Evidence map›Paper›PMID 26164299›Full record

ArticleAnesthesiology2015

Silencing the α2 subunit of γ-aminobutyric acid type A receptors in rat dorsal root ganglia reveals its major role in antinociception posttraumatic nerve injury.

Aleksandar L Obradovic, Joseph Scarpa, Hari P Osuru, Janelle L Weaver, Ji-Yong Park, Sriyani Pathirathna, Alexander Peterkin, Yunhee Lim, Miljenko M Jagodic, Slobodan M Todorovic and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Anesthesiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Glial cells in neuropathic pain.Physiological reviews · 2026
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  11. Chloride - The Underrated Ion in Nociceptors.Frontiers in neuroscience · 2020
    Review
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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

11 authors at 3 institutions in 2 countries.

Aleksandar L ObradovicFrom the Departments of Anesthesiology (A.L.O., J.S., H.P.O., J.L.W., J.-Y.P., S.P., A.P., Y.L., M.M.J., S.M.T., V.J.-T.) and Neuroscience (S.M.T., V.J.-T.), University of Virginia Health System, Charlottesville, Virginia; Department of Physiology, University of Belgrade School of Pharmacy, Belgrade, Serbia (A.L.O.); Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York (J.S.); Department of Anesthesiology and Pain Medicine, College of Medicine, Korea University, Seoul, Republic of Korea (J.-Y.P.); and Department of Anesthesiology and Pain Medicine, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Republic of Korea (Y.L.).
Joseph Scarpa
Hari P Osuru
Janelle L Weaver
Ji-Yong Park
Sriyani Pathirathna
Alexander Peterkin
Yunhee Lim
Miljenko M Jagodic
Slobodan M Todorovic
Vesna Jevtovic-Todorovic
University of Belgrade · RSUniversity of Virginia Health System · USZero to Three · US

Funding

TRAINING IN CELL AND MOLECULAR BIOLOGYT32GM008136 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI STUKENBERG, P. TODD · 1985 to 2020
$8.5M
Validation of voltage-dependent T-channel blockers in treatment of neuropathic paR21DA029342 · NIDA · UNIVERSITY OF VIRGINIA · PI JEVTOVIC-TODOROVIC, VESNA, TODOROVIC, SLOBODAN M. · 2010 to 2011
$383k
NIDA NIH HHS R21 DA029342NIDA NIH HHS R21-DA029342NIGMS NIH HHS T32 GM008136
6 · The paper itself

Abstract

backgroundNeuropathic pain (NPP) is likely the result of repetitive high-frequency bursts of peripheral afferent activity leading to long-lasting changes in synaptic plasticity in the spinal dorsal horn. Drugs that promote γ-aminobutyric acid (GABA) activity in the dorsal horn provide partial relief of neuropathic symptoms. The authors examined how in vivo silencing of the GABA receptor type A (GABAA) α2 gene in dorsal root ganglia (DRG) controls NPP.

methodsAfter crush injury to the right sciatic nerve of female rats, the α2 GABAA antisense and mismatch oligodeoxynucleotides or NO-711 (a GABA uptake inhibitor) were applied to the L5 DRG. In vivo behavioral assessment of nociception was conducted before the injury and ensuing 10 days (n = 4 to 10). In vitro quantification of α2 GABAA protein and electrophysiological studies of GABAA currents were performed on acutely dissociated L5 DRG neurons at relevant time points (n = 6 to 14).

resultsNPP postcrush injury of a sciatic nerve in adult female rats coincides with significant down-regulation of the α2 subunit expression in the ipsilateral DRG (approximately 30%). Selective down-regulation of α2 expression in DRGs significantly worsens mechanical (2.55 ± 0.75 to 5.16 ± 1.16) and thermal (7.97 ± 0.96 to 5.51 ± 0.75) hypersensitivity in crush-injured animals and causes development of significant mechanical (2.33 ± 0.40 to 5.00 ± 0.33) and thermal (10.80 ± 0.29 to 7.34 ± 0.81) hypersensitivity in sham animals (data shown as mean ± SD). Conversely, up-regulation of endogenous GABA via blockade of its uptake in DRG alleviates NPP.

conclusionThe GABAA receptor in the DRG plays an important role in pathophysiology of NPP caused by sciatic nerve injury and represents promising target for novel pain therapies.

Indexed as

AnimalsFemaleGABA AntagonistsGanglia, SpinalNeuralgiaNipecotic AcidsOximesPain MeasurementPeripheral Nerve InjuriesRatsRats, Sprague-DawleyReceptors, GABA-ASciatic NeuropathyGABA AntagonistsGabra2 protein, ratNipecotic AcidsNNC 711OximesReceptors, GABA-A

Identifiers

PMID26164299
PMCPMC4568754
OpenAlexW1574019868

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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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.