Evidence map›Paper›PMID 30203849›Full record

ArticleJournal of neurochemistry2018

Regulating nociceptive transmission by VGluT2-expressing spinal dorsal horn neurons.

Li Wang, Shao-Rui Chen, Huijie Ma, Hong Chen, Walter N Hittelman, Hui-Lin Pan

Open access · bronzeAbstract read
In one paragraph

Article in Journal of neurochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. HIV-1 gp120 Induces Nociceptive Hypersensitivity via α2δ-1-Bound NMDA Receptors at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Pharmacological and Genetic Approaches to Downregulate FIS1 Mitigate Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  7. Article
  8. Article
  9. Calcineurin and CK2 Reciprocally Regulate Synaptic AMPA Receptor Phenotypes via α2δ-1 in Spinal Excitatory Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  10. Constitutive KCC2 Cell- and Synapse-Specifically Regulates NMDA Receptor Activity in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  11. Review
  12. Optogenetic and Chemogenic Control of Pain Signaling: Molecular Markers.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Li WangCenter for Neuroscience and Pain Research, Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shao-Rui ChenCenter for Neuroscience and Pain Research, Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Huijie MaCenter for Neuroscience and Pain Research, Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Hong ChenCenter for Neuroscience and Pain Research, Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Walter N HittelmanDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Hui-Lin PanCenter for Neuroscience and Pain Research, Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0001-8444-3770
The University of Texas MD Anderson Cancer Center · USHebei Medical University · CN

Funding

Molecular Determinants of Synaptic Plasticity in Chronic PainR01NS101880 · NINDS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Shao-Rui Chen, Hui-Lin Pan · 2017 to 2026
$4.1M
Mechanisms of Neuronal Plasticity in Neuropathic PainR01GM120844 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI PAN, HUI-LIN · 2016 to 2019
$1.6M
NIGMS NIH HHS R01 GM120844NIH HHS GM120844NINDS NIH HHS R01 NS101880
6 · The paper itself

Abstract

Vesicular glutamate transporter-2 (VGluT2) mediates the uptake of glutamate into synaptic vesicles in neurons. Spinal cord dorsal horn interneurons are highly heterogeneous and molecularly diverse. The functional significance of VGluT2-expressing dorsal horn neurons in physiological and pathological pain conditions has not been explicitly demonstrated. Designer receptors exclusively activated by designer drugs (DREADDs) are a powerful chemogenetic tool to reversibly control neuronal excitability and behavior. Here, we used transgenic mice with Cre recombinase expression driven by the VGluT2 promoter, combined with the chemogenetic approach, to determine the contribution of VGluT2-expressing dorsal horn neurons to nociceptive regulation. Adeno-associated viral vectors expressing double-floxed Cre-dependent Gαq-coupled human M3 muscarinic receptor DREADD (hM3D)-mCherry or Gαi-coupled κ-opioid receptor DREADD (KORD)-IRES-mCitrine were microinjected into the superficial spinal dorsal horn of VGluT2-Cre mice. Immunofluorescence labeling showed that VGluT2 was predominantly expressed in lamina II excitatory interneurons. Activation of excitatory hM3D in VGluT2-expressing neurons with clozapine N-oxide caused a profound increase in neuronal firing and synaptic glutamate release. Conversely, activation of inhibitory KORD in VGluT2-expressing neurons with salvinorin B markedly inhibited neuronal activity and synaptic glutamate release. In addition, chemogenetic stimulation of VGluT2-expressing neurons increased mechanical and thermal sensitivities in naive mice, whereas chemogenetic silencing of VGluT2-expressing neurons reversed pain hypersensitivity induced by tissue inflammation and peripheral nerve injury. These findings indicate that VGluT2-expressing excitatory neurons play a crucial role in mediating nociceptive transmission in the spinal dorsal horn. Targeting glutamatergic dorsal horn neurons with inhibitory DREADDs may be a new strategy for treating inflammatory pain and neuropathic pain.

Indexed as

NociceptionSynaptic TransmissionAnimalsElectrophysiological PhenomenaHumansHyperalgesiaMiceMice, Inbred C57BLMice, TransgenicNeuralgiaPainPain ThresholdPeripheral Nerve InjuriesPosterior Horn CellsReceptor, Muscarinic M2Vesicular Glutamate Transport Protein 2CHRM2 protein, humanReceptor, Muscarinic M2SLC17A6 protein, humanVesicular Glutamate Transport Protein 2chemogeneticselectrophysiologyinflammatory paininterneuronsneuronal circutrysynaptic plasticity

Identifiers

PMID30203849
PMCPMC6263733
OpenAlexW2891389396

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.