pISSN 2005-9159
eISSN 2093-0569

Clinical Research Article

Korean J Pain 2023; 36(1): 113-127

Published online January 1, 2023 https://doi.org/10.3344/kjp.22225

Copyright © The Korean Pain Society.

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

Matheus Soldatelli1,2 , Álvaro de Oliveira Franco2 , Felipe Picon2,3,4 , Juliana Ávila Duarte1,5 , Ricardo Scherer2 , Janete Bandeira2 , Maxciel Zortea2 , Iraci Lucena da Silva Torres6 , Felipe Fregni7 , Wolnei Caumo1,2,7,8

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

Correspondence to:Wolnei Caumo
Laboratory of Pain and Neuromodulation at Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350 - Rio Branco, Porto Alegre 90035-003, Brazil
Tel: +55-51-3359-8083, Fax: +55-51-3359-8083, E-mail: wcaumo@hcpa.edu.br

*These authors contributed equally to this work.

Handling Editor: Young Hoon Kim

Received: July 4, 2022; Revised: November 9, 2022; Accepted: November 9, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Resting-state functional connectivity (rs-FC) may aid in understanding the link between pain-modulating 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.
Methods: 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.
Results: 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.
Conclusions: 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.

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