AUTHOR=Butry Lionel , Thomä Johanna , Elsenbruch Sigrid , Icenhour Adriane , Rehmann Robert , Enax-Krumova Elena , Schlaffke Lara 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1672542

DOI=10.3389/fnins.2025.1672542

ISSN=1662-453X

ABSTRACT=IntroductionIdentifying 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.MethodsFollowing the preregistration (PROSPERO CRD42024542390), 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.ResultsA 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 1,592. 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 (I2: 1–76%) and structural (I2: 68–97%) topology studies. Most functional (50%) and structural (65%) topology studies showed some concern regarding the risk of bias.DiscussionThe meta-analyses indicate that functional but not structural whole-brain topological reorganisation is involved in the pathophysiology of chronic pain.