Martha López-Canul, Anahita Oveisi, Qianzi He, Maria Luisa Vigano, Antonio Farina, Stefano Comai, Gabriella Gobbi
{"title":"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。","authors":"Martha López-Canul, Anahita Oveisi, Qianzi He, Maria Luisa Vigano, Antonio Farina, Stefano Comai, Gabriella Gobbi","doi":"10.1093/ijnp/pyaf017","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuropathic Pain impairs Sleep Architecture, NREM sleep and Reticular Thalamic Neuronal activity.\",\"authors\":\"Martha López-Canul, Anahita Oveisi, Qianzi He, Maria Luisa Vigano, Antonio Farina, Stefano Comai, Gabriella Gobbi\",\"doi\":\"10.1093/ijnp/pyaf017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":14134,\"journal\":{\"name\":\"International Journal of Neuropsychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-03-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Neuropsychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ijnp/pyaf017\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuropsychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ijnp/pyaf017","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
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.
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.