Sometimes you don’t know if you should laugh or cry. This study starts off with a list of abnormal findings in fibromyalgia: there’s the central nervous system sensitization which involves increased activity in the brain’s pain processing regions, increased responsiveness in regions that that process ‘noxious stimuli’, and there’s an inability to become habituated to painful stimuli (the pain should diminish over time – not get worse!).

J Neurol. 2013 Dec 24. Update on laser-evoked potential findings in fibromyalgia patients in light of clinical and skin biopsy features. de Tommaso MNolano MIannone FVecchio ERicci KLorenzo MDelussi MGirolamo FLavolpe VProvitera VStancanelli ALapadula GLivrea P.
question marks

Despite all that is known about fibromyalgia many questions remain.

But then, the authors say, we really don’t have any idea what’s causing fibromyalgia! In fact, researchers know several of the things that have gone wrong in fibromyalgia, but they don’t know what’s causing them to go wrong. This study could bring us closer to what’s causing things to go wrong.

A recent study suggested that pain processing centers of the brain in young people protect themselves from a kind of pain signal ‘assault’ by ‘bulking up’ (increasing grey matter) and decoupling themselves from each other. Both these attempts get reversed in older patients leaving one more hypersensitive to pain.

This pain signal assault could be generated in three places in the body that I know of, and probably more: at the dorsal horn of the spinal cord (which filters signals to the brain), at the sensory ganglia, or in the sensory nerves. The study examined the sensory nerve network emanating from the skin to see if it was damaged and was sending unusual signals to the brain.

The Study

Researchers commonly stimulate the nervous system to see how it responds. In this study, laser-evoked potential (LEP) tests specifically targeted the small nerve fibers that carry the messages from the skin to the spinal cord . As the laser heated up the skin the researchers examined the electrical charge in the small nerve fibers to determine if they were functioning properly.


Researchers measured the nervous system response to laser induced pinpricks of pain in the skin

Because the small nerve fibers carry pain signals, they could be involved producing the neuropathic (nerve) pain present in fibromyalgia and chronic fatigue syndrome. Until recently, however, studies assessing small nerve fiber neuropathy in fibromyalgia and chronic pain disorders have been rare. Now some small studies suggest rates of small fiber neuropathy (SFN) in FM could be quite high.

This was a big study. Laser evoked potentials were done three times each in three different places in 199 patients as well as 109 age- and sex-matched controls. Skin biopsies to assess small fiber density were taken in three places each in 20 patients and 60 controls.

As a laser evoked pinprick and burning sensations at three tender points, the researchers measured the laser-evoked potentials produced and asked the participants to assess the amount of pain they experienced. The corresponding amplitude and habituation of the electrical response was measured.

The Findings

Nervous System Activity

The laser pinpricks evoked, not increased, but reduced electrical responses ( e.g. amplitude) from the sensory nerves in most FM patients relative to the controls. The reduced strength of the electrical signals resulting from stimulation by the laser indicated problems with the nerves were present.

People with migraine and FM tended, on the other hand, to have normal or increased response. This suggested that a very different subset was embedded in the larger fibromyalgia population.


“The tendency not to habituate across consecutive sessions of painful stimulation seems to be a stable pattern in fibromyalgia, which is not influenced by psychological factors and is correlated to illness severity” Authors

The nervous system should quickly become habituated to and respond less vigorously to the laser pricks over time; indeed, the strength of the electrical signal (the evoked potential) dropped by almost 50% by the third pinprick in the healthy controls, but by only about 15% in the FM patients.

woman in pain

The pain inhibition didn’t fully kick in in many FM patient, and in some FM patients with migraine, the pain system got more responsive – not less

This suggested that FM patients’ nervous systems were inordinately provoked by the initial pain signals and had trouble turning them off. This kind of continuing arousal can be seen in a number of instances in FM and ME/CFS: in contracting muscles that never completely relax in FM, in a heart rate that does not calm down during rest, and in a sympathetic nervous system activation that doesn’t stop in both disorders.

One might also include the flu that never ends for many chronic fatigue syndrome patients. In both disorders an event (infection, trauma) triggers a response (sickness behavior and/or pain) that should get ameliorated over time, but the return response, which should swing the system back to homeostasis, doesn’t kick in.

In this case that the anti-nociceptive or anti-pain pathways descending from the brain were not kicking in to ameliorate the pain present in fibromyalgia.

Migraine and Fibromyalgia Subset

That was bad enough, but a subset of patients with FM and migraine (40% of the group) probably had the worst of it. By the third pinprick their nervous system response had not only not habituated, but had significantly increased indicating that their pain response system was revving up when it should have been revving down.

migraine aura

The researchers appeared to suggest that the central sensitization in migraine was so strong that it could produce fibromyalgia all by itself.

Migraine is becoming an ever more interesting aspect of both FM and ME/CFS. Rates of migraine appear to be quite high in both disorders, and it will no doubt be taken more into account in future studies. The authors suggested that the increased central sensitization in migraine this study showed was present could cause fibromyalgia to occur without any increase in pain signals from the body at all; i.e., the migraines are setting the foundation for FM to more easily occur.

This inability to reduce the central nervous system response to pain signals turned out to be important, as it was associated more than any other finding with reduced quality of life and increased pain levels at the FM tender points.

Small Fiber Neuropathy Found

“Our present opinion, which needs further confirmation by the enlargement of the skin biopsy data, is that idiopathic peripheral sensory nerve involvement may be part of FM syndrome.” Authors

Small nerve fiber neuropathy (reduced nerve fiber density) was present in 90% of the 21 patients tested. The authors noted that it was different from the kind of SFN than usually seen. This finding buttressed the finding of a recent study that also found reduced electrical signal responses in FM patients and which postulated that SFN was present.

frayed wire

The researchers suggested the same factors that reduced nerve density in the skin caused the central sensitization in the brain.

Recent studies suggest a strong genetic component is present in both fibromyalgia and chronic fatigue syndrome, and SFN may be heritable as well. A gene mutation causing hyperexcitability in the dorsal root ganglion neurons that process the pain signals is associated with severe neuropathic pain. (A mutation that reduces dorsal ganglia excitability is associated with indifference to pain.)

This study found considerable evidence of small fiber neuropathy, but the findings suggested that the lack of habituation by the central nervous system played more of a role in producing pain than the nerve fiber problems leading from the skin to the spinal cord. (That finding, however, was based on a small sample size.)

The authors suggested, however, that the small nerve fiber problems they found in the skin probably extended to the nerve fibers associated with the muscles and joints, and that ion channel dysregulation probably caused both the small fiber problems and the neuron problems associated with central sensitization. (A sodium channel polymorphism has been associated severe fibromyalgia. )

In short, they believe the same general problem is causing the small nerve fiber problems in the skin, muscles. and joints, as well as neuron problems in the brain and spinal cord.



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