PurposeTrigeminal neuralgia (TN) is a devastating chronic pain disorder, defined by unilateral shock like pain in at least one division of the trigeminal nerve. Although several studies have investigated structural brain plasticity in TN patients, treatment-induced alterations remain largely uninvestigated. Materials/MethodsCombining T1-weighted magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) and multiple-regression analyses, we assessed gray matter maps of TN patients to investigate changes in gray matter volume (GMV) from before to half a year after stereotactic radiosurgery (SRS). ResultsComparing pre- and post-GMV of 25 TN patients (16 females; mean age 67 years) did not yield any significant clusters, suggesting that the impact of SRS intervention itself on gray matter structure may be negligible. In relation to SRS-induced pain-relief, we found a significant GMV increase in the left superior frontal gyrus associated with greater degrees of pain relief (p=0.024), and a trend toward an increase in GMV in the left dorsolateral prefrontal cortex (p=0.097). ConclusionIn this pilot study, we observed significant increases of GMV in the left superior frontal gyrus with SRS-induced improvements in pain, and a trend for the dorsolateral prefrontal cortex. Future studies are indicated to validate these findings and determine whether SRS-induced decrease in distracting pain events and subsequent increases in GMV result in improved functionality, decreased dependence on "top-down" control, and improved cognitive/executive balance with amelioration of pain events.