Emerging Pharmacological Strategies for Trigeminal Neuralgia

Trigeminal neuralgia can be a debilitating pain condition that affects women more frequently than men and for which there are only limited therapeutic avenues. Trigeminal neuralgia can either be idiopathic (where there is no clearly identifiable cause), classical (which typically involves neurovascular compression of the trigeminal root entry zone) or secondary which results from nerve damage due to other causes. First-line treatments for trigeminal neuralgia include the sodium channel blockers carbamazepine and oxcarbazepine, whose mechanism of action is to stabilize the inactivated state of sodium channels, thereby reducing the electrical activities of trigeminal neurons. Second-line treatments include gabapentinoids, which act on Cavα2δ subunits of high voltage activated calcium channels to inhibit synaptic transmission in the trigeminal pain pathway. Both of these treatment avenues exhibit a number of adverse effects and many patients are refractory. Hence, new avenues for combatting trigeminal neuralgia are needed. In this review article, we discuss clinical evidence for efficacy and benefits of novel pharmacological treatment approaches for trigeminal neuralgia, including the inhibition of CGRP receptors, activation and desensitization of TRPV1 channels, the development of new generations of sodium channel blockers, and the use of botulinum toxin. We conclude that while there are potential benefits of these approaches, larger well-controlled cohort studies are needed to provide a definitive answer.