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

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 (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.

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 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.

The meta-analyses indicate that functional but not structural whole-brain topological reorganisation is involved in the pathophysiology of chronic pain.