Nav1.8 Variant I206M as a Latent Susceptibility Factor in Postaxotomy Ocular Pain

Although subtle, the p.I206M activation shift may lower the excitability threshold of trigeminal neurons. In the context of axotomy-induced remodeling of the electrogenisome, such variants may act as latent susceptibility factors for chronic ocular pain. Together with prior findings of Nav1.7, TRPV1, and TRPM8 variants in this same cohort, these results support a multihit model, in which rare gain-of-function ion channel variants combine with nerve injury to drive persistent pain after injury, in this instance a second injury, to distal trigeminal axons. Given recent clinical validation of Nav1.8 as an analgesic target, this work further highlights the translational significance of Nav1.8 in human pain disorders.