Chronic pain-induced functional and structural alterations in the brain: a multi-modal meta-analysis.

Chronic pain is a debilitating condition associated with brain alterations. However, the variability in neuroimaging results across modalities necessitates a comprehensive multi-modal meta-analysis for a cohesive understanding. This study aims to elucidate brain alterations in chronic pain patients using a multi-modal meta-analysis approach encompassing structural, resting-state functional connectivity, and pain processing paradigms in functional magnetic resonance imaging. A systematic literature search was conducted across PubMed, OVID Embase, OVID Medline, and Web of Science, encompassing studies published up to May 30^th, 2022, to identify relevant research articles on chronic pain and MRI techniques in three modalities. Inclusion criteria encompassed experiments reporting three modality brain alterations in chronic pain patients, with sufficient statistical thresholds and enough sample size. We conducted voxel-wise meta-analyses using seed-based d mapping to identify significant alterations in each modality. Additionally, conjunction analyses were executed to identify common alterations across these modalities. Ultimately, 47 structure studies, 37 resting state functional connectivity studies, and 41 pain-processing studies were selected for formal analysis. Chronic pain patients displayed notable structural and functional alterations in the insular cortex, characterized by reduced gray matter, disruptions in functional connectivity with the frontoparietal network, and enhanced activation during painful stimuli processing. Distinct activation patterns were observed in the left and right insular cortex for pain stimulus processing versus anticipation. Furthermore, the superior temporal gyrus and superior frontal gyrus exhibited joint alterations across modalities. This multi-modal meta-analysis reveals consistent brain alterations in chronic pain patients, shedding light on the complex interplay between structural and functional changes. PERSPECTIVE: This multi-modal meta-analysis integrates findings from structural, resting-state functional connectivity, and pain processing paradigms in fMRI, revealing consistent brain alterations in chronic pain patients. Notable brain changes highlight the intricate interplay between structural and functional brain changes, advancing our understanding of chronic pain's neural underpinnings.