Patients with fibromyalgia display less functional connectivity in the brain's pain inhibitory network

Abstract

Background: There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome (FM). In order to fully understand the mechanisms involved in FM pathology, there is a need for closer investigation of endogenous pain modulation. In the present study, we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC).We performed functional magnetic resonance imaging (fMRI) in 42 subjects; 14 healthy and 28 age-matched FM patients (2 patients per HC), during randomly presented, subjectively calibrated pressure pain stimuli. A seed-based functional connectivity analysis of brain activity was performed. The seed coordinates were based on the findings from our previous study, comparing the fMRI signal during calibrated pressure pain in FM and HC: the rostral anterior cingulate cortex (rACC) and thalamus.

Results: FM patients required significantly less pressure (kPa) to reach calibrated pain at 50 mm on a 0-100 visual analogue scale (p < .001, two-tailed). During fMRI scanning, the rACC displayed significantly higher connectivity to the amygdala, hippocampus, and brainstem in healthy controls, compared to FM patients. There were no regions where FM patients showed higher rACC connectivity. Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients.

Conclusion: Patients with FM displayed less connectivity within the brain's pain inhibitory network during calibrated pressure pain, compared to healthy controls. The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients. It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implications by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation.

Figure 1

Pressure needed to evoke the same subjective levels of pain in FM patients and controls. A total number of 15 thumb-pressures were given in order to calculate the pressure that would represent a pain intensity of 50 mm VAS (0–100). A two-samples t-test confirmed that patients required significantly less pressure (kPa) than controls in order to reach VAS 50 mm; p < .001, two-tailed.

Figure 2

Experimental pain paradigm and functional connectivity results. The schematic illustration (A) represents the experimental pressure pain paradigm used during fMRI scanning. Calibrated painful pressures (long lines), representing 50 mm VAS, and non-painful pressures (short lines) were randomly delivered to the thumbnail during 2 adjacent 8 minute runs with 20 painful and 10 non-painful stimuli in each run. Functional connectivity results for the rACC seed (B) revealed incraesed connectivity to the amygdala (peak coordinate x = −14, y = 0, = − 16) and a cluster encompassing the brainstem/PAG/hippocampus (peak coordinate x = 12, y = 24, z = −12) in healthy controls, comapred to FM patients. Functional connectivity results for the thalmaus seed (C) revealed increased connectivity to the OBFC (peak coordinate x = −34, y = 50, z = −18) in healthy controls, compared to FM patients. All anatomical locations are given in Montreal Neurological Institute coordinates (MNI).