An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord
Abstract Peripheral nerve injury (PNI)-induced neuropathic pain (NP) is a severe disease with high prevalence in clinics. Gene reprogramming and tissue remodeling in the dorsal root ganglia (DRG) and spinal cord (SC) drive the development and maintenance of neuropathic pain (NP). However, our unders...
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2025-01-01
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Online Access: | https://doi.org/10.1038/s42003-025-07506-0 |
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author | Fu-Lu Dong Lina Yu Pei-Da Feng Jin-Xuan Ren Xue-Hui Bai Jia-Qi Lin De-Li Cao Yu-Tao Deng Yan Zhang Hui-Hui Shen Hao Gong Wen-Xing Sun Dong-Qiu Chi Yixiao Mei Longfei Ma Ming-Zhe Yin Meng-Na Li Peng-Fei Zhang Nan Hu Bing-Lin Zhou Ying Liu Xuan-Jie Zheng Yi-Fan Chen Da Zhong Yuan-Xiang Tao Min Yan Bao-Chun Jiang |
author_facet | Fu-Lu Dong Lina Yu Pei-Da Feng Jin-Xuan Ren Xue-Hui Bai Jia-Qi Lin De-Li Cao Yu-Tao Deng Yan Zhang Hui-Hui Shen Hao Gong Wen-Xing Sun Dong-Qiu Chi Yixiao Mei Longfei Ma Ming-Zhe Yin Meng-Na Li Peng-Fei Zhang Nan Hu Bing-Lin Zhou Ying Liu Xuan-Jie Zheng Yi-Fan Chen Da Zhong Yuan-Xiang Tao Min Yan Bao-Chun Jiang |
author_sort | Fu-Lu Dong |
collection | DOAJ |
description | Abstract Peripheral nerve injury (PNI)-induced neuropathic pain (NP) is a severe disease with high prevalence in clinics. Gene reprogramming and tissue remodeling in the dorsal root ganglia (DRG) and spinal cord (SC) drive the development and maintenance of neuropathic pain (NP). However, our understanding of the NP-associated spatial molecular processing landscape of SC and the non-synaptic interactions between DRG neurons and SC cells remains limited. We here integrate spatial transcriptomics (ST) with single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (bulk RNA-seq) to characterize regional pathological heterogeneity of the SC under NP conditions. First, the SC of NP mice manifests unique spatial atlases of genes, cell populations, cell-cell cross-talks, signaling pathways, and transcriptional regulatory networks compared to sham mice. We further report that injured DRG sensory neurons and the corresponding ventral horn of the SC show similar expression patterns after PNI. In addition, for the first time, we systematically exhibit “cross-talk omics” between the DRG neurons and SC dorsal horn neurons and glial cells, indicating an altered communication profile under NP conditions. Together, our findings decode the spatial and cellular heterogeneity of molecular pathological mechanisms underlying NP, providing a foundation for designing therapeutic targets for this disorder. |
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language | English |
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spelling | doaj-art-8e2277d3c24e4e63a59e44fd40c217fe2025-01-19T12:35:32ZengNature PortfolioCommunications Biology2399-36422025-01-018112110.1038/s42003-025-07506-0An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cordFu-Lu Dong0Lina Yu1Pei-Da Feng2Jin-Xuan Ren3Xue-Hui Bai4Jia-Qi Lin5De-Li Cao6Yu-Tao Deng7Yan Zhang8Hui-Hui Shen9Hao Gong10Wen-Xing Sun11Dong-Qiu Chi12Yixiao Mei13Longfei Ma14Ming-Zhe Yin15Meng-Na Li16Peng-Fei Zhang17Nan Hu18Bing-Lin Zhou19Ying Liu20Xuan-Jie Zheng21Yi-Fan Chen22Da Zhong23Yuan-Xiang Tao24Min Yan25Bao-Chun Jiang26Department of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, Medical School, Nantong UniversityDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineInstitute of Pain Medicine and Special Environmental Medicine, Nantong UniversityDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineInstitute of Pain Medicine and Special Environmental Medicine, Nantong UniversityDepartment of Nutrition and Food Hygiene, School of Public Health, Nantong UniversityMedical Service Center, Nantong UniversityDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineInstitute of Pain Medicine and Special Environmental Medicine, Nantong UniversityInstitute of Pain Medicine and Special Environmental Medicine, Nantong UniversityInstitute of Pain Medicine and Special Environmental Medicine, Nantong UniversityDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, Medical School, Nantong UniversityDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New JerseyDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of MedicineAbstract Peripheral nerve injury (PNI)-induced neuropathic pain (NP) is a severe disease with high prevalence in clinics. Gene reprogramming and tissue remodeling in the dorsal root ganglia (DRG) and spinal cord (SC) drive the development and maintenance of neuropathic pain (NP). However, our understanding of the NP-associated spatial molecular processing landscape of SC and the non-synaptic interactions between DRG neurons and SC cells remains limited. We here integrate spatial transcriptomics (ST) with single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (bulk RNA-seq) to characterize regional pathological heterogeneity of the SC under NP conditions. First, the SC of NP mice manifests unique spatial atlases of genes, cell populations, cell-cell cross-talks, signaling pathways, and transcriptional regulatory networks compared to sham mice. We further report that injured DRG sensory neurons and the corresponding ventral horn of the SC show similar expression patterns after PNI. In addition, for the first time, we systematically exhibit “cross-talk omics” between the DRG neurons and SC dorsal horn neurons and glial cells, indicating an altered communication profile under NP conditions. Together, our findings decode the spatial and cellular heterogeneity of molecular pathological mechanisms underlying NP, providing a foundation for designing therapeutic targets for this disorder.https://doi.org/10.1038/s42003-025-07506-0 |
spellingShingle | Fu-Lu Dong Lina Yu Pei-Da Feng Jin-Xuan Ren Xue-Hui Bai Jia-Qi Lin De-Li Cao Yu-Tao Deng Yan Zhang Hui-Hui Shen Hao Gong Wen-Xing Sun Dong-Qiu Chi Yixiao Mei Longfei Ma Ming-Zhe Yin Meng-Na Li Peng-Fei Zhang Nan Hu Bing-Lin Zhou Ying Liu Xuan-Jie Zheng Yi-Fan Chen Da Zhong Yuan-Xiang Tao Min Yan Bao-Chun Jiang An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord Communications Biology |
title | An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord |
title_full | An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord |
title_fullStr | An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord |
title_full_unstemmed | An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord |
title_short | An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord |
title_sort | atlas of neuropathic pain associated molecular pathological characteristics in the mouse spinal cord |
url | https://doi.org/10.1038/s42003-025-07506-0 |
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