia’s first PET studies using a TSPO tracer were performed on people with chronic back pain. Sometimes, patients showed a strong TSPO signal in the cortex, but not always. Loggia suspected leg pain was the driving force.

“Comparing patients with leg pain versus spinal pain, those with added leg pain showed a greater signal in the cortex,” says Loggia. He also assessed patients for their “fibromyalgia-like” score. The higher the score (more painful body areas), the greater the signal, particularly in the somatosensory region of the cortex.¹

“The somatosensory cortex contains a full representation of the body,” says Loggia. “Different parts of this cortical region process sensory inputs from different body parts.” For low back pain patients, “We saw a TSPO signal elevation in the cortex that matches the regional representation of back and leg pain.”

What about people with migraines? The TSPO signal appears in the cortical area representing the face/head.

Looking at fibromyalgia patients, Loggia says, ”We should see the whole somatosensory cortex light up because patients report widespread pain. And that is what we see.”² Indeed, Loggia’s finding was replicated by an AFSA-funded study.

No Sex Differences

TSPO is a marker on immune cells, and there are often differences in how the immune system works in men and women. However, Loggia did not see any sex differences in his low back pain studies.

Spinal Cord

So far, all studies relate to findings in the brain. Can TSPO pick up pain in the spinal cord? Yes, Loggia showed TSPO can detect areas of inflammation in the spinal cord of back pain patients.³ It also illuminated the surrounding structures, such as the nerve roots and the dorsal root ganglia (or DRGs). The DRGs contain the cell bodies of nerves just before they enter the spinal cord. While the DRGs reside outside the cord, they are enclosed by TSPO-producing glial cells. More importantly, the DRGs are implicated in contributing to fibromyalgia pain.

Peripheral Cells

“Wouldn’t it be wonderful to use the same marker to image inflammation in the brain, spinal cord, and peripheral tissues like joints?” asks Loggia. Since many immune cells produce TSPO, it might work as a marker outside the nervous system too.

Loggia tested TSPO’s ability to detect inflammation caused by knee osteoarthritis. He examined PET scans of people with and without knee pain due to osteoarthritis. Just like the “hot spots” in the brain that reflected inflammatory pain, the TSPO signal was intense for those with osteoarthritis. Loggia could also tell if patients had arthritis in one or both knees.

While knee osteoarthritis is not fibromyalgia, Loggia’s study reveals two important findings:

• The intensity of the TSPO signal is proportional to the level of knee pain.
• The TSPO signal strength correlates with the concentration of several immune substances in the blood.

This suggests that TSPO may detect pain and inflammation in tissues, although more studies are needed.

Treatment Response

If TSPO can pick up pain and inflammation, it might be useful for measuring physiological responses to treatment. Often, therapies for fibromyalgia don’t pan out because short-term improvements are fueled by hopeful thinking. A tool that objectively tracks improvements in pain after treatment is needed.

For example, in knee osteoarthritis, total knee replacement removes the source of inflammation, yet 30 percent of patients continue to experience pain. Loggia found that TSPO signals in the brain before the knee replacement helped predict response to the surgery.

The pre-surgery signal was more intense for patients who still had knee pain one year later. “This suggests that the TSPO signal we are measuring is not an epiphenomenon,” says Loggia. “It appears to have something to do with the establishment or maintenance of persistent pain.”

High-intensity signals in the sensory cortex reflect the “fibromyalgia-like” nature of the pain. These TSPO signals also depict the degree of neuroinflammation in the brain. As new treatments are developed for fibromyalgia, researchers might first put them to the “TSPO test” or something similar.

Beyond TSPO

Loggia highlights using TSPO as a marker for chronic pain and neuroinflammation. However, detecting TSPO using PET requires injecting a radioactive tracer, which is not ideal. Fortunately, new tools are being developed.

“Many groups around the world are looking at the concentration of brain metabolites believed to be linked to glial cell activity,” says Loggia. In fact, several research teams are focused on fibromyalgia. The next step will be to compare these metabolites with TSPO findings in the same patient. If a substantial overlap exists, these metabolites may be a suitable alternative. But for now, Loggia concludes, “The use of TSPO to image peripheral and central nervous system inflammation (and pain) is opening new doors.”

