Cited by 17Pain Mechanisms and TreatmentsDermatology and Skin DiseasesIon Channels and Receptors

Spinal Inhibitory Ptf1a-Derived Neurons Prevent Self-Generated Itch

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Escalante, Augusto, Klein, Rüdiger·2020·Cell Reports

Published version of a preprint

Abstract

Chronic itch represents an incapacitating burden on patients suffering from a spectrum of diseases. Despite recent advances in our understanding of the cells and circuits implicated in the processing of itch information, chronic itch often presents itself without an apparent cause. Here, we identify a spinal subpopulation of inhibitory neurons defined by the expression of Ptf1a, involved in gating mechanosensory information self-generated during movement. These neurons receive tactile and motor input and establish presynaptic inhibitory contacts on mechanosensory afferents. Loss of Ptf1a neurons leads to increased hairy skin sensitivity and chronic itch, partially mediated by the classic itch pathway involving gastrin-releasing peptide receptor (GRPR) spinal neurons. Conversely, chemogenetic activation of GRPR neurons elicits itch, which is suppressed by concomitant activation of Ptf1a neurons. These findings shed light on the circuit mechanisms implicated in chronic itch and open novel targets for therapy developments.

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Crossref · 10.1016/j.celrep.2020.108422

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  • A subset of cells from the dorsal dI4.6/dI6 lineages contributed to most ventral inhibitory populations.

    “A subset of cells from the dorsal dI4.6/dI6 lineages contributed to most ventral inhibitory populations, which was unexpected though there have been reports of scattered dI4 Ptf1a-derived cells in the embryonic and perinatal ventral horn103,104, and the very small dI6 population is known to be ventrally located105–107.”

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Authors
Escalante, A., & Klein, R.
Affiliations
Max Planck Institute of Neurobiology (DE)
Corresponding author
  • Escalante, Augusto
  • Klein, Rüdiger
Venue
Cell Reports
Publisher
Elsevier BV
Published
2020-11
Volume
33
Issue
8
Pages
108422
ISSN
2211-1247 (ISSN-L)
OpenAlex
W3107880009
Cited by
17
References
100
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 1
FWCI
1.80
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-nd)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
  • Max-Planck-Gesellschaft
  • “la Caixa” Foundation
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords
chronic pruritus, Ptf1a, gastrin-releasing peptide receptor, tactile sensitivity, chemogenetic activation
MeSH terms
Animals, DNA-Binding Proteins, Humans, Neurons, Pruritus, Transcription Factors, Mice

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