Neuropathic Pain impairs Sleep Architecture, NREM sleep and Reticular Thalamic Neuronal activity.

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY
Martha López-Canul, Anahita Oveisi, Qianzi He, Maria Luisa Vigano, Antonio Farina, Stefano Comai, Gabriella Gobbi
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Abstract

Background: Neuropathic pain (NP) is a chronic and debilitating condition frequently comorbid with insomnia. However, the alterations in sleep architecture under NP conditions and the mechanisms underlying both pain and sleep disturbances remain poorly understood. The reticular thalamic nucleus (RTN) plays a crucial role in non-rapid eye movement sleep (NREMS) and pain processing, but its involvement in NP-related sleep disruptions has not been fully elucidated.

Methods: To investigate sleep-related electrophysiological changes in NP, we performed continuous 24-hour EEG/EMG recordings in rats exhibiting allodynia following L5-L6 spinal nerve lesions. Additionally, we assessed the in vivo neuronal activity of the RTN in both NP and sham-operated control rats. Spectral analyses were conducted to examine alterations in sleep oscillatory dynamics. RTN neuronal responses to nociceptive pinch stimuli were classified as increased, decreased, or unresponsive.

Results: NP rats exhibited a significant reduction in NREMS (-20%, p < 0.001) and an increase in wakefulness (+19.13%, p < 0.05) compared to controls, whereas rapid eye movement sleep (REMS) remained unchanged. Sleep fragmentation was pronounced in NP animals (p < 0.0001), with frequent brief awakenings, particularly during the inactive/light phase. Spectral analysis revealed increased delta and theta power during both NREMS and REMS. RTN neurons in NP rats displayed a higher basal tonic firing rate, along with increased phasic activity (number of bursts), although the percentage of spikes in bursts remained unchanged.

Conclusions: NP is characterized by disrupted sleep architecture, reduced NREMS, and heightened RTN neuronal firing activity with partial compensation of burst activity. Given that RTN burst activity is essential for optimal NREMS, its disruption may contribute to NP-induced sleep impairments. These findings suggest that altered EEG signals, alongside dysregulated RTN neuronal activity, may serve as potential brain markers for NP-related insomnia.

神经性疼痛损害睡眠结构、非快速眼动睡眠和丘脑网状神经元活动。
背景:神经性疼痛(NP)是一种慢性衰弱性疾病,经常与失眠并发。然而,人们对 NP 条件下睡眠结构的改变以及疼痛和睡眠障碍的内在机制仍然知之甚少。丘脑网状核(RTN)在非快速眼动睡眠(NREMS)和疼痛处理中发挥着关键作用,但其在 NP 相关睡眠障碍中的参与尚未完全阐明:为了研究 NP 中与睡眠相关的电生理变化,我们对 L5-L6 脊髓损伤后出现异感症的大鼠进行了连续 24 小时的 EEG/EMG 记录。此外,我们还评估了 NP 和假手术对照组大鼠 RTN 的体内神经元活动。我们进行了频谱分析,以研究睡眠振荡动态的变化。RTN神经元对痛觉刺激的反应分为增加、减少或无反应:与对照组相比,NP 大鼠的 NREMS 显著减少(-20%,p < 0.001),觉醒显著增加(+19.13%,p < 0.05),而快速眼动睡眠(REMS)保持不变。NP动物的睡眠片段明显(p < 0.0001),经常出现短暂觉醒,尤其是在非活动/光照阶段。频谱分析显示,NREMS 和 REMS 期间的 delta 和 theta 功率都有所增加。NP 大鼠的 RTN 神经元显示出更高的基础强直性发射率,同时阶段性活动(脉冲串数量)增加,尽管脉冲串中尖峰的百分比保持不变:NP的特点是睡眠结构紊乱、NREMS减少、RTN神经元发射活动增加,但猝发活动得到部分补偿。鉴于 RTN 突发性活动对最佳 NREMS 至关重要,其中断可能会导致 NP 引起的睡眠障碍。这些研究结果表明,改变的脑电信号以及失调的 RTN 神经元活动可作为 NP 相关失眠症的潜在脑标记。
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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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