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Potassium channel dysfunction and distinct sensory axonal profiles in painful type 2 diabetes

Cindy Shin-Yi Lin¹, Jowy Tani², Ting Wei Hsu³

¹Central Clinical School, Faculty of Medicine and Health, Brain & Mind Centre, University of Sydney, Sydney, Australia; Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology

|November 30, 2025

Abstract

Objective:

This study aims to characterize sensory axonal changes in patients with non-painful and painful type 2 diabetes mellitus (T2DM) to explore the mechanisms underlying diabetic neuropathic pain in relation to pregabalin treatment.

Methods:

Clinical evaluations, including nerve conduction studies, nerve excitability testing (NET) and visual analogue scale (VAS), were conducted on 200 T2DM, resulting 131 qualifying for inclusion. Cohort stratification utilized VAS scores: 43 had VAS ≥ 4 (painful), and 88 had VAS < 4 (non-painful). The painful cohort was categorized into low pain (4 ≤ VAS < 7) and high pain (VAS ≥ 7). A subgroup receiving pregabalin (15) was assessed to investigate neurophysiological differences.

Results:

The painful cohort differed significantly from the non-painful cohort in sensory nerve excitability parameters including stimulus for 50% maximum amplitude, refractoriness, superexcitability, subexcitability, and depolarization thresholds. Higher VAS scores correlated with reduced TEd⁴⁰(Accom) and TEh(overshoot). Pregabalin-treated patients demonstrated improved stimulus-response slope, S2 accommodation and TEd⁴⁰(Accom) compared to untreated patients.

Conclusions:

Our findings suggest that diabetic neuropathic pain may be associated with axonal hyperpolarization and accommodative properties with implications to potassium channel dysfunction.

Significance:

These findings elucidate mechanisms of diabetic pain pathophysiology, highlighting the clinical significance of sensory NET and the role of potassium channel modulation in T2DM pain management.

Keywords:

Diabetic neuropathy K(+) channels K-ATP Pain Pregabalin Sensory axonal excitability

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