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在小鼠脊髓中编码伤害性机械性和热痛觉的神经集合。

Neural ensembles that encode nocifensive mechanical and heat pain in mouse spinal cord.

作者信息

Zhang Ming-Dong, Kupari Jussi, Su Jie, Magnusson Kajsa A, Hu Yizhou, Calvo-Enrique Laura, Usoskin Dmitry, Albisetti Gioele W, Ceder Mikaela M, Henriksson Katharina, Leavitt Andrew D, Zeilhofer Hanns Ulrich, Hökfelt Tomas, Lagerström Malin C, Ernfors Patrik

机构信息

Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, Stockholm, Sweden.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

出版信息

Nat Neurosci. 2025 May;28(5):1012-1023. doi: 10.1038/s41593-025-01921-6. Epub 2025 Mar 24.

DOI:10.1038/s41593-025-01921-6
PMID:40128392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12081300/
Abstract

Acute pain is an unpleasant experience caused by noxious stimuli. How the spinal neural circuits attribute differences in quality of noxious information remains unknown. By means of genetic capturing, activity manipulation and single-cell RNA sequencing, we identified distinct neural ensembles in the adult mouse spinal cord encoding mechanical and heat pain. Reactivation or silencing of these ensembles potentiated or stopped, respectively, paw shaking, lifting and licking within but not across the stimuli modalities. Within ensembles, polymodal Gal inhibitory neurons with monosynaptic contacts to A-fiber sensory neurons gated pain transmission independent of modality. Peripheral nerve injury led to inferred microglia-driven inflammation and an ensemble transition with decreased recruitment of Gal inhibitory neurons and increased excitatory drive. Forced activation of Gal neurons reversed hypersensitivity associated with neuropathy. Our results reveal the existence of a spinal representation that forms the neural basis of the discriminative and defensive qualities of acute pain, and these neurons are under the control of a shared feed-forward inhibition.

摘要

急性疼痛是由有害刺激引起的一种不愉快体验。脊髓神经回路如何区分有害信息的质量差异仍不清楚。通过基因捕获、活动操纵和单细胞RNA测序，我们在成年小鼠脊髓中鉴定出编码机械性疼痛和热痛的不同神经集群。这些集群的重新激活或沉默分别增强或停止了爪部在刺激模式内而非跨刺激模式的抖动、抬起和舔舐。在集群内，与A纤维感觉神经元有单突触联系的多模式γ-氨基丁酸（Gal）抑制性神经元不依赖于模式地调节疼痛传递。外周神经损伤导致推测的小胶质细胞驱动的炎症以及一个集群转变，即γ-氨基丁酸抑制性神经元的募集减少和兴奋性驱动增加。γ-氨基丁酸神经元的强制激活逆转了与神经病变相关的超敏反应。我们的结果揭示了一种脊髓表征的存在，它构成了急性疼痛的辨别性和防御性特质的神经基础，并且这些神经元受共同的前馈抑制控制。

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