Chronic widespread pain patients show disrupted cortical connectivity in default mode and salience networks, modulated by pain sensitivity

Helene van Ettinger-Veenstra,1,2 Peter Lundberg,1,3–4 Péter Alföldi,5 Martin Södermark,5 Thomas Graven-Nielsen,6 Anna Sjörs,7 Maria Engström,1,4 Björn Gerdle1,51Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; 2Center for Social and Affective Neuroscience (CSAN), Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; 3Department of Radiation Physics, Linköping University, Linköping, Sweden; 4Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; 5Pain and Rehabilitation Centre, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; 6Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Aalborg, Denmark; 7Institute of Stress Medicine, Region Västra Götaland and Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, SwedenPurpose: The remodeling of functional neuronal connectivity in chronic widespread pain (CWP) patients remains largely unexplored. This study aimed to investigate functional connectivity in CWP patients in brain networks related to chronic pain for changes related to pain sensitivity, psychological strain, and experienced pain.Patients and methods: Functional connectivity strength of the default mode network (DMN) and the salience network (SN) was assessed with functional magnetic resonance imaging. Between-group differences were investigated with an independent component analysis for altered connectivity within the whole DMN and SN. Then, changes in connectivity between nodes of the DMN and SN were investigated with the use of a seed-target analysis in relation to the covariates clinical pain intensity, pressure pain sensitivity, psychological strain, and as an effect of experienced experimental cuff-pressure pain.Results: CWP patients showed decreased connectivity in the inferior posterior cingulate cortex (PCC) in the DMN and increased connectivity in the left anterior insula/superior temporal gyrus in the SN when compared to controls. Moreover, higher pain sensitivity in CWP when compared to controls was related to increased connectivity within the SN (between left and right insula) and between SN and DMN (between right insula and left lateral parietal cortex).Conclusion: This study shows that connectivity within the DMN was decreased and connectivity within the SN was increased for CWP. Furthermore, we present a novel finding of interaction of pain sensitivity with SN and DMN-SN functional connectivity in CWP.Keywords: functional connectivity, functional magnetic resonance imaging, fMRI, default node network, DMN, salience networ