Liu Yen-Chin, Chiu Bo-Ya, Tu Kuan-Yi, Liu I-Chen, Chen Shiou-Lan
School of Post-Baccalaureate, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung, Taiwan.
Department of Anesthesiology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, KMU, Kaohsiung, Taiwan.
Eur J Pain. 2025 Jul;29(6):e70039. doi: 10.1002/ejp.70039.
Sleep apnea is a condition that disrupts physiological homeostasis, leading to neuronal dysfunction and triggering a cascade of neurobiological effects. Individuals with sleep apnea and related disturbances may experience increased anxiety and sensory dysfunction, though these phenomena remain underexplored.
In this study, we used a mouse model to examine the effects of sleep apnea-induced intermittent hypoxia (IH) on sensory function and the mechanisms underlying chronic IH. Mice were exposed to chronic IH for 10 days to assess neuronal inflammation and neuronal plasticity changes in key areas such as the spinal cord and periaqueductal grey (PAG) to understand how IH alters sensory conduction pathways.
Our analysis revealed that in mice exposed to IH, astrocytes and microglia were significantly upregulated in the dorsal and ventral horns of the lower spinal cord, accompanied by elevated cytokine levels (IL-1β and TNF-α), suggesting an inflammatory response. Moreover, a significant increase in astrocyte cells within the PAG was also found. Furthermore, chronic IH was associated with increased glutamate receptor subunit GluN2B expression in the spinal cord.
These findings collectively suggest that neuronal inflammation and alterations in synaptic plasticity are central to the development of hyperalgesia in IH-exposed mice. Our results provide crucial mechanistic insights into how IH can induce heightened pain sensitivity and underscore the importance of early therapeutic intervention to address sensory complications in patients with chronic sleep apnoea.
Our study is the first to demonstrate that increased glial cells and elevated NMDA GluN2B expression in the spinal cord and PAG may drive sleep-related IH-induced hyperalgesia, linking sleep apnea to heightened pain sensitivity. Targeting central nervous system inflammation or GluN2B receptors could be crucial for mitigating the health impacts of sleep apnea.
睡眠呼吸暂停是一种破坏生理稳态的病症，会导致神经元功能障碍并引发一系列神经生物学效应。患有睡眠呼吸暂停及相关紊乱的个体可能会出现焦虑增加和感觉功能障碍，不过这些现象仍未得到充分研究。
在本研究中，我们使用小鼠模型来研究睡眠呼吸暂停诱导的间歇性低氧（IH）对感觉功能的影响以及慢性IH的潜在机制。将小鼠暴露于慢性IH环境10天，以评估脊髓和导水管周围灰质（PAG）等关键区域的神经元炎症和神经元可塑性变化，从而了解IH如何改变感觉传导通路。
我们的分析表明，暴露于IH的小鼠中，脊髓下段背角和腹角的星形胶质细胞和小胶质细胞显著上调，同时细胞因子水平（IL-1β和TNF-α）升高，提示存在炎症反应。此外，还发现PAG内的星形胶质细胞显著增加。此外，慢性IH与脊髓中谷氨酸受体亚基GluN2B表达增加有关。
这些发现共同表明，神经元炎症和突触可塑性改变是IH暴露小鼠痛觉过敏发展的核心。我们的结果为IH如何诱导疼痛敏感性增强提供了关键的机制见解，并强调了早期治疗干预以解决慢性睡眠呼吸暂停患者感觉并发症的重要性。
我们的研究首次表明，脊髓和PAG中胶质细胞增加以及NMDA GluN2B表达升高可能会导致与睡眠相关的IH诱导的痛觉过敏，将睡眠呼吸暂停与疼痛敏感性增强联系起来。针对中枢神经系统炎症或GluN2B受体可能对减轻睡眠呼吸暂停对健康的影响至关重要。
