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目的:本研究旨在利用空间代谢组学技术，通过坐骨神经分支损伤(SNI)模型探讨急/慢性神经病理性疼痛(NP)状态下大鼠脊髓背角内源性代谢物的变化情况，为进一步研究NP的发病机制及探寻潜在治疗靶点提供依据。方法:将雄性SD大鼠分为急性Sham组、急性SNI组、慢性Sham组和慢性SNI组，于SNI术后第1、28 d进行急/慢性疼痛行为学评估。利用质谱成像空间分辨代谢组学技术对4组大鼠脊髓背角圈选、分析，筛选差异代谢物，解析代谢通路，并进行靶向代谢物谷氨酸的定量对比研究。结果:与Sham组相比，急/慢性SNI组大鼠自发痛的频次和时间增加、机械痛阈值下降。代谢组学结果提示，与Sham组相比，急性SNI手术侧涉及苯丙氨酸、色氨酸、麦芽糖等30个差异代谢物变化，在嘌呤代谢，组氨酸代谢，丙氨酸、天冬氨酸和谷氨酸代谢等代谢通路发生改变；而慢性SNI手术侧涉及壬二酸、色氨酸等39个差异代谢物变化，在精氨酸生物合成，丙氨酸、天冬氨酸和谷氨酸代谢等代谢通路发生改变。与对侧相比，急性SNI手术侧涉及葡萄糖、麦芽糖等12个差异代谢物变化，慢性SNI手术侧涉及色氨酸、葡萄糖等19个差异代谢物变化，两组均主要在淀粉和蔗糖代谢通路发生改变。靶向代谢物检测结果表明，与Sham组相比，急性SNI组谷氨酸含量上调(P<0.05),而慢性SNI组谷氨酸含量下调(P<0.001)。结论:本研究鉴定了外周神经损伤后，急/慢性疼痛状态下脊髓背角的差异代谢物及代谢通路变化，可能与NP的发病机制密切相关。
Abstract：Objective: Using spatial metabolomics technology to investigate the changes in the endogenous metabolites in the spinal dorsal horn of rats under acute and chronic neuropathic pain(NP) induced by the spared nerve injury(SNI) model. This work is intended to provide new insights into the pathogenesis of NP and identify potential therapeutic targets. Methods: Male Sprague-Dawley(SD) rats were divided into four groups: The acute Sham group, acute SNI group, chronic Sham group, and chronic SNI group. Pain behavioral assessments for acute/chronic pain were conducted on the 1st and 28th day after SNI surgery. Spatially resolved metabolomics profiling via mass spectrometry imaging was applied to select and analyze the differential metabolites and metabolic pathways in the spinal dorsal horn, and a targeted quantitative comparison of glutamate in rats in the four groups was conducted. Results: Compared with the Sham group, the rats in the acute/chronic SNI groups exhibited increased frequency and duration of spontaneous pain, as well as a decreased mechanical pain threshold. Metabolomics results revealed that, compared with the Sham group, the ipsilateral side of acute SNI rats showed alterations in 30 differential metabolites including phenylalanine, tryptophan and maltose. Corresponding changes were observed in metabolic pathways such as purine metabolism, histidine metabolism, alanine, aspartate and glutamate metabolism. By contrast, the ipsilateral side of chronic SNI rats exhibited changes in 39 differential metabolites including azelaic acid, and tryptophan. Enriched pathways including arginine biosynthesis, alanine, aspartate and glutamate metabolism. When compared with the contralateral side, the ipsilateral spinal cord in acute SNI rats exhibited 12 differential metabolites-including glucose, maltose-while the chronic SNI group showed 19 alterations, such as tryptophan and glucose. Changes in both groups were primarily linked to starch and sucrose metabolism. Results from targeted metabolite detection demonstrated that glutamate levels were significantly upregulated in the acute SNI group compared to Sham controls, whereas a downregulation was observed in the chronic SNI group. Conclusion: This study identified the differential metabolites and changes in differential pathways in the spinal dorsal horn under acute and chronic pain states after peripheral nerve injury, suggesting that these metabolite changes are closely related to the pathological mechanism of NP.
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基本信息:
DOI：10.16557/j.cnki.1000-7547.2026.01.005
中图分类号:R741
引用信息:
[1]田小芬,于宁,孙丰润,等.神经病理性疼痛大鼠脊髓背角的空间代谢组学分析[J].神经解剖学杂志,2026,42(01):33-40.DOI:10.16557/j.cnki.1000-7547.2026.01.005.
基金信息:
国家自然科学基金(82301415); 贵州省教育厅高等学校重点实验室研究项目(黔教技[2023]015号)
2026-01-31
2026-01-31