Patrik Karolinska InstitutetErnfors研究组在研究中取得进展。他们报道了小鼠脊髓中编码有害机械痛和热痛的神经系统。这一研究成果发表在2025年3月24日出版的国际学术期刊《自然—神经科学》上。

通过基因捕获、活动操作和单细胞RNA测序，研究人员在成人无主脊髓中发现了编码机械痛和热痛的不同神经系统。这些组合的重新激活或沉默分别增强或停止了在刺激模式内而不是跨刺激模式的爪摇、举和舔。在整体中，与A纤维感觉神经元单突触接触的多模态Gal⁺抑制性神经元独立于模态控制疼痛传递。周围神经损伤导致推断小胶质细胞驱动的炎症和Gal⁺抑制性神经元募集减少和兴奋性驱动增加的整体转变。Gal⁺神经元的强制激活逆转了与神经病变相关的超敏反应。他们的研究结果揭示了脊髓表征的存在，它构成了急性疼痛的鉴别和防御特性的神经基础，这些神经元受到共同前馈抑制的控制。

据了解，急性疼痛是由刺激性刺激引起的一种不愉快的体验。脊髓神经回路是如何将一氧化氮信息的质量差异归为不同的仍是未知的。

附：英文原文

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

Author: 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, Hkfelt, Tomas, Lagerstrm, Malin C., Ernfors, Patrik

Issue&Volume: 2025-03-24

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.

DOI: 10.1038/s41593-025-01921-6

Source: https://www.nature.com/articles/s41593-025-01921-6