Brain network properties in chronic pain – a systematic review and meta-analysis of graph-based connectivity metrics

Lionel Butry^1*Johanna Thomä¹Sigrid Elsenbruch^2,3Adriane Icenhour⁴Robert Rehmann¹Elena Enax-Krumova¹Lara Schlaffke^1,5

• ¹Department of Neurology, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany
• ²Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
• ³Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
• ⁴Department of Affective Neuroscience, Ruhr University Bochum, Bochum, Germany
• ⁵BG University Hospital Bergmannsheil, Heimer Institute for Muscle Research, Bochum, Germany

Identifying brain topology alterations in chronic pain is a crucial step in understanding its pathophysiology. The primary objective of this systematic review and meta-analysis was to assess alterations in resting-state functional and structural global network properties in patients with chronic pain. Following the preregistration, databases were searched for studies comparing connectivity-based whole-brain global network properties between patients with chronic pain and healthy controls. Risk of bias was assessed using an adapted Newcastle-Ottawa scale. Random-effect meta-analyses were conducted for each global network property separately. A total of 32 functional topology studies and 17 structural topology studies were included in the qualitative review, with 27 functional topology studies and 17 structural topology studies eligible for meta-analysis across nine unique structural and functional global network properties. The number of participants per meta-analysis ranged from 178 to 1592. There was low-certainty evidence that chronic pain patients showed impairments in local efficiency of resting-state functional whole-brain topology (SMD: -0.50, 95%-CI: -0.81 to -0.19, 95%- PI: -1.38 to 0.38), and low to very low-certainty evidence that structural whole-brain topology was not altered in chronic pain across nine global network properties. The heterogeneity was high in the majority of functional (I^2: 1% – 76%) and structural (I^2: 68% – 97%) topology studies. Most functional (50%) and structural (65%) topology studies showed some concern regarding the risk of bias. The meta-analyses indicate that functional but not structural whole-brain topological reorganisation is involved in the pathophysiology of chronic pain.