We report the case of a middle-aged woman who developed trigeminal neuralgia as a sequela of multiple sclerosis (MS). The trigeminal neuralgia was refractory to medications and persisted for two years. Eventually, it was resolved by a mandibular nerve block followed by natalizumab administration. The pain was controlled for 23 months, and additional nerve blocks were not required during this period. It has been previously reported that natalizumab therapy improves the Expanded Disability Status Scale (EDSS) scores and health-related quality of life in patients with MS. In the present case, natalizumab may have prolonged the effect of the mandibular nerve block and consequently improved the patient's quality of life.