Trigeminal neuralgia (TN) is typically treated pharmacologically with anticonvulsants, but these can be ineffective, or can lose their effectiveness over time. In recent years, botulinum toxin type A (BoNT-A), when injected subcutaneously across multiple sites, can effectively treat TN. However, approximately 30% of TN cases are refractory to subcutaneous BoNT-A treatment. We report here the case of a 79-year-old female patient with TN presenting as severe, episodic pain in the lower left gingival area. She was on anticonvulsant therapy (carbamazepine) for about 3 years prior to BoNT-A treatment. Despite initial relief, the pain not only recurred, but also began to worsen, even as her carbamazepine dose was increased substantially. We injected 50 U of BoNT-A into the oral mucosa of the painful gingival area, but the patient's pain was unaffected. We then changed to an intramuscular injection protocol and injected the same dose of BoNT-A into the left masseter, which produced a good therapeutic effect for about 5 months; she was then administered a second treatment (intra-masseter), and at a 2-week follow-up, still reported being pain-free. This case and a survey of the literature suggest that BoNT-A injection protocols maybe closely correlated with their clinical efficacy in cases of TN, possibly due to the ability of BoNT-A to be transported retrogradely along trigeminal nerve axons. We believe that finding the optimal BoNT-A therapy injection protocol(s) will significantly reduce the number of refractory cases of TN.