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An intriguing study done in the University of Würzburg and published in Brain march 9, 2013 indicates fibromyalgia pain is due to small fiber neuropathy. There has been the suggestion of nerve dysfunction in the past but this would demonstrate nerve damage. At one time fibromyalgia pain was thought to be in the muscles but there was no damage to the muscles to be seen so research moved up to the brain and there was plenty up there to be seen. While this was a generally small study it has impacted further research in this direction and brought more of an understanding about fibromyalgia as a syndrome.

The Study: Small fibre pathology in patients with fibromyalgia syndrome Brain first published online March 9, 2013

Twenty five fibromyalgia patients were involved in this study and “underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh.” (Study) The results were then compared with ten patients with depression and with healthy controls matched with age and gender.

Patients with fibromyalgia had higher scores in neuropathic pain questionnaires.

Patients with fibromyalgia had impaired small fiber function “with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001)” which essentially leads to increased temperature sensitivity.

There was indications of sensory dysfunction with fibromyalgia patients in the feet, face and hands: “Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents” (Study)

With fibromyalgia there was a lower amount of nerve fibers in total and less regenerating nerve fibers found in the skin: “In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects.” (study)

– Finally with the fibromyalgia patientsa reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared.” (Study)

The study concludes, “All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.”


Information on small fiber neuropathy

Your nerves are composed of cells call neurons connected by fibers called axons. The axons or fibers found in the skin, organs and other peripheral nerves are referred to as C fibers or small fibers. The fibers provide information such as pain and temperature sensations from the skin as well as maintaining automatic functions such as regulating heart rate, breathing and body temperature. Damage to the nerves themselves is called peripheral neuropathy and this can sometimes be a comorbid condition with fibromyalgia. Now within those fibers are a bundle of smaller strands bundled together with a casing. Some of the smaller bundles have a protective a casing called a myelin sheath and are called ‘myelinated’ while others do not and are refered to as ‘unmylinated’. It is the unmylinated bundles that appear to be damaged with fibromayglia and indeed according to the Pain Management and Rehabilitation Center in Chicago it is also the case for small fiber neuropathy itself.

The symptoms of small fiber neuropathy are “numbness, and annoying or painful sensations, called paresthesias, that are variably described as tingling, stinging, burning, freezing, itching, aching, pulling, squeezing, or electric shock-like. Innocuous stimuli can provoke unpleasant sensations, called dysesthesias; Clothes can feel like sandpaper against the skin, the hands may become hypersensitive to touch, or pressure from shoes or socks can causes severe pain in the feet. Symptoms of small fiber neuropathy can occur anywhere in the body, including the arms, legs, torso, face, or even the mouth.” (painrehabcenter) These sorts of symptoms are familiar to fibromyalgia and would account for fibromaylgia pain moving around the body. Lyrica and Cymbalta can be used to treat small fiber neuropathy which can account for why some people see a positive result with those medications.

Other known causes can be:

  • diabetes mellitus or glucose intolerance .
  • Sjogren’s syndrome
  • lupus
  • sarcoid
  • vasculitis
  • inflammatory bowel disease
  • Guillain-Barre syndrome variant
  • nutritional deficiencies
  • celiac disease
  • Lyme disease
  • HIV-1 infection
  • hereditary conditions including Fabry disease
  • amyloid
  • alcohol abuse or toxins .
  • Or unknown cause: idiopathic.

In conclusion

Nerve dysfunction is not unknown to fibromyalgia. Thermal allodynia is a common symptom whereby people with fibromyalgia will experience sharp, burning or tinging pain from heat or cold hypersensitivity. Allodynia by itself occurs as well where the scalp or other areas can become extremely sensitive for certain durations. Now perhaps it is not this at all. Perhaps it small fiber neuropathy and that is why this study is particularly interesting. We know that medications such as Lyrica and Cymbalta are used to treat the condition and also benefit some people with fibromyalgia which suggests neuropathy could be a could explanation for the pain. The question would be what is causing the damage. Certainly a good avenue for future research.

Rat study 2017
Reduced intraepidermal nerve fiber density after a sustained increase in insular glutamate: a proof-of-concept study examining the pathogenesis of small fiber pathology in fibromyalgia

Here is what the study states: “Neuroimaging reveals increased glutamate within the insula of patients with fibromyalgia (FM), suggesting a link between FM symptoms and increased central excitatory neurotransmission. Many patients with FM also present with decreased intraepidermal nerve fiber density (IENFD), consistent with small fiber pathology. It remains unknown, however, whether either of these mechanistic findings represent a cause or a consequence of the other. This study tests the hypothesis that an excitatory imbalance within the insula leads to small fiber pathology.” (Abstract)

The study is looking at whether the glutamate within our insula in fact leads to their findings of small-fiber neuropathy in people with fibromyalgia. They delivered an increase of glutamate into rats for 6 weeks into the insula. Then tissue biopsies were tested and assessed after the experiment.

Conclusion: “Bilateral insular PDC administration produced a persistent increase in multimodal pain behaviors and a decrease in peripheral nerve fibers in rat. These preclinical findings offer preliminary support that insular hyperactivity may be a casual factor in the development of small fiber pathology in FM.” (Abstract)

This particular study is looking for a cause to the small-fiber neuropathy that other studies have noted (see further reading).

Further reading:

Reduction of Intraepidermal Nerve Fiber Density (IENFD) in the skin biopsies of patients with fibromyalgia: A controlled study
Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy
Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia

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