Menthol preferentially inhibits persistent Na+ current mediated by NaV1.8 in small-sized dural afferent neurons of rats.

IF 1.6 4区医学 Q4 NEUROSCIENCES

Neuroreport Pub Date : 2025-06-24 DOI:10.1097/WNR.0000000000002189

Michiko Nakamura, Il-Sung Jang

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引用次数: 0

Abstract

Objective: Menthol is widely used as a cooling agent and an adjunctive analgesic to relieve various painful conditions, such as migraine. As menthol acts as an agonist for the thermosensitive ion channel transient receptor potential melastatin 8 (TRPM8), other ion channels, such as voltage-gated Na+ channels, are also involved in the antinociceptive effect of menthol. In this study, we explored the effect of menthol on tetrodotoxin-resistant (TTX-R) Na+ channels in nociceptive sensory neurons.

Methods: TTX-R Na+ current (INa) was recorded from acutely isolated rat dural afferent neurons identified with the fluorescent dye DiI using a whole-cell patch-clamp technique.

Results: Under a voltage-clamp condition, menthol potently decreased the amplitude of the persistent TTX-R Na+ current (INa) in a concentration-dependent manner, with a minor effect on the transient current. The inhibition of persistent TTX-R INa by menthol was not affected by the TRPM8 antagonist. Menthol (300 μM) (1) shifted the steady-state fast inactivation relationship to hyperpolarizing ranges without affecting the voltage-activation relationship, (2) accelerated the onset of inactivation, and (3) retarded the recovery from the inactivation of TTX-R Na+ channels. Under the current clamp condition, menthol (300 μM) decreased the threshold for action potential generation but reduced the number of action potentials elicited by strong depolarizing current stimuli.

Conclusion: The results of this study suggest that menthol exerts an analgesic effect by preferentially inhibiting persistent TTX-R INa and modulating the inactivation and recovery kinetics of TTX-R Na+ channels.

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薄荷醇优先抑制大鼠小尺寸硬脑膜传入神经元NaV1.8介导的持续Na+电流。

目的：薄荷醇被广泛用作冷却剂和辅助止痛剂，以缓解各种疼痛状况，如偏头痛。由于薄荷醇作为热敏离子通道瞬时受体电位美拉他汀8 （TRPM8）的激动剂，其他离子通道，如电压门控Na+通道，也参与薄荷醇的抗伤害感受作用。在这项研究中，我们探讨了薄荷醇对河豚毒素抗性（TTX-R） Na+通道的影响。方法：采用全细胞膜片钳技术记录急性分离大鼠硬脑膜传入神经元的TTX-R Na+电流（INa）。结果：在电压箝位条件下，薄荷醇能有效降低TTX-R持续Na+电流（INa）的幅值，且呈浓度依赖性，对瞬态电流影响较小。薄荷醇对持久性TTX-R - INa的抑制作用不受TRPM8拮抗剂的影响。薄荷醇（300 μM）(1)在不影响电压活化关系的情况下将稳态快速失活关系转移到超极化范围；(2)加速失活的开始；(3)延缓TTX-R Na+通道失活后的恢复。在电流箝位条件下，薄荷醇（300 μM）降低了动作电位产生的阈值，但减少了强去极化电流刺激引起的动作电位数量。结论：薄荷醇通过优先抑制持续的TTX-R Na和调节TTX-R Na+通道的失活和恢复动力学来发挥镇痛作用。

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

Neuroreport 医学-神经科学

CiteScore

3.20

自引率

0.00%

发文量

150

审稿时长

1 months

期刊介绍： NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.