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

IF 3.4 3区医学 Q1 CLINICAL NEUROLOGY

Clinical Neurophysiology Pub Date : 2026-01-01 Epub Date: 2025-11-21 DOI:10.1016/j.clinph.2025.2111450

Cindy Shin-Yi Lin , Jowy Tani , Ting Wei Hsu , Yi-Chen Lin , Yun-Ru Liu , Jia-Ying Sung M.D. PhD.

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引用次数: 0

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.

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疼痛性2型糖尿病的钾通道功能障碍和不同的感觉轴突分布

目的观察非疼痛性和疼痛性2型糖尿病（T2DM）患者感觉轴突的变化，探讨普瑞巴林治疗对糖尿病神经性疼痛的影响机制。方法对200例T2DM患者进行神经传导、神经兴奋性测试（NET）和视觉模拟评分（VAS）等临床评价，其中131例符合纳入标准。队列分层采用VAS评分：43例VAS≥4（疼痛），88例VAS <； 4（无疼痛）。疼痛组分为低疼痛组（4≤VAS < 7）和高疼痛组（VAS≥7）。接受普瑞巴林治疗的亚组（15）评估神经生理差异。结果疼痛组与非疼痛组的感觉神经兴奋性参数有显著差异，包括50%最大振幅的刺激、难阻性、超兴奋性、亚兴奋性和去极化阈值。较高的VAS评分与降低的TEd40（Accom）和TEh（超调）相关。与未治疗的患者相比，接受普瑞巴林治疗的患者表现出更好的刺激反应斜率、S2调节和TEd40（Accom）。结论糖尿病神经性疼痛可能与轴突超极化和调节特性有关，并与钾通道功能障碍有关。这些发现阐明了糖尿病疼痛的病理生理机制，强调了感觉NET的临床意义和钾通道调节在T2DM疼痛管理中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Neurophysiology 医学-临床神经学

CiteScore

8.70

自引率

6.40%

发文量

932

审稿时长

59 days

期刊介绍： As of January 1999, The journal Electroencephalography and Clinical Neurophysiology, and its two sections Electromyography and Motor Control and Evoked Potentials have amalgamated to become this journal - Clinical Neurophysiology. Clinical Neurophysiology is the official journal of the International Federation of Clinical Neurophysiology, the Brazilian Society of Clinical Neurophysiology, the Czech Society of Clinical Neurophysiology, the Italian Clinical Neurophysiology Society and the International Society of Intraoperative Neurophysiology.The journal is dedicated to fostering research and disseminating information on all aspects of both normal and abnormal functioning of the nervous system. The key aim of the publication is to disseminate scholarly reports on the pathophysiology underlying diseases of the central and peripheral nervous system of human patients. Clinical trials that use neurophysiological measures to document change are encouraged, as are manuscripts reporting data on integrated neuroimaging of central nervous function including, but not limited to, functional MRI, MEG, EEG, PET and other neuroimaging modalities.