斯坦福大学陈晓科小组近日取得一项新成果。经过不懈努力，他们的研究开发出了解构驱动慢性疼痛的脊髓-脑-脊髓回路。相关论文发表在2026年4月1日出版的《自然》杂志上。

在这里，该研究团队报道了一个从脊髓延伸到丘脑后外侧腹侧和丘脑后复合体的回路，进入初级体感皮层，并通过外侧上丘返回脊髓，后者又连接到表达μ-阿片受体的RVMSC神经元。沉默多突触回路中的任何节点对健康小鼠的伤害感觉影响很小，但可以消除机械性超敏反应并恢复炎症性和神经性疼痛的无主题模型中的正常伤害反应阈值。在健康小鼠中，该回路中每个节点的重复（但不是急性）激活足以消除慢性机械超敏反应。他们的发现揭示了一个连接上升和下降通路的脊髓-脑-脊髓回路回路，并特别导致慢性机械性疼痛。这可能使识别治疗慢性疼痛的细胞靶标成为可能。

据悉，周围的组织炎症或神经损伤可引起慢性疼痛。尽管在吻侧腹内侧髓质（RVMSC神经元）的脊髓投射神经元可以促进疼痛的慢性化，但外周损伤信号驱动这些神经元的途径尚不清楚。

附：英文原文

Title: Deconstruction of a spino-brain–spinal cord circuit that drives chronic pain

Author: Wang, Qian, Lee, Joo Han, Nachtrab, Gregory, Yuan, Yuan, Yuan, Lei, Qi, Wei, Mohr, Manuel A., Xiong, Jing, Horowitz, Mark A., Chen, Xiaoke

Issue&Volume: 2026-04-01

Abstract: Tissue inflammation or nerve injury at the periphery can cause chronic pain. Although the spinal-cord-projecting neurons in the rostral ventromedial medulla (RVMSC neurons) can promote pain chronification1,2,3,4, the pathway by which peripheral injury signals drive these neurons is poorly understood1,2,3,5. Here we report a circuit loop that extends from the spinal cord to the ventral posterolateral thalamus and posterior complex of the thalamus, proceeds to the primary somatosensory cortex and returns to the spinal cord via the lateral superior colliculus, which in turn connects to μ-opioid-receptor-expressing RVMSC neurons. Silencing any node along this multisynaptic circuit has minimal effects on nociception in healthy mice, but can eliminate mechanical hypersensitization and restore normal nociceptive response thresholds in mouse models of inflammatory and neuropathic pain. In healthy mice, repetitive—but not acute—activation of each node in this circuit is sufficient to cause robust chronic mechanical hypersensitization. Our findings reveal a spino-brain–spinal cord circuit loop that links ascending and descending pathways and specifically drives chronic mechanical pain. This could enable the identification of cellular targets for treating chronic pain.

DOI: 10.1038/s41586-026-10296-y

Source: https://www.nature.com/articles/s41586-026-10296-y