Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China; Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China
Yilong Ren
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China; Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China
Lijuan Zhao
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China; Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China
Jingwei Zhao
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China; Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China
Shuai Yin
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China; Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China
Haofei Ni
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China; Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China
Rongrong Zhu
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China
Liming Cheng
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China; Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China; Clinical Center for Brain and Spinal Cord Research, Tongji University, Shanghai, China
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China; Division of Spine, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China
Astrocytes derive from different lineages and play a critical role in neuropathic pain after spinal cord injury (SCI). Whether selectively eliminating these main origins of astrocytes in lumbar enlargement could attenuate SCI-induced neuropathic pain remains unclear. Through transgenic mice injected with an adeno-associated virus vector and diphtheria toxin, astrocytes in lumbar enlargement were lineage traced, targeted, and selectively eliminated. Pain-related behaviors were measured with an electronic von Frey apparatus and a cold/hot plate after SCI. RNA sequencing, bioinformatics analysis, molecular experiment, and immunohistochemistry were used to explore the potential mechanisms after astrocyte elimination. Lineage tracing revealed that the resident astrocytes but not ependymal cells were the main origins of astrocytes-induced neuropathic pain. SCI-induced mice to obtain significant pain symptoms and astrocyte activation in lumbar enlargement. Selective resident astrocyte elimination in lumbar enlargement could attenuate neuropathic pain and activate microglia. Interestingly, the type I interferons (IFNs) signal was significantly activated after astrocytes elimination, and the most activated Gene Ontology terms and pathways were associated with the type I IFNs signal which was mainly activated in microglia and further verified in vitro and in vivo. Furthermore, different concentrations of interferon and Stimulator of interferon genes (STING) agonist could activate the type I IFNs signal in microglia. These results elucidate that selectively eliminating resident astrocytes attenuated neuropathic pain associated with type I IFNs signal activation in microglia. Targeting type I IFNs signals is proven to be an effective strategy for neuropathic pain treatment after SCI.
