Identification of Early RET+ Deep Dorsal Spinal Cord Interneurons in Gating Pain
Open accessAbstract
The gate control theory (GCT) of pain proposes that pain- and touch-sensing neurons antagonize each other through spinal cord dorsal horn (DH) gating neurons. However, the exact neural circuits underlying the GCT remain largely elusive. Here, we identified a new population of deep layer DH (dDH) inhibitory interneurons that express the receptor tyrosine kinase Ret neonatally. These early RET+ dDH neurons receive excitatory as well as polysynaptic inhibitory inputs from touch- and/or pain-sensing afferents. In addition, they negatively regulate DH pain and touch pathways through both pre- and postsynaptic inhibition. Finally, specific ablation of early RET+ dDH neurons increases basal and chronic pain, whereas their acute activation reduces basal pain perception and relieves inflammatory and neuropathic pain. Taken together, our findings uncover a novel spinal circuit that mediates crosstalk between touch and pain pathways and suggest that some early RET+ dDH neurons could function as pain "gating" neurons.
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The Rorb and Adamts5 dorsal inhibitory family comprised Inhib-1, Inhib-2, Inhib-3, Inhib-4, and Inhib-5, with markers of neurons involved in dampening of dynamic touch.
“The Rorb and Adamts5 dorsal, the inhibitory family was comprised of Inhib-1, Inhib-2, Inhib-3, Inhib-4, and Inhib-5, with markers of neurons involved in the dampening of dynamic touch48,68,69.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [68]
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- Authors
- Cui, L., Miao, X., Liang, L., Abdus-Saboor, I., Olson, W., Fleming, M. S., Ma, M., Tao, Y.-X., & Luo, W.
- Affiliations
- University of Pennsylvania (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Tao, Yuan-Xiang
- Luo, Wenqin
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 91
- Issue
- 5
- Pages
- 1137-1153
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5017914
- OpenAlex
- W2511651422
- Cited by
- 100
- References
- 46
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 6 · 2023: 11 · 2022: 11 · 2021: 13 · 2020: 8 · 2019: 16 · 2018: 13 · 2017: 12 · 2016: 2
- FWCI
- 11.53
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-09-21)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- Harvard University
- Washington University in St. Louis
- National Heart, Lung, and Blood Institute (U01HL117684)
- National Institute on Drug Abuse (R01DA033390)
- National Institute of General Medical Sciences (K12GM081259)
- National Institute of Neurological Disorders and Stroke (R01NS072206, F31NS092297, F31NS086168, R01NS083702, R01NS094224, R01NS094664)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- RET receptor tyrosine kinase, gate control theory of pain, dorsal horn, inhibitory interneurons, chronic pain, neuropathic pain, inflammatory pain, neuronal ablation, polysynaptic inhibition, nociceptive afferents
- MeSH terms
- Animals, Clozapine, Female, Interneurons, Male, Mice, Transgenic, Neural Inhibition, Neurons, Pain, Pain Measurement, Spinal Cord, Touch, Proto-Oncogene Proteins c-ret, Mice, Spinal Cord Dorsal Horn
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