Korean J Pain.  2023 Jan;36(1):113-127. 10.3344/kjp.22225.

Primary somatosensory cortex and periaqueductal gray functional connectivity as a marker of the dysfunction of the descending pain modulatory system in fibromyalgia

  • 1Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
  • 2Laboratory of Pain and Neuromodulation at Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
  • 3Department of Psychiatry, Faculdade de Medicina, UFRGS, Porto Alegre, Brazil
  • 4ADHD Outpatient Program, HCPA, Porto Alegre, Brazil
  • 5Department of Internal Medicine, UFRGS, Porto Alegre, Brazil
  • 6Laboratory of Pharmacology in Pain and Neuromodulation: Pre-clinical Investigations, Experimental Research Center, HCPA, Porto Alegre, Brazil
  • 7Pain and Palliative Care Service, HCPA, Porto Alegre, Brazil
  • 8Laboratory of Neuromodulation and Center for Clinical Research Learning, Physics and Rehabilitation Department, Spaulding Rehabilitation Hospital, Boston, MA, USA


Resting-state functional connectivity (rs-FC) may aid in understanding the link between painmodulating brain regions and the descending pain modulatory system (DPMS) in fibromyalgia (FM). This study investigated whether the differences in rs-FC of the primary somatosensory cortex in responders and non-responders to the conditioned pain modulation test (CPM-test) are related to pain, sleep quality, central sensitization, and the impact of FM on quality of life.
This cross-sectional study included 33 females with FM. rs-FC was assessed by functional magnetic resonance imaging. Change in the numerical pain scale during the CPM-test assessed the DPMS function. Subjects were classified either as non-responders (i.e., DPMS dysfunction, n = 13) or responders (n = 20) to CPM-test. A generalized linear model (GLM) and a receiver operating characteristic (ROC) curve analysis were performed to check the accuracy of the rs-FC to differentiate each group.
Non-responders showed a decreased rs-FC between the left somatosensory cortex (S1) and the periaqueductal gray (PAG) (P < 0.001). The GLM analysis revealed that the S1-PAG rs-FC in the left-brain hemisphere was positively correlated with a central sensitization symptom and negatively correlated with sleep quality and pain scores. ROC curve analysis showed that left S1-PAG rs-FC offers a sensitivity and specificity of 85% or higher (area under the curve, 0.78, 95% confidence interval, 0.63–0.94) to discriminate who does/does not respond to the CPM-test.
These results support using the rs-FC patterns in the left S1-PAG as a marker for predicting CPM-test response, which may aid in treatment individualization in FM patients.


Central Nervous System Sensitization; Chronic Pain; Fibromyalgia; Functional Neuroimaging; Magnetic Resonance Imaging; Neural Pathways; Pain Perception; Periaqueductal Gray; Psychophysics; Somatosensory Cortex


  • Fig. 1 Timeline assessments. VAS: visual analog scale, CPM: conditioned pain modulation, NPS: numerical pain scale, fMRI: functional magnetic resonance imaging.

  • Fig. 2 Visual representation of rs-FC ROI-to-ROI analysis according to connectome ring view: (A) p-uncorrected, (B) after p-FDR (analysis-level correction), and (C) along with the 3D map. The blue line indicates lower rs-FC between left S1 and PAG in non-responders than in responders. Maps were made using the CONN-fMRI Functional Connectivity toolbox [51]. P ≤ 0.001, FDR ≤ 0.05. rs-FC: resting-state functional connectivity, ROI: region of interest, FDR: false discovery rate, PAG: periaqueductal gray, fMRI: functional magnetic resonance imaging, L_: left, R_: right, S1: primary somatosensory cortex, S2: secondary somatosensory cortex, M1: primary motor cortex, DLPFC: dorsolateral prefrontal cortex, MPFC: ventromedial prefrontal cortex, aIC: anterior insular cortex, pIC: posterior insular cortex, ACC: anterior cingulate cortex, VLTh: ventrolateral thalamus, MDTh: mediodorsal thalamus, Hippo: hippocampus, Amyg: amygdalae, NA: nucleus accumbens, 3D: three dimensional.

  • Fig. 3 Nonparametric receiver operating characteristics analysis. The area under the curve (AUC) with exact binomial 95% confidence intervals of S1-PAG rs-FC. rs-FC: resting-state functional connectivity, S1: primary somatosensory cortex, PAG: periaqueductal gray.


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