Spared Nerve Injury Induces Long-Term and Brain Region-Specific Changes in Oligodendrocyte Density in Mice

IF 3.4 2区医学 Q1 ANESTHESIOLOGY

European Journal of Pain Pub Date : 2026-04-11 DOI:10.1002/ejp.70265

Léa J. Becker, Rory O'Shea, Gustavo Borges, Jordan G. McCall

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Abstract

Background

Emerging evidence suggests a role for non-neuronal cells in the pathophysiology of chronic pain. Chronic pain causes profound alterations of the transcriptomic program of oligodendroglia, but the effect of pain on the oligodendroglial cells themselves remains unknown.

Methods

Male and female C57BL6/J mice underwent spared nerve injury (SNI). Mechanical hypersensitivity was assessed 5 weeks later using the von Frey test. Six weeks post-surgery, mice were perfused, brains dissected, and immunostained for oligodendrocyte precursor cells (OPC) and mature oligodendrocytes (OL) in four brain regions involved in pain chronification: anterior cingulate cortex (ACC), central amygdala (CeA), basolateral amygdala (BLA), and periaqueductal grey (PAG).

Results

We found OL were reduced in the ACC and CeA of both sexes 6 weeks after SNI. Conversely, BLA OL were increased in both sexes following SNI. There was a sex-dependent effect of SNI on PAG-OL, where OL were only reduced in females. SNI did not affect OPC in any of the studied brain regions, but female PAG and BLA appeared to have fewer OPC than males independent of SNI.

Conclusion

Long-term nerve injury differentially affects OL in a brain region- and sex-dependent manner. This effect is observable 6 weeks after injury, suggesting a long-lasting impact of chronic pain on oligodendroglial cells. OPC, on the other hand, are remarkably stable. This finding aligns with previous literature showing OPC maintain homeostasis, even in pathological conditions.

Significance

Oligodendrocytes ensheathe axons to increase conduction speed, stabilize neuronal connections, and fine-tune neuron-to-neuron communication. Furthermore, pharmacological stimulation of myelination improves pain-induced cognitive deficits in mice, suggesting therapeutic potential in targeting oligodendrocytes in pain. A better understanding of how pain impacts oligodendroglia is thus crucial to better understand the pathophysiology of pain and identify new therapeutic targets.

查看原文本刊更多论文

备用神经损伤诱导小鼠少突胶质细胞密度的长期和脑区域特异性变化。

背景：越来越多的证据表明非神经元细胞在慢性疼痛的病理生理中起作用。慢性疼痛引起少突胶质细胞转录组程序的深刻改变，但疼痛对少突胶质细胞本身的影响尚不清楚。方法：雄性和雌性C57BL6/J小鼠均行神经保留损伤（SNI）。5周后采用von Frey试验评估机械超敏反应。术后6周，对小鼠进行灌注，解剖大脑，并在四个与疼痛慢性化有关的大脑区域进行少突胶质细胞前体细胞（OPC）和成熟少突胶质细胞（OL）的免疫染色：前扣带皮层（ACC）、中央杏仁核（CeA）、杏仁核基底外侧（BLA）和导水管周围灰质（PAG）。结果：经SNI治疗6周后，两性ACC和CeA的OL均有所降低。相反，在SNI处理后，两性的BLA - OL均增加。SNI对PAG-OL的影响存在性别依赖性，其中OL仅在雌性中降低。SNI不影响任何研究脑区的OPC，但女性PAG和BLA的OPC似乎比独立于SNI的男性少。结论：长期神经损伤对OL的影响在脑区和性别依赖方面存在差异。这种影响在损伤后6周可以观察到，表明慢性疼痛对少突胶质细胞的影响是持久的。另一方面，OPC非常稳定。这一发现与先前的文献一致，表明OPC即使在病理状态下也能保持稳态。意义：少突胶质细胞包裹轴突，增加传导速度，稳定神经元连接，微调神经元间通讯。此外，药物刺激髓鞘形成可改善小鼠疼痛引起的认知缺陷，提示针对疼痛的少突胶质细胞具有治疗潜力。因此，更好地了解疼痛如何影响少突胶质细胞对于更好地理解疼痛的病理生理学和确定新的治疗靶点至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Pain 医学-临床神经学

CiteScore

7.50

自引率

5.60%

发文量

163

审稿时长

4-8 weeks

期刊介绍： European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.