Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice
Abstract Cortical descending modulation of sensory processing in the spinal cord has been revealed, the role of cortico-brainstem projections in sensory and motor regulation remains poorly investigated. Here, we identified two previously unappreciated subpopulations in the primary sensorimotor corte...
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| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61164-8 |
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| author | Guo-Hong Wang Xin-Yu Hou Hui-Zhu Liu Zi-Rui Zhou Su-Su Lv Lan-Xing Yi Hui Li Yu-Qiu Zhang |
| author_facet | Guo-Hong Wang Xin-Yu Hou Hui-Zhu Liu Zi-Rui Zhou Su-Su Lv Lan-Xing Yi Hui Li Yu-Qiu Zhang |
| author_sort | Guo-Hong Wang |
| collection | DOAJ |
| description | Abstract Cortical descending modulation of sensory processing in the spinal cord has been revealed, the role of cortico-brainstem projections in sensory and motor regulation remains poorly investigated. Here, we identified two previously unappreciated subpopulations in the primary sensorimotor cortex (SM1), which are anatomically and electrophysiologically distinct but functionally similar, projecting to the periaqueductal gray (PAG) and rostroventral medulla (RVM), respectively. Postsynaptic PAG glutamatergic neurons then project to the noradrenergic (NA) neurons in the locus coeruleus (LC) and 5-HT neurons in the RVM to drive spinal NA and 5-HT anti-nociception, while RVM enkephalinergic neurons that receive SM1 projections directly drive spinal opioid analgesia. Intriguingly, silencing these two SM1 subpopulations impair motor behaviors and motor-induced analgesia, but does not affect behavioral responses to cutaneous sensory stimuli. Our findings indicate that these brainstem-projecting SM1 subpopulations are crucial for cortical descending pain modulation, which could be exploited to optimize pain relief approaches. |
| format | Article |
| id | doaj-art-d1b4aa56947e49ec8d8d7598346b65af |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d1b4aa56947e49ec8d8d7598346b65af2025-08-20T03:45:31ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-61164-8Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in miceGuo-Hong Wang0Xin-Yu Hou1Hui-Zhu Liu2Zi-Rui Zhou3Su-Su Lv4Lan-Xing Yi5Hui Li6Yu-Qiu Zhang7Department of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityDepartment of Translational Neuroscience, Jing’an District Centre Hospital of Shanghai, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan UniversityAbstract Cortical descending modulation of sensory processing in the spinal cord has been revealed, the role of cortico-brainstem projections in sensory and motor regulation remains poorly investigated. Here, we identified two previously unappreciated subpopulations in the primary sensorimotor cortex (SM1), which are anatomically and electrophysiologically distinct but functionally similar, projecting to the periaqueductal gray (PAG) and rostroventral medulla (RVM), respectively. Postsynaptic PAG glutamatergic neurons then project to the noradrenergic (NA) neurons in the locus coeruleus (LC) and 5-HT neurons in the RVM to drive spinal NA and 5-HT anti-nociception, while RVM enkephalinergic neurons that receive SM1 projections directly drive spinal opioid analgesia. Intriguingly, silencing these two SM1 subpopulations impair motor behaviors and motor-induced analgesia, but does not affect behavioral responses to cutaneous sensory stimuli. Our findings indicate that these brainstem-projecting SM1 subpopulations are crucial for cortical descending pain modulation, which could be exploited to optimize pain relief approaches.https://doi.org/10.1038/s41467-025-61164-8 |
| spellingShingle | Guo-Hong Wang Xin-Yu Hou Hui-Zhu Liu Zi-Rui Zhou Su-Su Lv Lan-Xing Yi Hui Li Yu-Qiu Zhang Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice Nature Communications |
| title | Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice |
| title_full | Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice |
| title_fullStr | Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice |
| title_full_unstemmed | Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice |
| title_short | Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice |
| title_sort | descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice |
| url | https://doi.org/10.1038/s41467-025-61164-8 |
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