Classical trigeminal neuralgia (TN) is a specific type of neuropathic orofacial pain of which the plasticity of brain structure and connectivity have remained largely unknown. A total of 62 TN patients were included and referred to MRI scans. Voxel-based morphometry was used to analyze the change of gray matter volume. Resting-state functional imaging was used to analyze the connectivity between brain regions. The results showed gray matter volume reduction in components of the prefrontal cortex, precentral gyrus, cerebellar tonsil, thalamus, hypothalamus, and nucleus accumbens among right TN patient and in the inferior frontal gyrus, precentral gyrus, cerebellum, thalamus, ventral striatum, and putamen among left TN patients. The connections between the right superior frontal gyrus and right middle frontal gyrus were lower in right TN patients. The connection between the left precentral gyrus and the left superior frontal gyrus was lower while the connection between bilateral thalamus was higher in left TN patients. The changes of volume in bilateral thalamus of right TN patients and left ventral striatum of left TN patients, and the connectivity between bilateral thalamus of left TN patients were moderately correlated with pain duration. These findings suggest that brain regions such as the thalamus may not only be involved in processing of pain stimuli but also be important for the development of TN. The left hemisphere may be dominant in processing and modulation of TN pain signal. Chronification of TN induces volume changes in brain regions which are associated with emotional or cognitive modulation of pain. Hum Brain Mapp 39:609-621, 2018. © 2017 Wiley Periodicals, Inc.