Circuit dissection of the role of somatostatin in itch and pain
Open accessAbstract
Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide.
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The Reln dorsal excitatory family comprised Excit-8, Excit-9, Excit-10, and Excit-11 and expressed markers indicative of a role in chemical itch sensation.
“The Reln dorsal, excitatory family was comprised of Excit-8, Excit-9, Excit-10, and Excit-11 and expressed markers indicative of a role in chemical itch sensation58–62.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [61]
The Pdyn dorsal inhibitory family comprised Inhib-9, Inhib-10, and Inhib-11 and expressed markers suggestive of a role in chemical itch.
“The Pdyn dorsal, inhibitory family was comprised of Inhib-9, Inhib-10, and Inhib-11 and expressed markers suggestive of a role in chemical itch52,61,73–77.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [61]
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- Authors
- Huang, J., Polgár, E., Solinski, H. J., Mishra, S. K., Tseng, P.-Y., Iwagaki, N., Boyle, K. A., Dickie, A. C., Kriegbaum, M. C., Wildner, H., Zeilhofer, H. U., Watanabe, M., Riddell, J. S., Todd, A. J., & Hoon, M. A.
- Affiliations
- National Institutes of Health (US)
- University of Glasgow (GB)
- University of Zurich (CH)
- Hokkaido University (JP)
- Corresponding author
- Todd, Andrew J.
- Hoon, Mark A.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-03-19
- Volume
- 21
- Issue
- 5
- Pages
- 707-716
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5923877
- OpenAlex
- W2796422959
- Cited by
- 257
- References
- 70
- Citations by year
- 2026: 23 · 2025: 22 · 2024: 27 · 2023: 28 · 2022: 31 · 2021: 33 · 2020: 45 · 2019: 35 · 2018: 12 · 2012: 1
- FWCI
- 21.43
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-04-19)
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Wellcome Trust (102645, 156393, 102645/Z/13/Z)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (156393)
- Medical Research Council (MR/L003430/1, MR/N003403/1)
- Biotechnology and Biological Sciences Research Council (BB/N006119/1)
- 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
- somatostatin, pruritus, pruriception, pruriceptors, dynorphin, disinhibition, spinal interneurons, primary afferents, antinociception, pain, neuropeptides, spinal cord circuitry
- MeSH terms
- Atrial Natriuretic Factor Receptor B, Animals, Dynorphins, Female, Ganglia, Spinal, Male, Mice, Inbred C57BL, Neural Pathways, Pain, Pruritus, Receptors, Purinergic, Sensory Receptor Cells, Somatostatin, Spinal Cord, Receptors, Atrial Natriuretic Factor, Receptors, Somatostatin, Mice, Optogenetics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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