• Alina T Henn, Bart Larsen, Lennart Frahm, Anna Xu, Azeez Adebimpe, ScottJ CobbJCDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.VISN4 Mental Illness Research, Education, and Clinical Center, Corporal Michael J. Crescenz VA (Veterans Affairs) Medical Cente, Sophia Linguiti, Vaishnavi Sharma, Allan I Basbaum, Gregory Corder, Robert H Dworkin, Robert R Edwards, Clifford J Woolf, Ute Habel, Simon B Eickhoff, Claudia R Eickhoff, Lisa Wagels, and Theodore D Satterthwaite.
• Department of Psychiatry, Psychotherapy and Psychosomatics, School of Medicine, RWTH Aachen University, Aachen, Germany.
• Pain. 2023 Jan 1; 164 (1): e10e24e10-e24.

AbstractNeuroimaging 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 anatomical 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 7849 abstracts of experiments published between January 1, 1990, and April 26, 2021, were identified from 8 databases and evaluated by 2 independent reviewers. Overall, 103 experiments with a total of 5075 participants met the preregistered inclusion criteria. After correction for multiple comparisons using the gold-standard family-wise error correction ( P < 0.05), 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. Most of the 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.Copyright © 2022 International Association for the Study of Pain.

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