Cited by 24Pain Mechanisms and TreatmentsNeuropeptides and Animal PhysiologyIon Channels and Receptors

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Transcriptional profile of spinal dynorphin-lineage interneurons in the developing mouse

Serafin, Elizabeth K., Chamessian, Alexander, Li, Jie, Zhang, Xiang, McGann, Amanda, Brewer, Chelsie L., Berta, Temugin, Baccei, Mark·2019·Pain

DOI 10.1097/j.pain.0000000000001636

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Abstract

Mounting evidence suggests that the spinal dorsal horn (SDH) contains multiple subpopulations of inhibitory interneurons that play distinct roles in somatosensory processing, as exemplified by the importance of spinal dynorphin-expressing neurons for the suppression of mechanical pain and chemical itch. Although it is clear that GABAergic transmission in the SDH undergoes significant alterations during early postnatal development, little is known about the maturation of discrete inhibitory “microcircuits” within the region. As a result, the goal of this study was to elucidate the gene expression profile of spinal dynorphin (pDyn)-lineage neurons throughout life. We isolated nuclear RNA specifically from pDyn-lineage SDH interneurons at postnatal days 7, 21, and 80 using the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) technique, followed by RNA-seq analysis. Over 650 genes were ≥2-fold enriched in adult pDyn nuclei compared with non-pDyn spinal cord nuclei, including targets with known relevance to pain such as galanin (Gal), prepronociceptin (Pnoc), and nitric oxide synthase 1 (Nos1). In addition, the gene encoding a membrane-bound guanylate cyclase, Gucy2d, was identified as a novel and highly selective marker of the pDyn population within the SDH. Differential gene expression analysis comparing pDyn nuclei across the 3 ages revealed sets of genes that were significantly upregulated (such as Cartpt, encoding cocaine- and amphetamine-regulated transcript peptide) or downregulated (including Npbwr1, encoding the receptor for neuropeptides B/W) during postnatal development. Collectively, these results provide new insight into the potential molecular mechanisms underlying the known age-dependent changes in spinal nociceptive processing and pain sensitivity.

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Authors: Serafin, E. K., Chamessian, A., Li, J., Zhang, X., McGann, A., Brewer, C. L., Berta, T., & Baccei, M.
Affiliations: University of Cincinnati Medical Center (US)
Duke Medical Center (US)
University of Cincinnati (US)
Corresponding author: Serafin, Elizabeth K.
ORCID: Serafin, Elizabeth K.
Chamessian, Alexander
Li, Jie
Zhang, Xiang
McGann, Amanda
Brewer, Chelsie L.
Berta, Temugin
Baccei, Mark
Venue: Pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2019-06-03
Volume: 160
Issue: 10
Pages: 2380-2397
ISSN: 0304-3959 (ISSN-L)
1872-6623
DOI: 10.1097/j.pain.0000000000001636
OpenAlex: W2952727025
Cited by: 24
References: 93
Citations by year: 2025: 2 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 1
FWCI: 2.23
Type: journal article
Language: en
Open access: closed
Locations: Pain (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R21NS100469)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: dorsal horn, inhibitory interneurons, postnatal development, gene expression profiling, IntAct, GUCY2D, galanin, nitric oxide synthase 1, cocaine- and amphetamine-regulated transcript, nociceptive processing, pain sensitivity
MeSH terms: Genetic Profile, Animals, Dynorphins, Female, Male, Mice, Transgenic, Transcription, Genetic, Gene Expression Regulation, Developmental, Mice, Spinal Cord Dorsal Horn

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Transcriptional profile of spinal dynorphin-lineage interneurons in the developing mouse

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