Evidence map›Paper›PMID 27798132›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016

Gi-DREADD Expression in Peripheral Nerves Produces Ligand-Dependent Analgesia, as well as Ligand-Independent Functional Changes in Sensory Neurons.

Jami L Saloman, Nicole N Scheff, Lindsey M Snyder, Sarah E Ross, Brian M Davis, Michael S Gold

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

60 citing papers in PubMed, 94 citations in OpenAlex.

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  11. Gene therapy for chronic pain management.Cell reports. Medicine · 2024
    Review
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  19. The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  20. AAV-mediated gene transfer to colon-innervating primary afferent neurons.Frontiers in pain research (Lausanne, Switzerland) · 2023
    Article
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.

Jami L SalomanDepartments of Neurobiology and.ORCID 0000-0001-6093-6511
Nicole N ScheffAnesthesiology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261.
Lindsey M SnyderDepartments of Neurobiology and.
Sarah E RossDepartments of Neurobiology and.
Brian M DavisDepartments of Neurobiology and bmd1@pitt.edu.
Michael S GoldDepartments of Neurobiology and.
Institute of Neurobiology · BGUniversity of Pittsburgh · US

Funding

Investigating the Neural Circuits of ItchR01AR063772 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI H Richard Koerber, Sarah Elizabeth Ross · 2013 to 2026
$6.9M
Training in the Neurobiology of Neurological DiseaseT32NS086749 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Omar El Gharbawie, REBECCA P SEAL · 2014 to 2026
$4.8M
Training in Mechanisms and Clinical Presentation of PainT32NS073548 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jami Lynn Saloman, BRADLEY K. TAYLOR · 2012 to 2026
$3.1M
Role of Neurogenic Inflammation in Pancreatic CancerR01CA177857 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVIS, BRIAN M · 2013 to 2017
$2.1M
Mechanisms of MigraineR01NS083347 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GOLD, MICHAEL S · 2014 to 2018
$1.8M
Using dual intersectional genetics to understand and modulate itchR21AR064445 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROSS, SARAH ELIZABETH · 2013 to 2014
$358k
Understanding a specific microcircuit that integrates somatosensory information in the dorsal spinal cordF31NS092146 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SNYDER, LINDSEY M · 2015 to 2016
$83k
Injury-induced Dysregulation of Intracellular Ca2+ in Nociceptive AfferentsF31NS084661 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCHEFF, NICOLE N · 2013 to 2013
$42k
NCI NIH HHS R01 CA177857NIAMS NIH HHS R01 AR063772NIAMS NIH HHS R21 AR064445NINDS NIH HHS F31 NS084661NINDS NIH HHS F31 NS092146NINDS NIH HHS R01 NS083347NINDS NIH HHS T32 NS073548NINDS NIH HHS T32 NS086749
6 · The paper itself

Abstract

Designer receptors exclusively activated by designer drugs (DREADDs) are an advanced experimental tool that could potentially provide a novel approach to pain management. In particular, expression of an inhibitory (Gi-coupled) DREADD in nociceptors might enable ligand-dependent analgesia. To test this possibility, TRPV1-cre mice were used to restrict expression of Gi-DREADDs to predominantly C-fibers. Whereas baseline heat thresholds in both male and female mice expressing Gi-DREADD were normal, 1 mg/kg clozapine-N-oxide (CNO) produced a significant 3 h increase in heat threshold that returned to baseline by 5 h after injection. Consistent with these behavioral results, CNO decreased action potential firing in isolated sensory neurons from Gi-DREADD mice. Unexpectedly, however, the expression of Gi-DREADD in sensory neurons caused significant changes in voltage-gated Ca SIGNIFICANCE STATEMENT: DREADD technology is a powerful tool enabling manipulation of activity and/or transmitter release from targeted cell populations. The purpose of this study was to determine whether inhibitory DREADDs in nociceptive afferents could be used to produce analgesia, and if so, how. DREADD activation produced a ligand-dependent analgesia to heat in vivo and a decrease in neuronal firing at the single-cell level. However, we observed that expression of Gi-DREADD also causes ligand-independent changes in ion channel activity and second-messenger signaling. These findings highlight both the potential and the limitations of this exciting technology as well as the necessity to identify the mechanisms underlying any observed phenotype.

Indexed as

AnalgesiaAnimalsBehavior, AnimalCalcium ChannelsClozapineDesigner DrugsFemaleMaleMiceNociceptorsPain MeasurementPain ThresholdPatch-Clamp TechniquesPeripheral NervesPotassium Channels, Voltage-GatedReceptors, G-Protein-CoupledCalcium ChannelsClozapineDesigner DrugsPotassium Channels, Voltage-GatedReceptors, G-Protein-CoupledTRPV1 protein, mouseTRPV Cation ChannelsanalgesiaDREADDGPCRnociceptionpainsecond messenger

Identifiers

PMID27798132
PMCPMC5083007
OpenAlexW2536415787

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.