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Where Fibromyalgia and Chronic Fatigue Syndrome Part Ways (and Where They Don’t)

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Reprinted with the kind permission of Cort Johnson and Health Rising.

Lately we’ve seen what appears to be a great deal of similarity in muscle issues in Chronic Fatigue Syndrome and Fibromyalgia. We know that Dr. Bateman and others believe ME/CFS and Fibromyalgia occur on a fatigue-pain continuum – that they are similar disorders that differ in the amount of fatigue and pain present. They both predominantly affect women, and similar medications are used in both.

Both Dr. Natelson and the Lights, however, have found differences in ME/CFS + FM vs ME/CFS patients alone, and Natelson argues that they’re quite different disorders.

Now a recent study demonstrates an important way that this is so.

Reduced levels of BDNF – described as a nerve repair agent – were recently found in Chronic Fatigue Syndrome and multiple sclerosis. The levels found – less 25% of normal – were stunningly low, and this suggested that neuron functioning was taking a real hit in both these disorders. Given the nerve damage found in MS, that result was expected for MS – but not in ME/CFS.

A recent Fibromyalgia BDNF study seems to portray a very different disorder. It examined BDNF and a marker of central sensitization (S100B) in the blood of fifty-six FM patients and then determined if this correlated with pain pressure thresholds (the threshold at which pressure starts producing pain). The lower the pain threshold, the more pain a person is in. The study did not involve healthy controls and thus did not, strictly speaking, determine if BDNF levels were higher or lower than normal in FM.

Microglia Activation and Central Sensitization

Before we get to the findings, let’s look at S100B. S100B is such an intriguing factor that it’s surprising it hasn’t been studied before in FM or in any other pain disorders. S100B upregulates two key cytokines, IL-1b and TNF-a, both of which may be involved in FM and ME/CFS. It also activates the nuclear transcription factor which Maes proposes underlies the inflammatory milieu in ME/CFS and depression. It is also considered a surrogate for microglial activation.

Study Findings

This study found that increased BDNF and S100B levels were associated with increased pain sensitivity in FM. Other studies have found increased BDNF levels in FM as well. These FM findings contrast sharply with the decreased BDNF levels found in ME/CFS.

With regards to BDNF, ME/CFS looks more like multiple sclerosis than it does Fibromyalgia.

High Levels of Excitation vs Low Levels of Nerve Repair?

While high levels of BDNF in FM look like they’re enhancing the activity of excitatory pain pathways in FM, low levels of BDNF in ME/CFS look like they may be impeding neuron repair and slowing down nerve transmission. Could FM be a disorder of brain excitation while ME/CFS is a disorder of brain loss and slowed functioning? Could it be that simple?

A quick look at the research findings in ME/CFS and Fibromyalgia indicate more overlaps than dissimilarities. Both are characterized by sympathetic nervous system activation, reduced aerobic capacity, increased lactate levels (in one place or another), reduced brain blood flow, decreased cortisol, and decreased grey matter in the brainstem.

Similarities between the ME/CFS and Fibromyalgia

Differences between the ME/CFS and Fibromyalgia

Central Sensitization – the Key?

It’s intriguing that the two major differences between the two disorders, increased substance P and BDNF in FM, are associated with central nervous system activation.

Given the high amount of pain and problems with stimulus overload, we’ve assumed ME/CFS is also a central sensitization disorder. Yet two markers associated with central sensitization that are elevated in FM, BDNF and substance P, are not elevated–or are actually lowered–in ME/CFS.

The excitatory neurotransmitter glutamate is also clearly increased in some parts of FM patients’ brains, but a CDC gene expression study suggested decreased glutamate uptake may be present in ME/CFS. At the Stanford Symposium Dr. Zinn described an ME/CFS brain characterized by substantial ‘slowing’. It was a brain that seemed to be more asleep than awake.

On the other hand, Jason has proposed that limbic kindling produces a kind of ‘seizure activity’ in parts of the brain in ME/CFS, and high levels of neuropeptide Y and reduced heart rate variability indicate the sympathetic nervous system is activated in both disorders. Klonopin (clonazepam), a nervous system inhibitor, is used in treating both disorders.

In the end it may be that, like the immune system in ME/CFS, parts of the brain are over- and under-activated in both disorders.


Increased levels of BDNF and S100B levels are associated with increased pain sensitivity in Fibromyalgia. They join a variety of other markers of central sensitization markers found in FM.

Differing levels of BDNF and substance P in Chronic Fatigue Syndrome and Fibromyalgia suggest that the two disorders differ in important ways. However, the two disorders share many more commonalities than differences. The central nervous system could be, however, where the two disorders diverge.

Pain is common in ME/CFS, but it appears that the pain is, at least in part, being produced in different ways than it is in Fibromyalgia.


About the Author:  Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort’s and other bloggers’ work at Health Rising.

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6 thoughts on “Where Fibromyalgia and Chronic Fatigue Syndrome Part Ways (and Where They Don’t)”

  1. ProHealth-Editor says:

    We’re so glad you liked the article. You will have to ask the author, Cort Johnson, for permission to reprint his article. You can contact him through his website: http://www.cortjohnson.org/

    Karen Lee Richards
    FM Editor

    1. Bolton72 says:


    2. mushmel says:

      Im sure this article would be of great interest to me as a sufferer of Fibromyalgia if I could understand what it is saying! I have no medical knowledge so i need any articles to be in plain easy to understand terms.

  2. Reginafm says:

    Not really sure what to write-just reaching out for help and ideas. Recently diagnosed with fibromyalgia but don’t seem to have chronic fatigue syptoms (yet-do they come later?)
    Looking at all kinds of herbal remedies as the only thing that seems to work is anything in th valium family which is scary!
    Anyone find any great combo that they’d be willing to share-this thing has really rocked my world!!!

    1. Bolton72 says:

      This is a really interesting and informative article. Would our group be able to reprint it in our newsletter? We would give full credit, of course. We have many members who have been diagnosed with both conditions, and some who have either one or the other. We are also affliliated to both ME and fibromyalgia national groups.

      Bury and Bolton ME/CFS support group

    2. notthedisease says:

      Regina I hope you come back to read this. I’m new to the forum, but I was diagnosed with Fibromyalgia and ME/CFS 7 years ago.

      One very important thing is to get adequate sleep. I have to take a med for this, but there are nights when even that doesn’t work. I’ve found that relaxation apps (I use Andrew Johnson’s apps) assist in the sleep. That means a little less pain than I have after a sleepless night.

      As far as herbal remedies, talk with your rheumatologist about options. Herbal doesn’t always mean safe, and if you mix things that should not be mixed it could spell disaster.

      Something that you might want to try for the pain is either Unkers Salve or Tiger Balm. Both are similar to Vick’s medicated rub, with slightly different formulas. Unkers is made in the US and is a favorite for the Amish.

      The fatigue may or may not come. I had marked fatigue before I was diagnosed, but I know others who have not experienced the level of fatigue I have.

      It’s a rough illness to have, but the more you move the better you’ll feel. There will be days when you dread getting out of bed in the morning because the stiffness is so bad. There will be times when you are in what’s called a “flare,” when every tender point that affects you makes you feel as though you are on fire. I’ve found during flares resting is the only thing I can do. I do daily things like dishes and laundry, but other than that I become a slug until the flare subsides. Drastic weather changes and extreme weather conditions (sub-freezing temps and high heat and humidity) are classic causes of flares.

      I hope some of this information helps. Sending you soft gentle hugs.

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