Ivabradine reduces neuropathic pain after spinal cord injury by inhibiting excitatory synaptic transmission in the spinal dorsal horn

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-02-06 DOI:10.1016/j.neulet.2025.138113

Nobuko Ohashi , Masayuki Ohashi , Rintaro Hoshino , Hiroyuki Deguchi , Hiroshi Baba

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引用次数: 0

Abstract

Spinal cord injuries (SCIs) can lead to severe neuropathic pain and increased risk of myocardial infarction and heart failure; therefore, the use of analgesics against SCI-induced pain should be minimized because of their adverse effects on the cardiovascular system. Ivabradine, a blocker of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, is used as a bradycardic agent, but recent studies focused on it as an analgesic agent for peripheral neuropathic pain. However, the analgesic effects of ivabradine on central neuropathic pain, such as SCI-induced pain, have not been examined. The aim of this study was to investigate the spinal analgesic effects of ivabradine on central neuropathic pain induced by SCI. Ivabradine induced analgesia in both spontaneous pain-related behavior and mechanical allodynia in SCI-induced pain (6–7 rats/group; p < 0.01). In immunohistochemical staining analyses, ivabradine suppressed phosphorylation of extracellular signal-regulated kinases activated by SCI-induced pain in the superficial spinal dorsal horn (6 rats/group; p < 0.01). In in vitro whole-cell patch-clamp analysis, ivabradine decreased the frequency of miniature excitatory postsynaptic currents in substantia gelatinosa neurons (11–12 rats/group; p < 0.01). We concluded that ivabradine reduces SCI-induced pain by inhibiting excitatory synaptic transmission in the spinal dorsal horn.

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伊伐布雷定通过抑制脊髓背角的兴奋性突触传递减轻脊髓损伤后的神经性疼痛。

脊髓损伤（SCIs）可导致严重的神经性疼痛，增加心肌梗死和心力衰竭的风险；因此，由于镇痛药对心血管系统的不良影响，应尽量减少对sci引起的疼痛的使用。伊伐布雷定是一种超极化激活的环核苷酸门控阳离子（HCN）通道阻滞剂，被用作心动过缓的药物，但最近的研究主要集中在它作为周围神经性疼痛的镇痛药物。然而，伊伐布雷定对中枢神经性疼痛（如sci引起的疼痛）的镇痛作用尚未得到研究。本研究旨在探讨伊伐布雷定对脊髓损伤所致中枢神经性疼痛的镇痛作用。伊伐布雷定诱导自发性疼痛相关行为和机械性疼痛的镇痛(6-7只大鼠/组；p

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

期刊介绍： Neuroscience Letters is devoted to the rapid publication of short, high-quality papers of interest to the broad community of neuroscientists. Only papers which will make a significant addition to the literature in the field will be published. Papers in all areas of neuroscience - molecular, cellular, developmental, systems, behavioral and cognitive, as well as computational - will be considered for publication. Submission of laboratory investigations that shed light on disease mechanisms is encouraged. Special Issues, edited by Guest Editors to cover new and rapidly-moving areas, will include invited mini-reviews. Occasional mini-reviews in especially timely areas will be considered for publication, without invitation, outside of Special Issues; these un-solicited mini-reviews can be submitted without invitation but must be of very high quality. Clinical studies will also be published if they provide new information about organization or actions of the nervous system, or provide new insights into the neurobiology of disease. NSL does not publish case reports.