ArticleeLife2023
Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Diosgenin activates ERα-dependent PI3K/AKT/GSK3β signaling to enhance brain-derived serotonin and alleviate postmenopausal bone loss.Journal of advanced research · 2026Article
- Descending inhibitory rostral ventromedial medulla neurons cause widespread antinociception and contribute to the pain-inhibits-pain phenomenon.Nature communications · 2026Article
- Lumbar spinal Shox2 interneurons receive monosynaptic excitatory input from the lateral paragigantocellular nucleus in mouse.iScience · 2026Article
- Compensatory scaling of modulatory neural populations in response to motor challenges.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- An intra-brainstem circuitry for pain-induced inhibition of itch.Neuroscience · 2025Article
- Select terpenes from Cannabis sativa are antinociceptive in mouse models of post-operative pain and fibromyalgia via adenosine APharmacological reports : PR · 2025Article
- Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson's disease.NPJ Parkinson's disease · 2025Article
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- Lateral lamina V projection neuron axon collaterals connect sensory processing across the dorsal horn of the mouse spinal cord.Scientific reports · 2024Article
- Morphine-responsive neurons that regulate mechanical antinociception.Science (New York, N.Y.) · 2024Article
- Modulating Neural Circuits of Pain in Preclinical Models: Recent Insights for Future Therapeutics.Cells · 2024Review
- The 'in's and out's' of descending pain modulation from the rostral ventromedial medulla.Trends in neurosciences · 2024Review
- Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation.Science advances · 2024Article
- Central mechanisms of muscle tone regulation: implications for pain and performance.Frontiers in neuroscience · 2024Article
- Neuroanatomy of the nociceptive system: From nociceptors to brain networks.International review of neurobiology · 2024Review
- Understanding of Spinal Wide Dynamic Range Neurons and Their Modulation on Pathological Pain.Journal of pain research · 2024Review
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Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinally projecting serotonergic neurons play a key role in controlling pain sensitivity and can either increase or decrease nociception depending on physiological context. It is currently unknown how serotonergic neurons mediate these opposing effects. Utilizing virus-based strategies and Tph2-Cre transgenic mice, we identified two anatomically separated populations of serotonergic hindbrain neurons located in the lateral paragigantocellularis (LPGi) and the medial hindbrain, which respectively innervate the superficial and deep spinal dorsal horn and have contrasting effects on sensory perception. Our tracing experiments revealed that serotonergic neurons of the LPGi were much more susceptible to transduction with spinally injected AAV2retro vectors than medial hindbrain serotonergic neurons. Taking advantage of this difference, we employed intersectional chemogenetic approaches to demonstrate that activation of the LPGi serotonergic projections decreases thermal sensitivity, whereas activation of medial serotonergic neurons increases sensitivity to mechanical von Frey stimulation. Together these results suggest that there are functionally distinct classes of serotonergic hindbrain neurons that differ in their anatomical location in the hindbrain, their postsynaptic targets in the spinal cord, and their impact on nociceptive sensitivity. The LPGi neurons that give rise to rather global and bilateral projections throughout the rostrocaudal extent of the spinal cord appear to be ideally poised to contribute to widespread systemic pain control.
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