OBJECTIVE: The etiology of trigeminal neuralgia (TN) without neurovascular conflict (NVC) is unknown, and classic neurovascular decompression procedures are not applicable. We analyzed a potential etiology in patients operated on for TN without NVC. METHODS: Clinical, radiological, and treatment outcome data were retrospectively reviewed in a consecutive cohort of 37 patients with medically intractable TN without detectable NVC on preoperative 3T magnetic resonance imaging or during surgery. All patients underwent endoscopic-assisted microsurgical trigeminal nerve release from tethering arachnoid between January 2019 and December 2023. Intraoperative findings were compared with findings of a control group of 22 patients undergoing surgery for other pathologies within the cerebellopontine angle. RESULTS: Median age of 24 women and 13 men with TN was 58 years (interquartile range 48-71 years). Mean preoperative pain intensity scores on the visual analog scale and Barrow Neurological Institute scale were 9.5/10 and V, respectively. Surgical exploration revealed an arachnoid-nerve conflict in all cases of TN (cohort group) and in only 2 patients in the control group (P <
0.002). Release of the trigeminal nerve from its anchoring arachnoid yielded significant postoperative improvement of visual analog scale score (1.6/10, P <
0.002), and 84% of patients with TN became pain-free and medication-free (Barrow Neurological Institute score I) after a median postoperative follow-up of 24 months (interquartile range 7-46 months). CONCLUSIONS: Arachnoid-nerve conflict seems to play a pivotal role in the etiology of TN without NVC. Trigeminal nerve release from tethering arachnoid effectively achieves pain relief and medication independence.