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1. Alshelh Z, Loggia ML, et al. Brain 145(3):1098-1110, 2022. Free Article
2. Albrecht DS, Loggia ML, et al. Brain Behav Immun 75:72-83, 2019. Free Article
3. Albrecht DS, Loggia ML, et al. Pain 159(5)968-977, 2018. Free Article

* Neuroinflammation: Does it have a role in human chronic pain? by Marco Loggia, Ph.D., presented at the International Association for the Study of Pain (IASP) World Congress, August 5, 2024.

Targeting the Gut
for treating fibromyalgia

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Your gut bacteria or microbiota form a living community that communicates with your brain. In fact, your microbiota exert significant control over your overall health. Five years ago, Amir Minerbi, M.D., Ph.D., of Israel published a groundbreaking study showing microbiota abnormalities in fibromyalgia.¹ Today, treating the gut microbiota in fibromyalgia represents a novel approach.

If studying your gut microbes seems off topic for fibromyalgia, see our article on Gut Influences. Ordinarily, the intestinal bacteria and central nervous system have a “healthy” relationship. But in people with fibromyalgia, the bugs living in the gut are different from healthy, pain-free people. New research by Minerbi’s team reveals that the altered microbiota are linked to fibromyalgia symptoms.²

Transferring Fibro to Mice

Transplanting the microbiota from fibromyalgia patients into the digestive tract of mice causes the animals to become pain sensitive. The process is called fecal microbiota transplantation (FMT).  Alterations in the mouse’s microbiota is linked to increased pain sensitivity during the first two weeks. Not only does the microbiota of the mice mimic that of the fibromyalgia patients, but the mice also develop fatigue. FMT from healthy people does not impact the mouse’s symptoms or microbiota.

Pain Precedes Depression

All too often, fibromyalgia is wrongly dismissed as depression or anxiety. The medical community calls these “affective traits.” Understandably, affective traits negatively impact a person’s health and contribute to reduced pain thresholds. However, it is frustrating for patients to be told that their fibromyalgia is caused by their state of mind.

To set the record straight, Minerbi selected fibromyalgia patients who did not have symptoms of depression or anxiety. “It was important to show that pain hypersensitivity is not mediated by affective traits,” says Minerbi. “The fact that pain is detectable in the mice days following FMT but depressive signs arise months later is a hint that pain precedes depression.” As a result, treating gut microbiota in fibromyalgia may reduce pain and prevent the mood disorders.

“The notion of ‘it’s all in your head’ or ‘fibromyalgia is a psychosomatic condition’ should be eliminated from the medical discussion,” says Minerbi. “Patients, families and clinicians need to know this.”

Altered Metabolism

Gut microbes can influence the production of pain-enhancing amino acids like glutamate and alter fat metabolism. The bacteria can also increase the production of bile acids that cause pain, rather than relieve it. These unwanted effects are well-documented in people with fibromyalgia.  And it turns out, the mice receiving FMT develop the same metabolic abnormalities as the patients. Quite possibly, treating the gut microbiota in fibromyalgia patients can decrease glutamate and lead to reduced pain.

The mice didn’t just have increased glutamate in their blood, the concentration of this pain transmitter was also elevated in the central nervous system. This goes to show that transferring microbiota into the gut significantly impacts brain function.

Immune Changes

Your intestines are lined with immune cells. In addition, lymph and a variety of immune cells surround your digestive tract. If the microbiota in the gut is altered in an unhealthy way, the immune system might become actively defensive. This angle was explored by Minerbi’s colleague, Arkady Khoutorsky, DVM, Ph.D.*

Looking at the numbers of immune cells in the blood of mice, Khoutorsky found the memory B cells were nearly depleted. Memory B cells help your immune system remember prior exposures of potentially threatening agents. If the agent enters your body again, your memory B cells pump out antibodies to neutralize the threat. Khoutorsky did another test that showed increased activation of the immune system. 

People with fibromyalgia have activated immune cells in their brain called microglia. Minerbi found these same cells to be on guard in the brains of mice exposed to fibromyalgia FMT. To measure the microglia’s role, he blocked their activation with a medication prior to the FMT. The ability of fibromyalgia microbiota to produce pain sensitivity was greatly reduced. “These results indicate that the development of pain after fibromyalgia FMT is partially mediated by the microglia.”

