ArticleCell reports2024
Spatial, transcriptomic, and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition.
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Who cites it
20 citing papers in PubMed.
- Targeting Spinal Dorsal Horn Sensitisation in Chronic Pain: Mechanisms and Translational Strategies.Neuroscience bulletin · 2026Review
- Article
- METTL3-mediated m6A modification of circMtmr7 contributes to paclitaxel-induced peripheral neuropathy in the dorsal horn.The Journal of physiology · 2026Article
- Lanthionine synthetase C-like protein 1 (LanCL1): a therapeutic target for neuropathic pain.Pain · 2026Article
- Deep Cellular and Spatial Profiling of the Mouse Spinal Cord Reveals Sex-Specific Neuron Types and the Ascending Projection Neuron Repertoire.bioRxiv : the preprint server for biology · 2026Article
- A Novel Approach to Neuropathic Pain Treatment: Lactylation Targeting Microglia.Molecular neurobiology · 2026Review
- A consensus spinal cord cell type atlas across mouse, macaque, and human.bioRxiv : the preprint server for biology · 2026Article
- Spatial transcriptomics reveals organizational properties of mouse spinal cord and alterations in neuropathic pain.bioRxiv : the preprint server for biology · 2026Article
- Ontogeny of the spinal cord dorsal horn.Science (New York, N.Y.) · 2026Article
- Processing and sectioning of organ donor spinal cord tissue for electrophysiology on acute human spinal cord slices.Brain communications · 2026Article
- The cell-type-specific genetic architecture of chronic pain in brain and dorsal root ganglia.The Journal of clinical investigation · 2025Article
- Harnessing theta-gamma coupled brainwaves using ultrasound for spinal astrocyte revitalization and sustained neuropathic pain relief in mice.Nature communications · 2025Article
- Not Just Neurons: Pain Is Orchestrated in Partnership with Many Non-neuronal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- A molecular map of the human spinal dorsal and ventral horn defines arrangement of neuronal types and glial sex differences.bioRxiv : the preprint server for biology · 2025Article
- Early Life Injury Alters Spinal Astrocyte Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Innovations in spinal cord cell type heterogeneity across vertebrate evolution.bioRxiv : the preprint server for biology · 2025Article
- A multi-omic atlas of human autonomic and sensory ganglia implicates cell types in peripheral neuropathies.bioRxiv : the preprint server for biology · 2025Article
- Etiological basis for chronic pain genetic variation in brain and dorsal root ganglia cell types.medRxiv : the preprint server for health sciences · 2025Article
- Combining Machine Learning and Multiplexed,bioRxiv : the preprint server for biology · 2025Article
- How microglia contribute to the induction and maintenance of neuropathic pain.Nature reviews. Neuroscience · 2025Review
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Authors and funding
25 authors.
Cynthia M ArokiarajDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Michael J LeoneDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Michael KleymanDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Alexander ChamessianDepartment of Anesthesiology, Duke University Medical Center, Durham, NC 27708, USA; Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Myung-Chul NohDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
BaDoi N PhanDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Bettega C LopesDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Kelly A CorriganDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Vijay Kiran CherupallyDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Deepika YeramosuDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Michael E FranusichDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Riya PodderDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Sumitra LeleDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Stephanie ShiersDepartment of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA.
Byungsoo KangDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Meaghan M KennedyDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Viola ChenDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Ziheng ChenDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Department of Biological Sciences, Mellon College of Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Hansruedi MathysDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Richard P DumDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
David A LewisDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Yawar QadriDepartment of Anesthesiology, Emory University, Atlanta, GA 30038, USA.
Theodore J PriceDepartment of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA.
Andreas R PfenningDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Electronic address: apfenning@cmu.edu.
Rebecca P SealDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address: rpseal@pitt.edu.
Funding
Schizophrenia and synaptic pruning: Circuit specificity and functional consequencesR01MH051234 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 1995 to 2020
$8.5MMedical Scientist Training Program Training GrantT32GM145449 · NIGMS · DUKE UNIVERSITY · PI Christopher D Kontos · 2022 to 2026
$6.6MAnatomic, Physiologic and Transcriptomic Mechanisms of Neuropathic Pain in Human DRGR01NS111929 · NINDS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DOUGHERTY, PATRICK M, PRICE, THEODORE J. · 2020 to 2024
$3.4MTraining in Mechanisms and Clinical Presentation of PainT32NS073548 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jami Lynn Saloman, BRADLEY K. TAYLOR · 2012 to 2026
$3.1MDorsal horn circuits for mechanical allodyniaR01NS107364 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SEAL, REBECCA P · 2019 to 2022
$2.1MCentral Circuits for Mechanical PainR56NS104964 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SEAL, REBECCA P · 2018 to 2018
$543kCell-type specific molecular and functional analyses to target dorsal horn pain circuitry in mice and non-human primatesR56NS133364 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PFENNING, ANDREAS ROBERT, SEAL, REBECCA P · 2023 to 2023
$499kMolecular and functional organization of the dorsal horn in mouse and non-human primateR21NS109792 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SEAL, REBECCA P · 2018 to 2019
$413kIntegrating primate-rodent cell types and epigenomics to identify conservation in substance addictionF30DA053020 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PHAN, BADOI NGUYEN · 2021 to 2024
$204kStudy of the Cholesystokinin (CCK) Molecular Subsets in the Mouse and Macaque Dorsal HornF31NS111791 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AROKIARAJ, CYNTHIA MARY · 2019 to 2020
$91kIdentifying and targeting neural subpopulations of the spinal cord that mediate chronic pain via cell-type-specific cis-regulatory elementsF31NS134318 · NINDS · CARNEGIE-MELLON UNIVERSITY · PI LEONE, MICHAEL · 2024 to 2025
$75kNIDA NIH HHS F30 DA053020NIGMS NIH HHS T32 GM145449NIMH NIH HHS R01 MH051234NINDS NIH HHS F31 NS111791NINDS NIH HHS F31 NS134318NINDS NIH HHS R01 NS107364NINDS NIH HHS R01 NS111929NINDS NIH HHS R21 NS109792NINDS NIH HHS R56 NS104964NINDS NIH HHS R56 NS133364NINDS NIH HHS T32 NS073548
Abstract
Key mechanisms underlying chronic pain occur within the dorsal horn. Genome-wide association studies (GWASs) have identified genetic variants predisposed to chronic pain. However, most of these variants lie within regulatory non-coding regions that have not been linked to spinal cord biology. Here, we take a multi-species approach to determine whether chronic pain variants impact the regulatory genomics of dorsal horn neurons. First, we generate a large rhesus macaque single-nucleus RNA sequencing (snRNA-seq) atlas and integrate it with available human and mouse datasets to produce a single unified, species-conserved atlas of neuron subtypes. Cellular-resolution spatial transcriptomics in mouse shows the precise laminar location of these neuron subtypes, consistent with our analysis of neuron-subtype-selective markers in macaque. Using this cross-species framework, we generate a mouse single-nucleus open chromatin atlas of regulatory elements that shows strong and selective relationships between the neuron-subtype-specific chromatin regions and variants from major chronic pain GWASs.
Indexed as
Chronic PainEpigenomicsGenetic Predisposition to DiseaseMacaca mulattaPosterior Horn CellsTranscriptomeAnimalsChromatinGenome-Wide Association StudyHumansMiceChromatincell typeschronic painCP: NeuroscienceGWAShumanmousemultiplexed in situ hybridizationrhesus macaquesingle-nucleus ATAC-seqsingle-nucleus RNA sequencingspatial transcriptomicsspinal cordvariants
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