Background: Trigeminal neuralgia (TN) is more common in multiple sclerosis (MS) patients than in the general population, likely due to demyelination impacting the trigeminal pathways. While brainstem lesions are associated with MS-TN, their precise role remains unclear. Methods: This study investigates the relationship between brainstem MS plaque location, TN symptoms, and treatment response. We retrospectively analyzed brain MRIs of MS-TN patients, segmenting and coregistering brainstem plaques in MNI space. A tractographic atlas of the trigeminal system was generated using high-resolution diffusion imaging from 30 patients. Lesion involvement was determined by intersection with the trigeminal tract, and its association with pain intensity and treatment outcomes was analyzed using linear regression. Results: Our research revealed 83% of MS-TN patients had brainstem lesions near the fourth ventricle. No single lesion hot spot was identified. Lesion volume did not predict symptom recurrence or treatment response. However, 97% of lesions intersected the trigeminal tract, supporting its association with TN symptoms. Conclusions: The strong overlap between lesions and the trigeminal tract suggests a potential pain generator in MS-TN. Further research is needed to determine whether similar lesions exist in asymptomatic MS patients and to confirm this hypothesis. Future studies will explore whether tract involvement better predicts clinical response to treatment.