The Neurons

Most fibromyalgia patients will say their skin burns, their muscles ache, and their brain function is dulled (e.g., fibrofog). It’s hard to believe that the far-reaching effects of fibromyalgia are solely due to malfunctions in the brain and spinal cord. Conversely, if the muscles were the source of disease, how would one explain the common symptoms of fibrofog and sleep disorder?

Prior studies show a misbehaving immune system targets the dorsal root ganglia (DRG) to amplify pain transmissions. But other neurons are also affected. “The DRG is an attractive target,” says Minerbi. “But in our study, there are changes in all levels of the pain-signaling pathways. The peripheral small nerve fibers, the DRG, the spinal cord, and the cortical structures in the brain are all involved.” At least, this is what Minerbi found in the mice when he looked at the effects of FMT from fibromyalgia patients. So, the neurons at all levels of the nervous system may be contributing to your symptoms. 

But how can you relate this finding to the bugs growing in your intestines? Disruption of your gut microbiota leads to activation of your immune system. After all, the immune cells lining your intestinal tract are programmed to protect you from foodborne pathogens. If the bacteria in your gut changes composition, they can also set off alarms targeting all levels of your nervous system. So, treating the gut microbiota in fibromyalgia patients can mute the immune system and reduce pain signals transmitted by the neurons.

FMT in Fibro Patients

A small trial of FMT from healthy subjects to fibromyalgia patients led to a 30 percent reduction in pain. But just doing the FMT alone did not work. Patients had to be given antibiotics before the ten-week trial (five transfers every two weeks).

“The microbiota in the gut is a stable environment,” says Minerbi, “and it’s resilient to transient perturbations. The amount of bacteria we give in FMT is many orders of magnitude smaller than that of the established microbiota in the gut.” So, antibiotics are given to clear out the existing bacteria and allow the transplanted bacteria to take hold.

Based on the success of this small trial, a large placebo-controlled study is underway. Minerbi’s team will be looking at which bacteria improve the most, in addition to alterations in the metabolic and immune system variables.

“We hope this will help explain why certain fibromyalgia patients respond better than others,” says Minerbi. “We also want to identify the biological mechanisms responsible for symptom improvements.”

Designer Treatments

Even if FMT turns you off, it provides much-needed answers from a research perspective. Perhaps the greatest downside of FMT is that it cannot be commercialized. Minerbi points out that some companies already have FDA-approval for microbiota-based therapeutics. Basically, these companies aim to develop specially formulated probiotics to treat illnesses like fibromyalgia.                               

“We aim to identify the bacterial species that are critical for effective fibromyalgia treatment out of the hundreds that are given during FMT,” says Minerbi. “Then these species can be developed into future therapy for the disease. Since fibromyalgia is a diverse condition, there may need to be more than one formulation.” Indeed, treating the gut microbiota in fibromyalgia patients may be tailored based on one’s microbial composition.

In the Meantime …

If you are tempted to purchase multiple probiotics to tame your fibromyalgia symptoms, press the pause button. Hundreds of bacterial species live in the gut but only a few are contributing to your symptoms. On the other hand, Minerbi says that the probiotics on the market do not contain any species suspected to be involved in the disease. You are also up against the fact that your existing microbiota community is resilient to change.

It’s frustrating to know that a disruption of your microbiota is likely linked to your symptoms, but you can’t just correct it with probiotics. Until designer treatments become available, Minerbi recommends a low-sugar and gluten-free diet, exercise regularly, and get plenty of sleep. See Diet & Nutrition for assistance. These measures are known to help maintain a healthy community of gut bacteria.

Research takes time, and this is frustrating to hear. But keep in mind that seven years ago the microbiota was not known to be involved in fibromyalgia. “The results are promising, so there is hope on the horizon,” says Minerbi.

AFSA funded three projects this year, and one award went to Dr. Minerbi to expand his amazing research.  Help us fund more studies in 2025.

