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Small Fiber Neuropathy Fibromyalgia Study Raises Questions

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

At least five studies have found significantly increased rates of small fiber neuropathy (SFN) in the skin of people with Fibromyalgia. SFN refers to the damage or destruction of the small unmyelinated sensory and/or autonomic nerve fibers. It’s believed that damage to these nerve fibers may cause symptoms such as tingling, burning sensations and pain.

Exactly how this happens isn’t clear, however, since the loss of these nerve fibers should result in the loss of sensation. One study which found that the remaining nerve fibers were in a hyper-excitable state could help explain how SFN could contribute to the pain found in FM. That still doesn’t explain, though, why the remaining small nerve fibers are in a hyper-excitable state to begin with.

A German team that had found evidence of small fiber neuropathy in FM last year thought they had the answer. They hypothesized that increased levels of pro-inflammatory cytokines were sending those remaining nerves bananas and they had good reason to think so. An earlier study of theirs found increased cytokine expression in the skin of people with SFN (who didn’t have Fibromyalgia), and a study by another group found increased gene expression of cytokines and vastly increased expression of opioid receptors in the skin of people with Fibromyalgia.

All that was needed now was a validation study and researchers could start targeting pro-inflammatory cytokines. It wouldn’t explain why the SFN was present (although pro-inflammatory cytokines could play a role) – but it could help explain why it was causing symptoms in Fibromyalgia.

The Study

Using very sensitive techniques, they compared gene expression of pro- and anti-inflammatory cytokines and opioid receptors in the skin of 25 people with FM, 10 people with major depression and 35 healthy controls.

In a surprise finding neither the gene expression of the cytokine or the opioid receptors were increased in the FM patients relative to the other groups.

With that finding researchers are back to square one in their efforts to translate the nerve damage seen in some Fibromyalgia patients to the pain they’re experiencing. Other possibilities include increased levels of immune factors called chemokines and problems with the ion channels in the remaining nerves.

The extent of small fiber neuropathy present was measured in the FM group, and as with the past studies, a subset of patients with SFN were found. The authors did not, however, state what percentage of FM patients had SFN. They did note, though, that cytokine gene expression of was not increased in this group.

Because chemokines essentially do the same thing as pro-inflammatory cytokines do – they provoke cells to respond – high levels of chemokines could play a role.

Ion Channelopathy A Possibility

Ion channel damage is another very real possibility. Ion channels play a key role in nerve signaling and ion channel alterations have been implicated in Fibromyalgia. Dr. Martinez-Lavin’s 2012 study found that Mexican women with severe FM tended to have a particular SCN9A sodium channel gene variant and a recent review fingered sodium channel problems in several types of painful SFN. Another recent review urgently urged more research into sodium channelopathies and peripheral neuropathy and asserted that research will reveal specific subsets of sodium channelopathy patients.

Researchers have gone so far as to identify a specific ion channel (Na(v)1.7) in the dorsal root ganglia that is disturbed in several pain syndromes. Genetic mutations in this channel allow ion channels to become activated in response to weaker stimuli, or to remain open longer in response to stimulation. That, of course, is a recipe for “central sensitization”: a hyperactive-response to sensory stimuli.

Deeper Nerve Fiber Loss Found

“Small fiber neuropathies are often associated with myovascular denervation”. Dori et. al

Finally, another recent study found that in addition to small nerve fiber denervation many patients also have nerve fiber loss associated with the blood vessels. Intriguingly, some people without small nerve fiber loss in the skin , demonstrated nerve fiber loss in the myovascular region. These patients had more muscle discomfort and autonomic nervous system problems.

One of the researchers in the initial round of SFN FM studies suggested that the nerve loss in skin may extend into deeper regions. This study did not involve FM patients but suggests it may indeed, and that some FM patients without evidence of SFN in the skin could have it in other regions.

Researchers Jump on SFN Findings

While the results of this study – and it was a small one – were disappointing note how quickly researchers have jumped on the small nerve fiber findings in FM. Not only have six studies over the course of a year or so been done, but researchers are already trying to understand how they are affecting FM patients with this problem.

