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丘脑室旁核-边缘前皮层神经环路在糖尿病痛性病变痛觉过敏的机制研究

中文摘要英文摘要

糖尿病周围神经病变(Diabetic Peripheral Neuropathy ,DPN)是糖尿病患者常见的并发症之一,严重影响患者的生活质量。近年来,关于DPN的发病机制的研究逐渐揭示了中枢神经系统在疼痛感知中的重要作用。研究旨在探讨DPN的神经机制,重点分析室旁丘脑(Paraventricular Thalamus,PVT)和前额叶皮层(Paraventricular Thalamus,PrL)中谷氨酸能神经元的作用。采用链脲佐菌素诱导建立DPN小鼠模型,通过体内光纤光度测定技术监测PVT和PrL谷氨酸神经元对伤害性刺激的反应,结合光遗传学和化学遗传学手段对相关神经元进行特异性调控,评估其对疼痛行为的影响。结果显示,DPN小鼠在机械性刺激下表现出明显的痛觉敏感,PVT和PrL谷氨酸能神经元活动显著增强,干预PVT和PrL谷氨酸能神经元可显著改善DPN小鼠的疼痛行为,进一步研究明确了PVT-PrL神经环路在DPN相关疼痛调节中的关键作用。研究为理解DPN相关神经环路提供了新的见解,并为临床干预提供了潜在的治疗靶点,提示靶向PVT和PrL可能为管理慢性疼痛提供新的治疗策略。

iabetic peripheral neuropathy (DPN) is one of the most common complications in patients with diabetes and seriously affects their quality of life. In recent years, research on the pathogenesis of DPN has increasingly revealed the important role of the central nervous system in pain perception. This study aims to investigate the neural mechanisms of DPN, focusing on the role of glutamatergic neurons in the paraventricular thalamus (PVT) and the prelimbic cortex (PrL). A DPN mouse model was established using streptozotocin (STZ) induction. In vivo fiber photometry was used to monitor the response of glutamatergic neurons in the PVT and PrL to nociceptive stimuli. Optogenetic and chemogenetic approaches were employed to specifically regulate these neurons and assess their effects on pain behaviors. The results showed that DPN mice exhibited significant mechanical hypersensitivity, accompanied by markedly increased activity of glutamatergic neurons in the PVT and PrL. Interventions targeting glutamatergic neurons in the PVT and PrL significantly alleviated pain behaviors in DPN mice. Further studies confirmed the critical role of the PVT-PrL neural circuit in DPN-related pain modulation. This research provides new insights into the neural circuitry underlying DPN and offers potential therapeutic targets for clinical intervention, suggesting that targeting the PVT and PrL may provide novel strategies for managing chronic pain.

刘雅静、张弘弘、胡吉

苏州大学附属第二医院,苏州,215000苏州大学附属第二医院,苏州,215000苏州大学附属第二医院,苏州,215000

神经病学、精神病学基础医学医学研究方法

神经科学糖尿病痛性病变丘脑室旁核前额叶皮层神经环路

neurosciencediabetic painful neuropathyparaventricular thalamic nucleusprefrontal cortexneural circui

刘雅静,张弘弘,胡吉.丘脑室旁核-边缘前皮层神经环路在糖尿病痛性病变痛觉过敏的机制研究[EB/OL].(2025-06-25)[2025-06-26].http://www.paper.edu.cn/releasepaper/content/202506-110.点此复制

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