Objective:To explore the pathogenesis of glossopharyngeal neuralgia (GPN) in central nervous system from perspective of brain morphology.Methods:A prospective study was performed. Twenty-seven patients with right primary GPN admitted to Department of Neurosurgery, People's Hospital of Peking University from April 2019 to June 2023 and 27 healthy subjects (controls) matched with age, gender, dominant hand, and education level during the same period were recruited. These patients were divided into GPN with neurovascular compression group ( n=18) and GPN without neurovascular compression ( n=9) based on intraoperative presence of neurovascular compression. SPM8 software based on Matlab R2017b programming platform and VBM8 toolbox were used to process the whole-brain high-resolution 3D-T1 brain structural image data of the participants and analyze the differences in the gray matter volume of each brain region between the 2 groups. Pearson correlation was applied to analyze the correlations of gray matter volumes in brain regions enjoying significant difference with baseline data and pain characteristics of these GPN patients. Results:Compared with controls, patients with GPN had significantly reduced gray matter volumes in the left anterior cingulate gyrus, middle temporal gyrus, transverse temporal gyrus, precentral gyrus, postcentral gyrus, right insula, thalamus, inferior parietal lobule, precentral gyrus, middle temporal gyrus, and inferior temporal gyrus ( P<0.05, FDR corrected). Compared with GPN patients with neurovascular compression, GPN patients without neurovascular compression had significantly reduced gray matter volume in the bilateral anterior cingulate gyrus ( P<0.05, FDR corrected). Changes of gray matter volume in the right insula were negatively correlated with disease duration of GPN patients ( r=-0.521, P=0.005). Conclusion:GPN patients have extensive gray matter atrophy in the brain, which may play an essential role in GPN development and maintenance.