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Spinal somatostatin-positive interneurons transmit chemical itch
Abstract
Recent studies have made significant progress in identifying distinct populations of peripheral neurons involved in itch transmission, whereas the cellular identity of spinal interneurons that contribute to itch processing is still a debate. Combining genetic and pharmacological ablation of spinal excitatory neuronal subtypes and behavioral assays, we demonstrate that spinal somatostatin-positive (SOM+) excitatory interneurons transmit pruritic sensation. We found that the ablation of spinal SOM+/Lbx1+ (SOM Lbx1) neurons caused significant attenuation of scratching responses evoked by various chemical pruritogens (chemical itch). In an attempt to identify substrates of spinal itch neural circuit, we observed that spinal SOM+ neurons partially overlapped with neurons expressing natriuretic peptide receptor A (Npra), the receptor of peripheral itch transmitter B-type natriuretic peptide. Spinal SOM+ neurons, however, did not show any overlap with itch transmission neurons expressing gastrin-releasing peptide receptor in the dorsal spinal cord, and the gastrin-releasing peptide–triggered scratching responses were intact after ablating spinal SOM+ neurons. Dual ablation of SOM Lbx1 and Npra+ neurons in the spinal cord reduced chemical itch responses to a greater extent than ablation of SOM Lbx1 or Npra+ neurons alone, suggesting the existence of parallel spinal pathways transmitting chemical itch. Furthermore, we showed that SOM peptide modulated itch processing through disinhibition of somatostatin receptor 2A–positive inhibitory interneuron. Together, our findings reveal a novel spinal mechanism for sensory encoding of itch perception.
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“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 [60]
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Metadata
- Authors
- Fatima, M., Ren, X., Pan, H., Slade, H. F. E., Asmar, A. J., Xiong, C. M., Shi, A., Xiong, A. E., Wang, L., & Duan, B.
- Affiliations
- University of Michigan (US)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Duan, Bo
- Venue
- Pain
- Published
- 2019-01-24
- Volume
- 160
- Issue
- 5
- Pages
- 1166-1174
- ISSN
- 0304-3959 (ISSN-L)
- 1872-6623
- OpenAlex
- W2913470140
- Cited by
- 41
- References
- 54
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 3 · 2020: 2 · 2019: 4
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS109170)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- pruritus, scratching behavior, natriuretic peptide receptor A, brain natriuretic peptide, gastrin-releasing peptide receptor, somatostatin receptor 2A, inhibitory interneurons
- MeSH terms
- Action Potentials, Animals, Chloroquine, p-Methoxy-N-methylphenethylamine, Disease Models, Animal, Interneurons, Luminescent Proteins, Lysine, Mice, Inbred C57BL, Mice, Transgenic, Muscle Proteins, Nitrobenzoates, Pruritus, Somatostatin, Spinal Cord, Proto-Oncogene Proteins c-fos, tau Proteins, Patch-Clamp Techniques, Angiogenesis Inhibitors, Mice, In Vitro Techniques
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