Cited by 108Pain Mechanisms and TreatmentsIon Channels and ReceptorsDermatology and Skin Diseases

Spinal Neuropeptide Y1 Receptor-Expressing Neurons Form an Essential Excitatory Pathway for Mechanical Itch

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Acton, David, Ren, Xiangyu, Di Costanzo, Stefania, Dalet, Antoine, Bourane, Steeve, Bertocchi, Ilaria, Eva, Carola, Goulding, Martyn·2019·Cell Reports

Abstract

Acute itch can be generated by either chemical or mechanical stimuli, which activate separate pathways in the periphery and spinal cord. While substantial progress has been made in mapping the transmission pathway for chemical itch, the central pathway for mechanical itch remains obscure. Using complementary genetic and pharmacological manipulations, we show that excitatory neurons marked by the expression of the neuropeptide Y1 receptor (Y1 Cre neurons) form an essential pathway in the dorsal spinal cord for the transmission of mechanical but not chemical itch. Ablating or silencing the Y1 Cre neurons abrogates mechanical itch, while chemogenetic activation induces scratching. Moreover, using Y1 conditional knockout mice, we demonstrate that endogenous neuropeptide Y (NPY) acts via dorsal-horn Y1-expressing neurons to suppress light punctate touch and mechanical itch stimuli. NPY-Y1 signaling thus regulates the transmission of innocuous tactile information by establishing biologically relevant thresholds for touch discrimination and mechanical itch reflexes.

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Crossref · 10.1016/j.celrep.2019.06.033

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  • The Prkcg dorsal excitatory family comprised Excit-3 and Excit-4 and likely corresponded to neurons involved in light static touch and allodynic pain in pathological situations.

    “The Prkcg dorsal, excitatory family was comprised of Excit-3 and Excit-4 and likely corresponded to neurons involved in light static touch and allodynic pain in pathological situations46,48–56.”

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Authors
Acton, D., Ren, X., Di Costanzo, S., Dalet, A., Bourane, S., Bertocchi, I., Eva, C., & Goulding, M.
Affiliations
  • Salk Institute for Biological Studies (US)
  • Neuroscience Institute Cavalieri Ottolenghi (IT)
Corresponding author
Goulding, Martyn
Venue
Cell Reports
Publisher
Elsevier BV
Published
2019-07
Volume
28
Issue
3
Pages
625-639.e6
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2961169698
Cited by
108
References
97
Citations by year
2026: 13 · 2025: 12 · 2024: 17 · 2023: 18 · 2022: 13 · 2021: 12 · 2020: 17 · 2019: 6
FWCI
8.20
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Keywords
Y1 receptor, neuropeptide Y, dorsal horn neurons, spinal cord, scratching behavior, nociception, chemogenetic activation, neuronal ablation
MeSH terms
Animals, Capsaicin, Clozapine, Interneurons, Mechanoreceptors, Neuropeptide Y, Reflex, Spinal Cord, Stimulation, Chemical, Receptors, Neuropeptide Y, Mice, Knockout, Sensory System Agents, Posterior Horn Cells, Mice

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