Neurobiology underlying fibromyalgia symptoms.
Ceko M, Bushnell MC, Gracely RH.
Alan Edwards Centre for Research on Pain, McGill University, 3640
University Street, Room M19, Montreal, QC, H2A 1C1, Canada.
Fibromyalgia is characterized by chronic widespread pain, clinical
symptoms that include cognitive and sleep disturbances, and other
abnormalities such as increased sensitivity to painful stimuli,
increased sensitivity to multiple sensory modalities, and altered pain
Here we relate experimental findings of fibromyalgia symptoms to
anatomical and functional brain changes. Neuroimaging studies show
augmented sensory processing in pain-related areas, which, together
with gray matter decreases and neurochemical abnormalities in areas
related to pain modulation, supports the psychophysical evidence of
altered pain perception and inhibition.
Gray matter decreases in areas related to emotional decision making
and working memory suggest that cognitive disturbances could be
related to brain alterations.
Altered levels of neurotransmitters involved in sleep regulation link
disordered sleep to neurochemical abnormalities.
Thus, current evidence supports the view that at least some fibromyalgia symptoms are associated with brain dysfunctions or
alterations, giving the long-held "it is all in your head" view of the disorder a new meaning.
What Do the Psychophysical, Cognitive, and Neuroimaging Studies Tell
Us about the Neurobiology Underlying FM Symptoms?
The wealth of experimental evidence showing that FM patients are
hypersensitive to painful stimuli, as well as unpleasant stimuli from
other sensory modalities, in conjunction with functional brain imaging
data showing increased stimulus-evoked activation throughout
nociceptive pathways, shows that the defining symptom of FM—increased
pain—is in fact real and not just a response bias of the patients. The
finding that perception is increased in multiple modalities speaks
against the hypothesis that FM pain is due to an upregulation of
peripheral nociceptive processes. Further, psychophysical evidence
that descending modulatory systems are altered in FM patients supports
the opposing idea that FM symptoms are at least in part caused by
alterations in CNS processing of the pain signal, including a
dysregulation of pain modulatory systems. Nevertheless, the apparent
dysregulation within these systems could be caused and/or perpetuated
by a tonic activation related to the presence of ongoing widespread
pain, so that the systems are saturated and cannot regulate further in
response to external stimuli.
Since similar descending control systems, including attentional and
emotional regulatory circuitry, affect multiple sensory modalities
[113–119], a dysfunction (or saturation) in these systems could lead
to the hypersensitivity in multiple sensory modalities. FM patients
show reduced habituation to nonpainful tactile stimuli and increased
cortical response to intense auditory stimuli, both of which have been
linked to deficient inhibition of incoming sensory stimuli [120, 121].
Also in support of the idea of a central dysregulation or saturation
of pain modulation are changes in the opioid and dopamine
neurotransmitter systems, both known to be involved in hedonic
Finally, the findings that FM patients not only perceive themselves to
have altered memory and concentration ("fibrofog"), but also in fact
perform poorly on multiple cognitive tests, even when depression is
excluded as a contributing factor, suggest that there are alterations
in brain function. The anatomical brain imaging studies that show
reductions in gray matter in frontal regions important for cognitive
function further indicate that this common symptom of FM is based on
altered brain function. Together, the experimental evidence provides
strong support for the idea that FM symptoms are related to
dysfunctions in the central nervous system. The cause of these changes
cannot be deduced from the available evidence, as it is correlational
in nature. Did long-term ongoing pain cause the changes or did the
changes cause the pain? Without a relevant animal model or long-term
longitudinal studies, we cannot answer these questions.
Nevertheless, we can at least say that fibromyalgia is real and that it is associated with multiple changes in the brain.
PMID: 22135739 [PubMed - in process]
The full study can be found here: