Evidence map›Paper›PMID 20860833›Full record

ArticleMolecular pain2010

Endogenous N-acetylaspartylglutamate (NAAG) inhibits synaptic plasticity/transmission in the amygdala in a mouse inflammatory pain model.

Mary O Adedoyin, Stefano Vicini, Joseph H Neale

Open access · goldAbstract read
In one paragraph

Article in Molecular pain, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

57 citing papers in PubMed, 73 citations in OpenAlex.

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  17. Amygdala physiology in pain.Handbook of behavioral neuroscience · 2020
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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

3 authors at 1 institution in 1 country.

Mary O AdedoyinDepartment of Biology, Georgetown University, Biology Reiss Building 37th and O St. NW, Washington, D.C. 20057, USA.
Stefano Vicini
Joseph H Neale
Georgetown University · US

Funding

Training in Neural Injury &PlasticityT32NS041218 · NINDS · GEORGETOWN UNIVERSITY · PI MARK P BURNS, Kathleen Anne Maguire-Zeiss · 2001 to 2026
$3.5M
NAAG PEPTIDASE AND NEURONAL FUNCTIONR01NS038080 · NINDS · GEORGETOWN UNIVERSITY · PI NEALE, JOSEPH H · 2000 to 2008
$2.4M
NINDS NIH HHS R01 NS 38080NINDS NIH HHS T32 NS041218
6 · The paper itself

Abstract

backgroundThe peptide neurotransmitter N-acetylaspartylglutamate (NAAG) is widely expressed throughout the vertebrate nervous system, including the pain processing neuraxis. Inhibitors of NAAG peptidases are analgesic in animal models of pain. However, the brain regions involved in NAAG's analgesic action have not been rigorously defined. Group II metabotropic glutamate receptors (mGluR2/3) play a role in pain processing in the laterocapsular part of the central nucleus of the amygdala (CeLC). Given the high concentration of NAAG in the amygdala and its activation of group II mGluRs (mGluR3 > mGluR2), this study was undertaken using the mouse formalin model of inflammatory pain to test the hypothesis that NAAG influences pain processing in the amygdala. Evoked excitatory postsynaptic currents (eEPSCs) were studied in neurons in the CeLC of mouse brain slices following stimulation of the spinoparabrachial amygdaloid afferents.

resultsApplication of a NAAG peptidase inhibitor, ZJ43, dose dependently inhibited the amplitude of the eEPSCs by up to 50% in control CeLC demonstrating the role of NAAG in regulation of excitatory transmission at this synapse. A group II mGluR agonist (SLx-3095-1) similarly inhibited eEPSC amplitude by about 30%. Both effects were blocked by the group II mGluR antagonist LY341495. ZJ43 was much less effective than SLx in reducing eEPSCs 24 hours post inflammation suggesting an inflammation induced reduction in NAAG release or an increase in the ratio of mGluR2 to mGluR3 expression. Systemic injection of ZJ43 proximal to the time of inflammation blocked peripheral inflammation-induced increases in synaptic transmission of this pathway 24 hrs later and blocked the induction of mechanical allodynia that developed by this time point.

conclusionsThe main finding of this study is that NAAG and NAAG peptidase inhibition reduce excitatory neurotransmission and inflammation-induced plasticity at the spinoparabrachial synapse within the pain processing pathway of the central amygdaloid nucleus.

Indexed as

AmygdalaAnimalsBehavior, AnimalDipeptidesDisease Models, AnimalExcitatory Postsynaptic PotentialsFormaldehydeGlutamate Carboxypeptidase IIHyperalgesiaInflammationIn Vitro TechniquesMiceModels, BiologicalNeuronal PlasticityNociceptorsPainDipeptidesFormaldehydeGlutamate Carboxypeptidase IIisospaglumic acidReceptors, AMPAReceptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateUreaZJ43

Identifiers

PMID20860833
PMCPMC3152775
OpenAlexW2114462462

What OpenQuestion holds

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LicenceCC BY
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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.