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Peer-reviewedCC BY-NC-ND 4.0Proceedings of the National Academy of Sciences of the United States of America

A spinoreticular pathway mediates nocifensive responses to noxious mechanical stimuli

  • Yuan Liu1,2,3
  • Qing Li1,4
  • Jun-Kai Lin1,5
  • Yifei Han1
  • Xiaoyu Yang6
  • Zining Xu1,5
  • Wanqiu Zhou1
  • Yan-Gang Sun1,4
  • Yan-Nong Dou1,4
6 affiliations
  1. 1Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
  2. 2Department of Biology, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
  3. 3Lingang Laboratory, Shanghai 200031, China
  4. 4State Key Laboratory of Brain Cognition and Brain-Inspired Intelligence Technology, Shanghai 200031, China
  5. 5University of Chinese Academy of Sciences, Beijing 100049, China
  6. 6Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai 200040, China
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Abstract

Spinal projection neurons (SPNs) relay somatosensory information to the brain, yet how molecularly defined SPN subsets transmit noxious mechanical signals to drive nocifensive behaviors remains unclear. Here, we identify Sncg-expressing SPNs (Sncg+ SPNs) that convey noxious mechanical signals through a spinoreticular ascending pathway. Using intersectional genetics, anatomical tracing, and pathway-specific manipulations in mice, we show that Sncg+ SPNs project predominantly to the parabrachial nucleus and the lateral reticular nucleus (LRN). Functional analyses reveal that Sncg+ spinoreticular pathway transmits noxious mechanical information. LRN neurons receiving Sncg+ spinal input are required for nocifensive behaviors elicited by noxious mechanical stimulation and contribute to mechanical allodynia of neuropathic pain. Monosynaptic tracing identifies local interneurons innervating Sncg+ SPNs, providing a substrate for spinal gating of ascending mechanical signals. These findings highlight a spinoreticular circuit involving the LRN that is essential for nocifensive behaviors to noxious mechanical stimuli.

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Cite

BibTeXRIS
BibTeX
@article{liu2026spinoreticular,
  title = {{A spinoreticular pathway mediates nocifensive responses to noxious mechanical stimuli}},
  author = {Yuan Liu and Qing Li and Jun-Kai Lin and Yifei Han and Xiaoyu Yang and Zining Xu and Wanqiu Zhou and Yan-Gang Sun and Yan-Nong Dou},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = aug,
  doi = {10.1073/pnas.2604642123},
  url = {https://doi.org/10.1073/pnas.2604642123},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - A spinoreticular pathway mediates nocifensive responses to noxious mechanical stimuli
AU  - Yuan Liu
AU  - Qing Li
AU  - Jun-Kai Lin
AU  - Yifei Han
AU  - Xiaoyu Yang
AU  - Zining Xu
AU  - Wanqiu Zhou
AU  - Yan-Gang Sun
AU  - Yan-Nong Dou
PY  - 2026
DA  - 2026/08/19
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2604642123
UR  - https://doi.org/10.1073/pnas.2604642123
AB  - Spinal projection neurons (SPNs) relay somatosensory information to the brain, yet how molecularly defined SPN subsets transmit noxious mechanical signals to drive nocifensive behaviors remains unclear. Here, we identify Sncg-expressing SPNs (Sncg+ SPNs) that convey noxious mechanical signals through a spinoreticular ascending pathway. Using intersectional genetics, anatomical tracing, and pathway-specific manipulations in mice, we show that Sncg+ SPNs project predominantly to the parabrachial nucleus and the lateral reticular nucleus (LRN). Functional analyses reveal that Sncg+ spinoreticular pathway transmits noxious mechanical information. LRN neurons receiving Sncg+ spinal input are required for nocifensive behaviors elicited by noxious mechanical stimulation and contribute to mechanical allodynia of neuropathic pain. Monosynaptic tracing identifies local interneurons innervating Sncg+ SPNs, providing a substrate for spinal gating of ascending mechanical signals. These findings highlight a spinoreticular circuit involving the LRN that is essential for nocifensive behaviors to noxious mechanical stimuli.
SN  - 0027-8424
SN  - 1091-6490
ER  -