Neuroimaging is a powerful tool to investigate potential associations between chronic pain and brain structure. However, the proliferation of studies across diverse chronic pain syndromes and heterogeneous results challenges data integration and interpretation. We conducted a preregistered anatomic likelihood estimate meta-analysis on structural magnetic imaging studies comparing patients with chronic pain and healthy controls. Specifically, we investigated a broad range of measures of brain structure as well as specific alterations in gray matter and cortical thickness. A total of 7,849 abstracts of experiments published between January 1, 1990 and April 26, 2021 were identified from eight databases and evaluated by two independent reviewers. Overall, 103 experiments with a total of 5,075 participants met the pre-registered inclusion criteria. After correction for multiple comparisons using the gold standard family-wise error correction (p < .05), no significant differences associated with chronic pain were found. However, exploratory analyses using threshold-free cluster enhancement revealed several spatially distributed clusters showing structural alterations in chronic pain. The majority of clusters coincided with regions implicated in nociceptive processing including the amygdala, thalamus, hippocampus, insula, anterior cingulate cortex and inferior frontal gyrus. Taken together, these results suggest that chronic pain is associated with subtle, spatially distributed alterations of brain structure.
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