Spinal Neuropeptide Y1 Receptor-Expressing Neurons Form an Essential Excitatory Pathway for Mechanical Itch
Open accessAbstract
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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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.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [49]
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Self-citationPain Inhibits GRPR Neurons via GABAergic Signaling in the Spinal Cord
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Advances in Understanding the Initial Steps of Pruritoceptive Itch: How the Itch Hits the Switch
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Self-citationMolecular Aspects of Pruritus Pathogenesis in Psoriasis
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Somatostatin Neurons from Periaqueductal Gray to Medulla Facilitate Neuropathic Pain in Male Mice
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Spinal Inhibitory Ptf1a-Derived Neurons Prevent Self-Generated Itch
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Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1
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The Delta-Opioid Receptor Bidirectionally Modulates Itch
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Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signallingPreprint
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A specialized population of hair afferents dedicated to transmitting mechanical itch
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Functional Populations Among Interneurons in the Dorsal Horn
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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)
- PMC
- PMC6709688
- 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
- gold
- doi.org
- Licence
- 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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