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*  Minerbi’s team of collaborators include Yoram Shir, M.D., Arkady Khoutorsky, DVM, Ph.D., and Emmanuel Gonzales, Ph.D., of McGill University in Canada and Nicholas Bremerton, Ph.D., of University College in Dublin.

1. Minerbi A, et al. PAIN 160:2589-2602, 2019. Free Abstract
2. Cai W, Shir Y, Minerbi A, Khoutorsky A, et al. BioRxiv Oct 28, 2023. Free Report

Exercise Difficulties in Fibromyalgia

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Exercise floods the body with feel-good endorphins, clears the mind, and ramps up the cardiovascular system. It’s invigorating, unless you have fibromyalgia. The processes controlling cardiovascular workouts do not work correctly, causing exercise difficulties in fibromyalgia patients.

Dane Cook, Ph.D., of the University of Wisconsin, says, “People with fibromyalgia show an abnormal response to gentle exercise.” ¹ According to a report by Bruno Gualano, M.D., of Brazil, fibromyalgia patients do not accelerate their heart rates adequately during increased activity.² And a study by Jose Parraca, Ph.D., of Portugal, shows that the oxygen supply to the muscles is impaired (even at rest) in patients.³ In fact, all three reports explain why you have problems exercising with fibromyalgia.

The above studies highlight a variety of reasons why you encounter difficulties with overexertion. Yet, understanding what you are up against will help you tailor activities to accommodate your dysfunctional response to exercise.

System Controllers

Control of heart rate is based on input from two different nerve branches: your sympathetic (fight or flight) and your parasympathetic (rest and digest). Together, they make up your autonomic nervous system—it’s the network of nerves that communicate between your spinal cord and your peripheral tissues (e.g., your muscles and organs).

To ensure your organs respond appropriately to any challenge, your nervous system must be responsive and flexible. The control dials for either branch must be capable of going from zero to zoom in a split second. Let’s face it, your environment and activity levels are constantly changing, so a flexible autonomic system is essential.

The diagram shows how the two opposing on/off inputs from your sympathetic and parasympathetic nerves control your heart rate. Think of it like two kids on a seesaw that works best if balanced (i.e., both children weigh the same). Yet the timing from one lift off to the next varies, just like your heartbeat, because the system has built-in flexibility.

If you dash out of a burning house, your adrenaline-controlled sympathetic branch should kick in to get your body moving and your heart pumping. If you are digesting your dinner or trying to fall asleep at night, the calming actions of your parasympathetic branch should take over.

Low Heart Rate

People with fibromyalgia have too much sympathetic nervous system activity, even when relaxing.⁴ Mild challenges to the body, such as standing up or being exposed to cold, may also lead to unwanted symptoms. When switching from reclining to standing, your heart should pump more blood to the brain to prevent lightheadedness. Exposure to cold requires increased circulation of warm blood to your extremities to prevent Raynaud’s-like symptoms (painful spasms in the hands and feet).

Reduced heart rate in response to exercise is a risk factor for cardiovascular disease. This prompted Gualano to look at the differences in cardiac functions between fibromyalgia patients and healthy controls during exercise. Not only did he measure the heart rate at peak exercise capacity, but he also looked at how fast the heart slowed down after ceasing activity. Ideally, the heart rate should increase rapidly to adjust to the body’s physiologic demands, but once resting, its rate should drop quickly.

“Fifty-seven percent of the fibromyalgia patients exhibited slow heart rate response to exercise, but none of the healthy controls,” says Gualano. “The reduction in heart rate was also slower in the fibromyalgia group during the two minutes post-exercise.”

Why was the heart rate so low in people with fibromyalgia? Gualano says, “The autonomic nervous system is not as flexible as it should be.” Activity ought to prompt the sympathetic system to get the heart pumping while forcing the calming parasympathetic branch to withdraw control. The reverse should occur during rest, yet an imbalance called dysautonomia exists, causing exercise difficulties in fibromyalgia.

The cause of dysautonomia remains unclear. Gualano emphasizes the sympathetic system is super-charged at rest and unresponsive when challenged. A hyperactive sympathetic system leads to a chronic pounding on the receptors in the heart that help regulate how fast it beats. After a while, these receptors become indifferent to the sympathetic system’s demands, which makes the heart less responsive to activity challenges.

