Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons
Mohammad‐Reza Ghovanloo, Philip R. Effraim, Jun‐Hui Yuan, Betsy R. Schulman, Deborah S. Jacobs, Sulayman D. Dib‐Hajj, Stephen G. Waxman
Abstract
Mechanisms underlying pain after axonal injury remain elusive. A small subgroup of patients experience pain after corneal refractive surgery, providing a human pain model after well-defined injury to axons. Here we analyze a mutation (P610T) in Nav1.7, a threshold sodium channel expressed in nociceptors, found in two siblings with persistent ocular pain after refractive surgery. We show that it impairs channel slow inactivation, thereby triggering inappropriate repetitive activity in trigeminal ganglion axons that signal eye pain.
Topics & Concepts
NociceptorTrigeminal ganglionAxonNociceptionMedicineNeuroscienceTrigeminal nerveSodium channelAnesthesiaSensory systemPsychologyAnatomyReceptorChemistryInternal medicineSodiumOrganic chemistryPain Mechanisms and TreatmentsBotulinum Toxin and Related Neurological DisordersOcular Surface and Contact Lens