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小鼠屏状核/岛叶-蓝斑神经通路参与调节神经病理性痛

The involvement of claustrum/insular cortex-locus coeruleus neural pathway in modulating neuropathic pain in mice
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摘要 为了研究屏状核(claustrum,CLA)/岛叶(insular cortex,IC)与蓝斑(locus coeruleus,LC)间的纤维联系及该神经通路在神经病理性痛中的作用,本文利用形态学、膜片钳记录和化学遗传学技术,分别观察小鼠的CLA/IC-LC神经通路、神经病理性痛刺激对CLA/IC神经元电生理特性的影响和调控该通路对痛行为的影响。结果显示:(1)将顺行示踪病毒注入CLA/IC后,在同侧LC内可见病毒顺行标记的纤维和终末;将逆行示踪剂注入LC后,在同侧CLA及IC内可见逆标神经元,而对侧分布较少;(2)在神经病理性痛状态下,CLA/IC-LC投射神经元的突触前递质释放增加,突触后受体反应增强,动作电位的放电数量增加;(3)特异性抑制CLA/IC-LC神经通路能诱发假手术组小鼠产生疼痛反应;特异性兴奋该通路可缓解神经病理性痛小鼠的痛相关行为。上述结果提示,CLA/IC神经元可向LC发出投射,神经病理性痛刺激时,CLA/IC-LC神经通路的活性增强,激活该投射通路能减轻神经病理性痛。 To investigate the fiber connections between the claustrum(CLA)/insular cortex(IC)and the locus coeruleus(LC),as well as the role of this neural pathway in neuropathic pain,morphological techniques,patch-clamp recording,and chemogenetics were used in this study,to observe the CLA/IC-LC neural pathway in mice,the effects of neuropathic pain stimuli on the electrophysiological properties of CLA/IC neurons,and the impact of regulating the pathway on pain behaviors,respectively.The results showed that:(1)After injecting anterograde tracing virus into the CLA/IC,anterogradely labeled fibers and terminals were observed in the ipsilateral LC.When retrograde tracers were injected into the LC,retrogradely labeled neurons were observed in both the ipsilateral CLA/IC,whereas fewer labeled neurons were observed in the contralateral side;(2)In the neuropathic pain state,the presynaptic release of neurotransmitters from CLA/IC-LC projection neurons was increased,postsynaptic receptor responses were enhanced,and the number of action potential discharges was elevated;(3)Specific inhibition of the CLA/IC-LC neural pathway induced pain responses in sham-operated mice;specific activation of this pathway alleviated pain-related behaviors in neuropathic pain mice.The present results indicate the existence of functional projection from the CLA/IC to the LC.Under neuropathic pain condition,the CLA/IC-LC pathway exhibits enhanced neuronal activity,and selective activation of this pathway produces significant analgesic effects against neuropathic pain.
作者 潘吕辣 巩涛 李子昂 邱欣彤 张明明 李云庆 PAN Lyu-La;GONG Tao;LI Zi-Ang;QIU Xin-Tong;ZHANG Ming-Ming;LI Yun-Qing(Basic Medical School,Zhengzhou University,Zhengzhou 450001,China;Department of Anatomy and K.K.Leung Brain Research Centre,School of Basic Medicine,Air Force Military Medical University,Xi'an 710032,China;Department of Anatomy,Baotou medical college,Baotou 014000,China)
出处 《生理学报》 2026年第1期148-158,共11页 Acta Physiologica Sinica
基金 supported by the National Natural Science Foundation of China(No.82130034,82371246,82221001,82471254) the Brain Science and Brain-like Intelligence Technology-National Science and Technology Major Project(No.2021ZD0204403)。
关键词 蓝斑 屏状核 岛叶 神经病理性痛 locus coeruleus claustrum insular cortex neuropathic pain

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