Fibro is to Blame

Could Gualano’s finding be due to a lack of exercise or a reduced fitness level? Or could symptom severity play a role? The answer is no, based on two reports from another Brazilian team.

The first study compared fibromyalgia patients to healthy controls who were matched for their level of physical fitness.⁵ Despite the same fitness levels, the fibromyalgia group had a reduced heart rate response to an exercise challenge. The speed at which their heart rate returned to resting levels was also slower. In addition, measures of autonomic nervous system function revealed an imbalance between the sympathetic and parasympathetic branches.

The above findings run counter to what is known about exercise and fitness levels, at least in healthy people. When a healthy person becomes sedentary, their sympathetic and parasympathetic systems become unbalanced, but they can correct this with exercise. So, the same research team sought to answer another question: could the dysautonomia in fibromyalgia be related to symptom severity?

Dividing fibromyalgia patients into two groups based on symptoms, moderate and severe, they compared fitness measures and autonomic functions to a healthy group.⁶ Although the level of physical fitness was worse for the severe fibromyalgia group (compared to the moderate), their autonomic nervous system function was equally impaired. 

What does this mean for you? Lack of exercise or symptom severity do not appear to contribute to your level of dysautonomia. In fact, the sympathetic dominance with reduced parasympathetic activity is likely adding to your fibromyalgia symptoms, rather than being the result of inactivity.

Altered Response

If exercise does not increase heart rate appropriately, what about the rest of your cardiovascular system? Cook’s team looked at how this system worked in fibromyalgia patients (compared to controls) while performing mild exercise. He found the heart pumps harder during exercise in fibromyalgia patients, and the rest of the cardiovascular system doesn’t keep up.

“These results indicate that exercise for fibromyalgia patients is more difficult than for healthy individuals on many levels … but it doesn’t mean that increasing physical activity won’t help some of these abnormalities.”

Muscles Lack Oxygen

To increase delivery of oxygen and nutrients to your muscles, your sympathetic constricts blood vessels to speed up the flow. However, your parasympathetic is responsible for relaxing or expanding the arteries so that a larger quantity of blood can be delivered.

Given the studies showing an overpowering sympathetic system with inadequate parasympathetic activity, are your muscles getting the oxygen they need? No.

Parraca’s team in Portugal assessed the amount of oxygen delivered before, during and after exercising the thigh muscle in fibromyalgia patients and healthy subjects. The healthy group showed an increase in oxygen consumption during the exercise, while there was virtually no change in the patient group. Even at rest, the oxygen supply was significantly less and contributing to exercise difficulties in fibromyalgia.

Another finding by Parraca’s team shows that people with fibromyalgia experience a 50 percent drop in saliva secretion during exercise.⁷ Why is this important? Saliva flow is controlled by your parasympathetic system, and its dramatic decline is a sign of dysautonomia. It also explains why you may develop dry mouth when you exercise or overexert yourself.

Staying Active

Intense exercise will set you back, so the best you can do is move regularly at your preferred pace. If you maintain your own natural speed (which is much slower than healthy people), energy consumption is optimized. Moving too fast or vigorously may force your muscles to operate without enough oxygen and lead to more symptoms.

Another study shows that a self-paced program (on land or in the water) leads to slow improvements in speed over two to three months.⁸ Benefits in physical function take time. Any attempts to rush progress will likely lead to problems exercising with fibromyalgia.  However, if you can keep up a slow and steady pace, you may also notice improved coordination and cognition.

One more point: make use of warm water. Heat invokes the parasympathetic system to relax your blood vessels to help your muscles receive more oxygen and nutrients. In addition, you have heat sensors in your tissues that work to help relieve pain. If you are struggling with an exercise program, warm water therapy may be the solution for you. If this is not feasible, try taking a hot shower or bath just before working out. Alternatively, you might purchase a portable hot tub. If you get a four-seater, you can do gentle stretches in the center before doing land-based exercises.

