Studies showing that the parts of the brain that process pain signals are lit up like Christmas trees in fibromyalgia, migraine, and other chronic pain disorders indicate that the brain plays a major role in these diseases. Other fibromyalgia studies, which indicate that the habituation mechanism which should automatically reduce pain over time isn’t working so well, also indicate brain involvement.

brain fibromyalgia

The brain is involved in FM – but is it the only major player?

Findings like these suggest that the central nervous system is the main culprit in fibromyalgia (FM).  Sympathetic nerves have also been implicated with recent findings showing small nerve fiber damage in the skin, eyes and perhaps elsewhere in a significant subset of FM patients. Why these nerve fibers are being damaged and/or disappearing is unclear, but some believe that a past or present immune disorder is the culprit.

Two different nerve fibers in the skin exist: one transmits pain signals and the other sympathetic nervous system signals. Since problems in both the pain response and sympathetic nervous system exist (and are likely intertwined) it’s possible that both types of nerve fibers have been damaged in FM.  Plus, since the sympathetic nervous system (SNS) or “fight or flight” response is immediately triggered by pain, its potential relevance to FM comes as no surprise. Some researchers such as Dr. Martinez-Lavin believe the pain sensitivity in fibromyalgia is directly triggered by aberrant sympathetic nervous system activity.

The big question right now is if the two findings – central nervous system problems and the skin nerve issues in fibromyalgia –  are connected.  That’s what the Italian researchers in the study below tried to find out.

The Study

Marina de TommasoKatia Ricci, 1 Giuseppe Libro, 1 Eleonora Vecchio, 1 Marianna Delussi, 1 Anna Montemurno, 1Giuseppe Lopalco, 2 and Florenzo Iannone 2. Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials. Pain Res Treat. 2017: 9747148.

In the present study, the Italian researchers attempted to cross the divide between body and brain by assessing two seemingly disparate processes in a single group of patients. A “laser-evoked potentials” (LEP) test was used to determine if the habituation process in the brain which should tamp down pain signals was working in FM.  The “sympathetic skin response”  test measured whether the sympathetic nerves in the skin were working  properly.

Study findings indicating that sympathetic skin response (SSR) is delayed in FM suggest that problems with these nerves in the skin may exist. One research group even proposes that SSR testing could provide the first biological test for FM. Their recent neural network study used the SSR test to very accurately determine (97.7%) who had FM and who didn’t.

The big question facing this study was whether problems with sympathetic nerves in the body would also be associated with central nervous system problems. A positive answer to that question would heighten the complexity of FM significantly, and cast doubt on the idea that the pain problems in FM arise solely from problems with the central nervous system.


The results revealed a heterogenous group of patients. The FM group as a whole exhibited both a slowed response of the sympathetic nervous system fibers in the skin and a blunted habituation process. The two results tied together brain and body suggesting that fibromyalgia is a disease not just of central sensitization, but which also tends to effect sympathetic nerves.

A third of patients who displayed no results at all on one of the LEP and SSR tests were clearly different. These patients, who turned out to be the most severely affected of all, reported high levels of neuropathic pain. The lack of an SSR response suggested that their sympathetic nervous system nerves may have been effectively trashed in some places. That fact that this same strange pattern – no results measured – also showed up in the LEP test suggested, as did the first part of the study, that something in common may be underlying both the SSR and LEP results.

In fact, a brain network (insular cortex, anterior cingulate cortex (ACC), prefrontal cortex (PFC), posterior parietal cortex (PPC), secondary somatosensory cortex (S2), thalamus, and midbrain) exists which regulates both pain and sympathetic nervous system functioning. Virtually all of these brain areas have been implicated at one time or the other in fibromyalgia.

Another finding, that the habituation pain response was more blunted in FM patients with increased anxiety, was not entirely surprising. Studies indicate that negative mental states such as catastrophizing increase pain sensitivity in FM and other chronic illnesses. (One study, however, found no correlation between anxiety and pain in fibromyalgia.)


The results opened up a nice can of worms. For possibly the first time, problems with peripheral nerves in the body were correlated with central nervous system issues in fibromyalgia. Correlation is not causality, but the finding suggested that an underlying problem – still unnamed – may be producing problems in both the sympathetic and central nervous systems in fibromyalgia.

This study suggests one problem could be underlying the central and peripheral nerve problems in fibromyalgia.

The authors pointed to a section of the brain which regulates both sympathetic and sensory stimuli processes as potentially a key factor. Immune processes are also potentially a key factor.

Plus, about a third of FM patients with more neuropathic pain and disability were different. These patients exhibited no results on one of the tests suggesting that significant nerve damage may be exacerbating or causing more pain in them.  The authors called for more studies of neuropathic pain in FM.

That small nerve fiber problems are present in FM is clear. The big question is why they’re present, what do they mean for the other issues in FM, and how to treat them? This study presents the preliminary but intriguing possibility that the issues in the brains and bodies of FM patients are connected.

Next, we’ll look at a potentially ground-breaking study which suggests that treating the small nerve fiber problems with an immune modulator may, in some FM patients, be very effective indeed.

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