The etiology of classical trigeminal neuralgia (CTN) is still unclear. A better understanding of the cerebral structural and functional changes in female patients with CTN may provide important novel insights into the pathophysiologic mechanisms of female CTN. A total 37 female CTN patients were included and referred to MRI scans, comprising with 19 left CTN and 18 right CTN patients. We analyzed the volume and shape of subcortical gray matter (GM), and the functional connectivity (FC) between the accumbens nucleus (NAc) and whole brain in right and left CTN patients respectively. We found left CTN patients had a reduced right NAc volume compared to controls, similarly, the right CTN had the decreased volume in the left NAc. Vertex-wise shapes of right NAc in left CTN patients showed significant regional shape deformation on the anterior, medial and ventroposterior aspects, in contrast, left NAc of right CTN patients showed significant regional shape deformation on the anterior and posterior aspect. Furthermore, patients with left CTN showed significantly lower FC between the right NAc and right orbitofrontal cortex than control subjects. The volume of NAc in all CTN was significantly related to the perception of present pain intensity. The CTN might be majorly caused by volume reduction in NAc. A greater understanding of the neurobiological basis of pain-related changes in NAc will provide the knowledge for the development of novel NAc based therapeutic targets for pain management or even prevention in CTN patients.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.