Testing Lab Ramps Up SFN Testing Protocols

One indication that SFN has been generating more interest is Therapath Labs’ recent announcement that they’ve validated two more testing location on the body (between shoulder and elbow and above the wrist). Prior to this only three spots on the body, all on the legs, met the requirements for testing because it was unclear what constituted an abnormal result. That means more thorough testing for SFN is now available.

Expect to be hearing much more on the SFN problem in Fibromyalgia over the next year.


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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5 thoughts on “Small Fiber Neuropathy Fibromyalgia Study Raises Questions”

  1. pearls says:

    I wonder if this might have something to do with the temperature problems I experience in my kneecaps and hips? At night, I feel like those places are very cold, even if the rest of me is hot. However, if I feel the skin of my kneecaps or hips, neither place feels cold to my fingers. It is helpful, though difficult, to keep those places covered more than the rest of me, and this situation often interferes with my sleep.

  2. mother3000 says:

    I had Guillain-Barre Syndrome when I was 21 years old (1975). While recovering I had the exact feelings you describe as SFN… very painful. They gradually subsided. 15 years later I was diagnosed with CFIDS which has been changed by a Doctor to FM. Then approx. 20 years after that I was diagnosed with hypothroidism, my first TSH reading was 250 which is extremely high. A Doctor told me that immune diseases often clump together. The symptoms seem to overlap. I wonder if I am really suffering from a post-GBS syndrome. No studies have been done on the very long term effects of GBS. Have others had GBS before getting CFIDS or FM?

  3. jenn68 says:

    I appreciate that studies are being done to identify the underlying issues involved in many symptoms we experience. It is disappointing that the results were not more conclusive, but I wonder how a person can be tested for the SFN issue and what treatments might be available for this condition that differ from current treatments in FM. While managing symptoms is primarily what we can do at this point, I would really like to know how to address the underlying causes, so that a cure or at least true management of the condition could be accomplished. I know that studies like this one are steps toward that goal–it is just hard to wait when life is going by without any improvement. I’ve been suffering with this for well over twenty years, and while it is better with the treatments that are available today, it is also discouraging that we are not further along in treatments and diagnosis. But thank you ProHealth and all the researchers who are working toward that goal.

  4. ColleenD says:

    My feet and toes all around have been “half numb” and hypersensitive to most types of shoes, and walking for as long as I have had fibromyalgia (20 yrs). The only comfort I thankfully receive is wearing compression hosiery from the moment I awake in the morning to help me wear comfortable shoes. I look forward to understanding more about this symptom. Thank you, ProHealth, for this article!

  5. Dollyonline says:

    It seems when you are listening to the reports of monies going to research most of it is all going to Cancer. Although I feel Cancer is a worthwhile disease to put your money towards as far as research goes, I also feel there are thousands of us who could use an uplifting reminder that we too are important and that someone is trying to find the cause of our painful lifetime affliction and for them to do that, they too need financing.I believe that far too little is being done to investigate and research the causes and treatments that work for people with Fibromyalgia and Chronic Fatigue. I believe that because people aren’t dying of Fibromyalgia, it doesn’t rate the importance that Cancer does. We are put on the back burner in comparison to diseases like Cancer and heart problems. We too have rights and feel that we count and shouldn’t have to take a back seat.

    For me it has been over 30 years of physical pain along with mental anguish due to doctors telling me it was all in my head and family members thinking the same. They really had me believing I was losing my mind, until I finally insisted that I be sent to a specialist in Edmonton. Thanks to him, I finally had a good cry because I was told ‘no, it isn’t all in your mind…. you have Fibromyalgia and it shows in over 13 of 18 points on your body. I still had a long way to go to feel comfortable with the various doctors I went through to find one that was there for me. There are so many physicians out there that still tell people it is all in their heads.

    I feel that all doctors need to return to some form of education to learn about the new findings to do with Fibromyalgia and until they do, they should resist telling people that it is all in their heads. They also should do research on their own so that they can help their patients with as much info as possible both in natural medicine and prescribed medicines. Somewhere there is an answer and it can’t come soon enough for the millions of people who suffer from Fibromyalgia…. and Chronic Fatigue.

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