Background <p>Chronic temporomandibular disorder (TMD) pain with pain catastrophizing (PC) is associated with altered brain morphology; however, its neuroanatomical underpinnings remain unclear. This study aimed to investigate gray matter volume (GMV) in the brain regions of chronic TMD pain patients with PC using voxel-based morphometry.</p> Methods <p>A case-control study was conducted with 28 participants, including 14 chronic TMD pain patients with high PC and 14 age- and sex-matched healthy controls. T1-weighted magnetic resonance imaging (MRI) data were acquired using a 3-Tesla scanner and analyzed with Statistical Parametric Mapping 12 (SPM12). Whole-brain and Region-of-Interest (ROI) analyses were performed to assess GMV differences and associations between GMV with clinical variables.</p> Results <p>Whole-brain analysis revealed no significant GMV differences between groups. However, ROIs analyses showed significantly smaller GMV in the bilateral hippocampus, left parahippocampal gyrus, and right putamen in the patient group. Additionally, GMV in the orbital part of the inferior frontal gyrus was negatively associated with pain duration.</p> Conclusion <p>This study suggests that central nervous system alterations are linked to chronic TMD pain condition with pain catastrophizing. These findings contribute to understanding the neurobiological basis of chronic musculoskeletal pain and highlight the need for further research into the role of cognitive-emotional factors in pain-related neural adaptations.</p> Clinical trial number <p>Not applicable.</p>