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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

潘吕辣^1,2, 巩涛³, 李子昂^1,2, 邱欣彤², 张明明², 李云庆^1,2,3,*

¹郑州大学基础医学院，郑州 450001；²空军军医大学基础医学院人体解剖学与组织胚胎学教研室暨梁銶琚脑研究中心，西安 710032；³包头医学院人体解剖学教研室，包头 014000

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。

关键词： 蓝斑; 屏状核; 岛叶; 神经病理性痛

The involvement of claustrum/insular cortex-locus coeruleus neural pathway in modulating neuropathic pain in mice

PAN Lyu-La^1,2, GONG Tao³, LI Zi-Ang^1,2, QIU Xin-Tong², ZHANG Ming-Ming², LI Yun-Qing^1,2,3,*

¹Basic Medical School, Zhengzhou University, Zhengzhou 450001, China；²Department of Anatomy and K.K. Leung Brain Research Centre, School of Basic Medicine, Air Force Military Medical University, Xi'an 710032, China；³Department of Anatomy, Baotou medical college, Baotou 014000, China

Abstract

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.

Key words: Locus coeruleus; claustrum; insular cortex; neuropathic pain

收稿日期：　　录用日期：

通讯作者：李云庆　　E-mail:

DOI: 10.13294/j.aps.2026.0018

引用本文：

潘吕辣, 巩涛, 李子昂, 邱欣彤, 张明明, 李云庆. 小鼠屏状核/岛叶-蓝斑神经通路参与调节神经病理性痛[J]. 生理学报 2026; 78 (1): 148-158.

PAN Lyu-La, GONG Tao, LI Zi-Ang, QIU Xin-Tong, ZHANG Ming-Ming, LI Yun-Qing. The involvement of claustrum/insular cortex-locus coeruleus neural pathway in modulating neuropathic pain in mice. Acta Physiol Sin 2026; 78 (1): 148-158 (in Chinese with English abstract).