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References for Exercise Difficulties in Fibromyalgia

1. Cook DB, at al. Med Sci Sports Exerc 44(6):1186-93, 2012.
2. Da Cunha Ribeiro RP, Gualano G, et al. Arthritis Res Ther 13:R190, 2011.
3. Villafaina S, Parraca JA, at al. Biomedicines 11:132, 2023. Free Report
4. Lerma C, at al. Arthritis Ther Res 13:R185, 2011.
5. Schamne JC, et al. J Clin Rheumatol 27(Suppl 2):S278-S283, 2021. Abstract
6. Sochodolak RC, at al. J Exerc Rehabil 18(2):133-40, 2022. Free Report
7. Costa AR, Parraca JA, at al. Diagnostics 12:2220, 2022. Free Report
8. Tiinus PM, at al. J Sports Sci Med 1(4):122-27, 2002.

Giving LDN Your Best Shot

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Need a roadmap on how to test drive low-dose naltrexone (LDN) for fibromyalgia? This article offers navigation advice from four experts to minimize the bumpy road ahead. If you have not heard of low dose naltrexone, check the trial funded by AFSA. Basically, LDN works to quiet the immune cells in the central nervous system (the microglia) that are magnifying your symptoms. The side effects of LDN are mild. All other drugs prescribed for fibromyalgia target the neurons and cause a slew of side effects.

Success Rate

What are the odds that LDN benefits you? Sean Mackey, M.D., Ph.D., a pain specialist at Stanford University in Palo Alto, CA, was one of the investigators on AFSA’s LDN trial. He found that three out of ten patients achieved at least a 30 percent improvement in pain.¹ The drug produced similar benefits in fatigue and sleep, but the study included only 30 people.

Nicholas Aitcheson, M.D., a rehabilitation and pain specialist in Queensland, Australia, says, “Around 200 patients have tried LDN for fibromyalgia in our chronic pain clinic. Anecdotally, one-third reaped significant positive results in pain reduction and improved function.” Reports by other pain clinics involving anywhere from ten to 70 fibromyalgia patients give similar findings.

Symptoms LDN Treats

Aside from pain, LDN helps with cognition (reduces brain fog), sleep, mood, and fatigue. “Fatigue is a major complaint for people with fibromyalgia,” says Mackey, and it’s difficult to find anything to alleviate this symptom. Pain specialist Michael Fishman, M.D., of Lancaster, PA, adds that LDN also reduces postural hypertension (lightheadedness upon standing) and burning symptoms. While not every patient has these problems, they are tough to treat.

“When choosing patients for a prescription of LDN, I like to ensure that they have fibromyalgia and not just pain in a few areas,” says Aitcheson. “The presence of other symptoms like cognitive clouding, fatigue and unrefreshing sleep shifts me toward the use of LDN.”

Must Be Compounded

LDN appears to work as well, if not better, than other drugs to treat fibromyalgia. Unfortunately, your local pharmacy only dispenses 50 mg tablets of naltrexone. To get the tiny dose needed, you must go through a compound pharmacy. Insurance companies won’t pick up the tab, but the cost of LDN is $1/day … and possibly less.

“Some patients and physicians may be nervous when using a medication that needs to be compounded,” says Aitcheson. To ease concerns, he points out, “Naltrexone has been used safely for at least 40 years and we are prescribing it at less than one tenth of the minimal normal dose.”

Working with a compounding pharmacy sometimes presents hurdles for patients and physicians. However, Anne Marie McKenzie-Brown, M.D., a pain specialist at Emory University in Atlanta, GA, offers advice on Compounding Pharmacies in the last section.

Dosing LDN for Fibromyalgia

The most common dose of LDN is 4.5 mg/day, but the range is from 1.5 to 9 mg.² Just like all medications, one dose doesn’t work for everyone. Fibromyalgia patients usually take LDN as a single dose at bedtime because if side effects occur, they won’t impact daytime function.

“I just recommend that patients start at 4.5 mg at night,” says Mackey. “I don’t think that there is anything magical about that dose.” This was the dose used in the fibromyalgia trial and it happens to be the average dose patients end up taking.

According to Fishman, “If nightmares or vivid dreams are present, they improve with taking LDN in the morning instead of the evening.” Other side effects, such as headaches, nausea and anxiety are mild and occur infrequently. However, if they persist, you can drop down to a 3 mg dose and these side effects will usually go away. 

