A 2018 study 1 of resting state functional magnetic resonance imaging (rs-fMRI) of the cervical spinal cord in fibromyalgia patients and control subjects found there was greater ventral and lesser dorsal Mean ALFF of the cervical spinal cord in patients with fibromyalgia, compared to the control group subjects. The results of the study may indicate that fibromyalgia patients experience enhanced sensitization of nerve responses that could be responsible, in part, for the discomfort and fatigue associated with the disorder.
What’s at Stake
Patients with fibromyalgia report the experience of physical pain throughout the body, as well as cognitive problems, fatigue, anxiety, and depression. The symptoms may be a result of irregularity of the central nervous system (CNS), including central sensitization and possibly a decreased ability to modulate pain responses. Signals to and from pain receptors may be misdirected or skewed in patients with fibromyalgia, creating an altered response to nociceptive and non-nociceptive signals.
Previous imaging studies have demonstrated altered CNS activity or structure and irregular brain activity in response to painful and non-painful stimuli in fibromyalgia patients. Functional connectivity, networks, and low frequency oscillatory power have been measured through resting state functional magnetic resonance imaging (rs-fMRI), but these studies did little to elucidate the underlying CNS processes that occur in patients with fibromyalgia. Because of the complexity of the CNS signals in the spine, it was necessary to conduct a comparative rs-MRI of healthy controls and fibromyalgia patients to observe alterations of oscillatory frequencies, functional CNS connectivity, and analyze the graph metrics of the fibromyalgia patients.
The study subjects included 16 fibromyalgia patients whose symptoms met the American College of Rheumatology inclusion criteria for fibromyalgia and 17 healthy participants. Subjects with MRI contraindications, taking opioids for pain or mood-altering medications, and those with depression or anxiety disorder were excluded, as were pregnant or nursing females. All subjects were screened for MRI contraindications and filled out questionnaires regarding their psychological and behavioral state, diagnostic pain, sensory, and fatigue criteria prior to the study. Further testing assessed the subjects’ sensory, pain, cold pressure response, mechanical hyperalgesia, and mechanical temporal responses.
Each of the subjects was queried regarding their levels of pain prior to, and after their fMRI scans, using a scale of 0 to 10 to grade their pain. Separate amplitude of low frequency fluctuations (ALFF) Measures of Mean were calculated for each study subject across all voxels of the cervical spine data. Normalized images were analyzed for differences, and the significance of the findings was assessed. Gray and white matter Mean ALFF was also analyzed and compared in the study groups. The functional organization and connectivity of spinal cord networks was also observed and compared in both study groups, as other studies have suggested that bilateral motor, sensory, and dorsal horn functional connectivity networks was altered during thermal stimulation in humans and after a spinal cord injury in non-human primates. The researchers in this study wanted to investigate if disrupted spinal cord processing and functional organization may be responsible for some symptoms of fibromyalgia.
Results & Conclusions
The fibromyalgia patients had higher measures of fatigue, sensory hypersensitivity, and widespread pain than the control group. Each of the fibromyalgia patients had right shoulder pain, and most experienced arm pain, undermining the research expectation that the patients’ sensitization would be central and found throughout the CNS as a result of their altered cervical spinal cord activity.
The ALFF spinal cord low frequency oscillatory power study indicated a greater Mean ALFF in the ventral hemi-cord of the fibromyalgia patients. The dorsal quadrants of fibromyalgia patients showed lesser Mean ALFF. Mean ALFF was higher in gray matter than in white matter in the patients.
Overall, the study demonstrated that the cervical spinal cord of the fibromyalgia patients had altered patterns of rs-fMRI low frequency power—greater regional Mean ALFF in the ventral, and lesser in the dorsal spinal cord. The most pronounced difference was noted inside a small cluster in the right dorsal quadrant, at the border between the dorsal horn gray and white matter. There was a strong correlation between levels of patient fatigue reported and the noted differences in Mean ALFF. These observations support the idea of regional differences in nociceptive and non-nociceptive CNS processing pathways in patients with fibromyalgia.
While there is a need for future study of local spinal cord modulatory circuits, these findings suggest that a combination of reduced CNS inhibition, coupled with an increase in dorsal horn excitation could be responsible for the irregular modulation of sensory and pain signals experienced by patients with fibromyalgia. Nociceptive signals might be over-transmitted by spinothalmic projection neurons, and/or a similar process could cause the under-transmission of non-nociceptive signals. Irregular spinal cord signal modulations (decreased, or increased) could increase or lessen signals of any type to any part of the body, which might explain the experience of uncomfortable hot or cold sensations in patients with fibromyalgia. There was also a very strong correlation between the Mean ALFF of the fibromyalgia patients and their fatigue symptom measures.