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

Matheus Soldatelli; Álvaro de Oliveira Franco; Felipe Picon; Juliana Ávila Duarte; Ricardo Scherer; Janete Bandeira; Maxciel Zortea; Iraci Lucena da Silva Torres; Felipe Fregni; Wolnei Caumo

doi: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

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

Authors

Matheus Soldatelli^{1

2}, Álvaro de Oliveira Franco², Felipe Picon^{2

3

4}, Juliana Ávila Duarte^{1

5}, Ricardo Scherer², Janete Bandeira², Maxciel Zortea², Iraci Lucena da Silva Torres⁶, Felipe Fregni⁷, Wolnei Caumo^{1

2

7

8}

Affiliations

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

Abstract

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..