If you are drug sensitive, other dosing schedules may be used. “I start patients at 1.5 mg/day for the first week, increase it to 3 mg/day the second week, and move patients to a stable dose of 4.5 mg/day the third week,” says Aitcheson. He prescribes 1.5 mg compounded capsules during the titration phase.

McKenzie-Brown uses a similar titration schedule, but instead of capsules, she prescribes 3 mg tablets that are scored. This form of LDN is available from a few mail-order pharmacies. “I start with 3 mg tablets and ask patients to cut them in half for one to two weeks to make sure there are no side effects. Then they go to 3 mg. If they have relief and want to stay at 3 mg, we stay at this dose. Otherwise, I have patients increase to 4.5 mg. Many patients stay at 3 mg.”

Be Patient

Low dose naltrexone is not a fast-acting treatment. Patients in the LDN trial for fibromyalgia trial took a month to notice improvements. Both Aitcheson and McKenzie-Brown recommend being on LDN at 4.5 mg/day for three months before giving up. In fact, McKenzie-Brown published a study on the use of LDN at her chronic pain clinic.³ She noticed 12 percent of patients don’t get pain relief until after three months.

“I ask patients to reserve judgement on LDN efficacy until the end of three months,” says McKenzie-Brown. “Many patients have told me that they would have stopped LDN, but they are glad they did not.”

Complimentary Therapies

Getting a handle on fibromyalgia requires a combination of therapies, so don’t view LDN as your only option. “I usually prescribe LDN as an add-on to other medications,” says Aitcheson. He recommends magnesium and duloxetine along with LDN. “These agents act on the pain amplification pathways in the brain and spinal cord.”

McKenzie-Brown refers patients to physical therapy, aquatic therapy, and acupuncture, in addition to prescribing nonopioid medications. The point is you don’t have to wait for LDN to work to get relief from your fibromyalgia.

Increasing the Dose

If LDN is reducing your symptoms, it’s natural to wonder if a higher dose might be better. “I take it on a case-by-case basis,” says Mackey, adding “there aren’t any guidelines to direct us in this phase.”

“For the vast majority of people,” says Aitcheson, “going above 6-8 mg per day is not likely to be worth it.” Trying a higher dose requires a new script, so talk it over with your physician at a follow-up visit.

Will LDN Stop Working?

It’s possible, but physicians seldom encounter patients who develop tolerance to low doses of naltrexone.

Drugs that target the neurons (particularly the receptors that produce transmitters) often lead to tolerance. Returning the microglia to their normal resting state should not cause tolerance, but no one knows for sure.

“Lifestyle measures (exercise, sleep, diet, etc.) must be put in place when the effect of LDN is good,” says Aitcheson. “This strengthens people’s reserve, so if LDN stops working, it won’t be so devastating.” He also points out that patients may not be experiencing a loss of LDN efficacy, but rather a fibromyalgia symptom flare.

LDN and Opioids

Naltrexone blocks the action of opioids, so should you abstain from taking this class of meds while trying LDN? Maybe not if you are only taking an opioid on an intermittent basis during the day and you take the LDN at night.

“One of two things may happen,” says Mackey. “Patients may not notice any difference in the opioid’s effectiveness, or they may experience a reduced benefit of the opioid due to the LDN.” If you are on an opioid, Aitcheson adds, “Expect more gastrointestinal side effects for the first few weeks of LDN.”

Whether you take an opioid on bad days or are on tramadol (a weak opioid), Fishman still recommends LDN. However, his standard dosing schedule is to start at 1 mg and increase 0.5 mg per week until 4.5 mg/day is reached. If a person is on an around-the-clock opioid, very low-dose naltrexone (0.5 mg or less) may be used as the starting point.

“In this era of the opioid epidemic where opioids were prescribed when all else failed for chronic pain,” says Fishman, “we need to consider positioning alternative strategies early on, including LDN.”⁴

Compounding Pharmacies

LDN must be compounded as an immediate-release, short-acting formula. If you take LDN for your fibromyalgia at bedtime, it is out of your system by morning.

