Yi Lin, Liao Tiepeng, Yuan Man, Chen Qi, Xiong Wei, Zhu Hongying
Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China.
J Biol Chem. 2025 Mar;301(3):108309. doi: 10.1016/j.jbc.2025.108309. Epub 2025 Feb 13.
Metabolic alterations in the somatosensory cortex (S1) play a crucial role in neuropathic pain development, as evidenced by magnetic resonance spectroscopy and mass spectrometry analyses of brain homogenates. However, investigating metabolic changes in specific neuronal subtypes during neuropathic pain development remains challenging. Here, utilizing a recently developed technique called single-cell mass spectrometry (SCMS), we investigated metabolomic alterations within excitatory glutamatergic neurons located in the primary S1 during various stages of neuropathic pain. Specifically, we induced neuropathic pain in mice using a spared nerve injury (SNI) model and observed activation of glutamatergic neurons in layer II/III of S1 through c-Fos staining and electrophysiology. We profiled metabolic changes and performed pathway enrichment analysis in these neurons by single-cell mass spectrometry during both acute and subchronic phases of SNI. Further analyses revealed metabolites whose alterations significantly correlated with changes in pain thresholds, as well as distinct temporal patterns of metabolite expression during pain progression. From these analyses, we identified several key metabolites (homogentisic acid, phosphatidylcholine, phosphorylcholine, and rhein) and validated their causal roles in pain modulation via pharmacological interventions. Thus, our study provides a valuable resource for elucidating the neurometabolic regulatory mechanisms underlying neuropathic pain from a single-cell perspective.
体感皮层（S1）的代谢改变在神经性疼痛的发展中起关键作用，脑匀浆的磁共振波谱和质谱分析证明了这一点。然而，在神经性疼痛发展过程中研究特定神经元亚型的代谢变化仍然具有挑战性。在这里，我们利用一种最近开发的称为单细胞质谱（SCMS）的技术，研究了在神经性疼痛的各个阶段位于初级S1的兴奋性谷氨酸能神经元内的代谢组学改变。具体而言，我们使用保留神经损伤（SNI）模型在小鼠中诱导神经性疼痛，并通过c-Fos染色和电生理学观察S1第II/III层谷氨酸能神经元的激活。我们在SNI的急性和亚慢性阶段通过单细胞质谱分析了这些神经元的代谢变化并进行了通路富集分析。进一步的分析揭示了其改变与疼痛阈值变化显著相关的代谢物，以及疼痛进展过程中代谢物表达的不同时间模式。通过这些分析，我们确定了几种关键代谢物（尿黑酸、磷脂酰胆碱、磷酸胆碱和大黄酸），并通过药理学干预验证了它们在疼痛调节中的因果作用。因此，我们的研究从单细胞角度为阐明神经性疼痛背后的神经代谢调节机制提供了有价值的资源。
