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

Area of Science:

• Neuroscience
• Genetics
• Pain Research

Background:

• Persistent ocular pain can occur after corneal refractive surgery, damaging trigeminal nerve axons.
• The role of specific ion channel variants in this condition is not fully understood.

Purpose of the Study:

• To investigate the functional role of a Nav1.8 (SCN10A) variant, c.618A > G (p.I206M), in the pathogenesis of post-LASIK ocular pain.

Main Methods:

• Whole-exome sequencing identified the p.I206M variant in patients with ocular pain.
• Functional characterization using patch-clamp electrophysiology, computational modeling, and multielectrode array (MEA) recordings in rat trigeminal neurons.

Main Results:

• The p.I206M variant caused a ~5 mV hyperpolarizing shift in Nav1.8 activation.
• MEA recordings showed increased trigeminal neuron firing frequency at physiological temperatures for the p.I206M variant.
• Computational modeling predicted increased neuronal excitability, attenuated under heterozygous conditions.

Conclusions:

• The subtle Nav1.8 p.I206M variant may lower trigeminal neuron excitability thresholds.
• This variant could act as a susceptibility factor for chronic ocular pain, especially when combined with nerve injury.
• Findings support a multihit model involving rare ion channel variants and nerve injury in persistent pain, highlighting Nav1.8 as a potential analgesic target.