Whether you use a local compounding pharmacy or a mail-order company, make sure it is PCAB accredited. This means the pharmacy meets the Pharmacy Compounding Accreditation Board standards set forth in the United States. If you live outside the US, be sure your pharmacy meets the highest standards set forth by your country.

Naltrexone is dirt cheap. The cost of LDN has to do with the labor involved in making the capsules or tablets. Typically, local compounding pharmacy only offer LDN in capsule form, while a few mail-order companies dispense scored tablets.

“The price range is substantial,” says McKenzie-Brown. “When I found a pharmacy that compounded scored tablets, it substantially reduced cost.” She uses one-half tablets during the titration phase, then she switches patients to the more economical 90-day supply.

While going through a dosing up phase minimizes concerns about side effects, there are two disadvantages: increased cost and the inconvenience of requiring a second script for the target dose (usually 4.5 mg).

If you don’t want to hassle with mail-order pharmacies (or they are not available in your country), expect to pay about $1/capsule. Shop around though, because some places will charge you double.

Getting LDN for Fibro

How does your doctor write the scripts for dosing up and testing LDN? Whether you work with a local or a mail-order compounding pharmacy, the information you need to know is below.

Local Pharmacies

If your local compounding pharmacy dispenses LDN capsules at a reasonable price, use them for the first three months. You can switch to a mail-order pharmacy if LDN provides symptom relief.

If you want to dose up, rather than start out at 4.5 mg at bedtime, you will need two scripts (get both from your doctor in the same visit). Assuming you start at 1.5 mg per day, your physician will need to write the following two scripts:

Script #1
1.5 mg capsules of immediate-release naltrexone – quantity 21
Instructions: take one capsule at bedtime for the first week, then take two capsules at bedtime for the second week.

Script #2
4.5 mg capsules of immediate-release naltrexone – quantity 90
Instructions: take one capsule at bedtime

NOTE: If you are drug-sensitive, ask your physician to change the dosing schedule for Script #1 to two weeks and increase the quantity to 42. Just keep in mind that Script #1 is an added expense to your LDN trial period.

If you want to just give 4.5 mg per day a try, you only need the second script above. However, you may ask your doctor to write Script #1, but not fill it unless you encounter side effects that can’t be managed.

Mail-Order Pharmacies
For Scored LDN Tablets

Care First Specialty Pharmacy in Mount Laurel, NJ provides scored LDN tablets in doses ranging from 0.5 mg to 6 mg. They are approved to ship to all 50 states plus the Virgin Islands, and their prices are excellent at $0.57/tablet. However, Avrio Pharmacy of Scottsdale, AZ offers a unique product: double-scored LDN “Quad” tablets. This means that you can dose up on 4.5 mg tablets and conveniently stay with the same script for the long run. Unfortunately, Avrio is not licensed to ship to 12 states.

Care First Specialty Pharmacy
www.cfspharmacy.pharmacy
TEL: (844) 822-7379
FAX: (844) 922-7379
Standard Shipping: $3.95; Cost for 90 scored tablets:
Any strength 0.5 mg – 4.5 mg is $46.95
5 mg is $48.95
6 mg is $59.95

Anything above 6 mg must be made into capsules; expect to pay closer to $80.

Dosing up in 1.5 mg increments requires 3 mg tablets; 135 costs $67.50
Patients on around-the-clock opioids may talk to their doctor about taking the 0.5 mg strength (each half tablet is only 0.25 mg). Care First also makes available “ultra” low dose naltrexone in micro-milligrams (mcg).

Patient registration forms, as well as prescriber forms, are available on their website. Or call to set up your profile for shipping address and payment info.

Avrio Pharmacy
avriorx.com
TEL: (480) 270-6700
FAX: (480) 270-6701
Standard Shipping: $8; Cost for 90 Quad tablets:
4.5 mg (1.125 mg segments) is $60.00
2 mg (0.5 mg segments) is $60.00
6 mg (1.5 mg segments) is $75.00

If you want the safety net of dropping the dose for a few days without needing a second script, the 4.5 mg quad tablets are ideal. Just keep in mind that Avrio does not ship to the following states: AL, AR, IA, LA, MD, MS, NJ, ND, OK, TN, VT, WV.

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References