467: Electrophysiological Evidence of Systemic Neural Hyperexcitability in Primary Trigeminal Neuralgia

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary orofacial pain, Electrophysiology, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS)

Background and Aims: Background: Primary trigeminal neuralgia (TN) is a representative neuropathic facial pain disorder and is classified into classical TN, associated with neurovascular compression, and idiopathic TN, in which no clear etiology is identified. Increasing evidence, including the identification of pathogenic genetic variants within the sensory electrogenisome, supports a multifactorial pathophysiology that converges on neuronal hyperexcitability, which may extend beyond the trigeminal nerve, reflecting a more generalized axonal predisposition.
Objective: To investigate whether patients with trigeminal neuralgia exhibit generalized axonal hyperexcitability detectable in peripheral motor nerves, and to assess the influence of sodium channel–blocking therapy on axonal excitability parameters.

Methods: Motor nerve excitability testing was performed on the median nerve in 35 patients with classical or idiopathic TN and compared with 35 controls. The strength–duration time constant (SDTC), as an index of persistent sodium conductance, was the primary outcome measure. Secondary outcomes included recovery cycle and threshold electrotonus parameters. Subgroup analyses compared treated versus untreated patients and classical versus idiopathic TN.

Results: Patients showed a significant prolongation of SDTC compared with controls; this difference remained significant after adjustment for age and was evident irrespective of treatment. Superexcitability was significantly attenuated in patients receiving sodium channel blockers compared with untreated patients. No differences in excitability parameters were observed between classical and idiopathic TN.

Conclusions: Patients with TN exhibit evidence of generalized axonal hyperexcitability, detectable in a peripheral motor nerve and characterized by increased persistent sodium conductance. This finding supports the hypothesis of an intrinsic predisposition to neuronal hyperexcitability in TN, independent of neurovascular compression. Sodium channel–blocking therapy modulates superexcitability but does not normalize SDTC, highlighting distinct pharmacodynamic effects. These results suggest that generalized membrane vulnerability may represent a common pathophysiological substrate in both classical and idiopathic TN.

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Presenting Author: andrea truini
Submitting Author: Caterina Maria Leone

Senior Author: andrea truini

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• andrea truini: MD, PhD - Sapienza University
• enrico evangelisti: MD - Sapienza university