ArticleThe Journal of clinical investigation2025
The cell-type-specific genetic architecture of chronic pain in brain and dorsal root ganglia.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Single-cell and single-nucleus transcriptomics of the dorsal root ganglion in neuropathic pain: cell-state remodeling and translational prospects.Journal of translational medicine · 2026Review
- Advances in the Comprehensive Tree Shrew Brain Atlas.Biomolecules · 2026Review
- Investigating genetic overlap of multidimensional pain and suicidal behaviors in >2 million individuals.Research square · 2026Article
- Mapping the Extended Pain Pathway: Human Genetic and Multi-Omic Strategies for Next-Generation Analgesics.International journal of molecular sciences · 2026Review
- New insight into RNA biomarkers in neuropathic pain: a clinician-neuroscientist roadmap to translational testing and treatment monitoring a clinical review.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- A high-resolution genomic roadmap for chronic pain converges on glutamatergic neurons and C-fibers.The Journal of clinical investigation · 2025Article
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17 authors.
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Abstract
Chronic pain is a complex clinical problem comprising multiple conditions that may share a common genetic profile. GWAS have identified many risk loci whose cell-type context remains unclear. Here, we integrated GWAS data on chronic pain with single-cell RNA-Seq (scRNA-Seq) data from human brain and dorsal root ganglia (hDRG) and single-cell chromatin accessibility data from human brain and mouse dorsal horn. Pain-associated variants were enriched in glutamatergic neurons, mainly in the prefrontal cortex, hippocampal CA1-3, and amygdala. In hDRG, the hPEP.TRPV1/A1.2 neuronal subtype showed robust enrichment. Chromatin accessibility analyses revealed variant enrichment in excitatory and inhibitory neocortical neurons in the brain and in midventral neurons and oligodendrocyte precursor cells in the mouse dorsal horn. Gene-level heritability in the brain highlighted roles for kinase activity, GABAergic synapses, axon guidance, and neuron projection development. In hDRG, implicated genes were related to glutamatergic signaling and neuronal projection. In cervical DRG of patients with acute versus chronic pain, scRNA-Seq data from neuronal or non-neuronal cells were enriched for chronic pain-associated genes (e.g., EFNB2, GABBR1, NCAM1, SCN11A). This cell-type-specific genetic architecture of chronic pain across central and PNS circuits provides a foundation for targeted translational research.
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