Evidence map›Paper›PMID 25489099›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Inflammatory sensitization of nociceptors depends on activation of NMDA receptors in DRG satellite cells.

Luiz Fernando Ferrari, Celina Monteiro Lotufo, Dionéia Araldi, Marcos A Rodrigues, Larissa P Macedo, Sérgio H Ferreira, Carlos Amilcar Parada

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.8field-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

34 citing papers in PubMed, 67 citations in OpenAlex.

  1. Glial cells in neuropathic pain.Physiological reviews · 2026
    Review
  2. Article
  3. Review
  4. The Nociceptor Primary Cilium Contributes to Mechanical Nociceptive Threshold and Inflammatory and Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
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  12. Review
  13. Regulation of Mitochondrial Function by Epac2 Contributes to Acute Inflammatory Hyperalgesia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
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  16. Review
  17. 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

7 authors at 3 institutions in 1 country.

Luiz Fernando FerrariDepartment of Pharmacology, Faculty of Medicine, Ribeirão Preto University of São Paulo, Ribeirão Preto, 14049-900, São Paulo, Brazil;
Celina Monteiro LotufoDepartment of Pharmacology, Faculty of Medicine, Ribeirão Preto University of São Paulo, Ribeirão Preto, 14049-900, São Paulo, Brazil; Department of Physiological Science, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, 38400-902, Minas Gerais, Brazil; and.
Dionéia AraldiDepartment of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862, São Paulo, Brazil.
Marcos A RodriguesDepartment of Pharmacology, Faculty of Medicine, Ribeirão Preto University of São Paulo, Ribeirão Preto, 14049-900, São Paulo, Brazil;
Larissa P MacedoDepartment of Physiological Science, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, 38400-902, Minas Gerais, Brazil; and.
Sérgio H FerreiraDepartment of Pharmacology, Faculty of Medicine, Ribeirão Preto University of São Paulo, Ribeirão Preto, 14049-900, São Paulo, Brazil; shferrei@fmrp.usp.br caparada@unicamp.br.
Carlos Amilcar ParadaDepartment of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, 13083-862, São Paulo, Brazil shferrei@fmrp.usp.br caparada@unicamp.br.
Universidade de São Paulo · BRUniversidade Estadual de Campinas (UNICAMP) · BRUniversidade Federal de Uberlândia · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) in the L5-DRG. Moreover, blockade of DRG AMPA receptors by the antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect in the PGE2-induced hyperalgesia in the paw, showing specific involvement of NMDARs in this modulatory effect and suggesting that activation of NMDAR in the DRG plays an important role in the peripheral inflammatory hyperalgesia. In following experiments we observed attenuation of PGE2-induced hyperalgesia in the paw by the knockdown of NMDAR subunits NR1, NR2B, NR2D, and NR3A with antisense-oligodeoxynucleotide treatment in the DRG. Also, in vitro experiments showed that the NMDA-induced sensitization of cultured DRG neurons depends on satellite cell activation and on those same NMDAR subunits, suggesting their importance for the PGE2-induced hyperalgesia. In addition, fluorescent calcium imaging experiments in cultures of DRG cells showed induction of calcium transients by glutamate or NMDA only in satellite cells, but not in neurons. Together, the present results suggest that the mechanical inflammatory nociceptor sensitization is dependent on glutamate release at the DRG and subsequent NMDAR activation in satellite glial cells, supporting the idea that the peripheral hyperalgesia is an event modulated by a glutamatergic system in the DRG.

Indexed as

2-Amino-5-phosphonovalerateAnimalsDinoprostoneGanglia, SpinalHyperalgesiaNociceptorsQuinoxalinesRatsReceptors, AMPAReceptors, N-Methyl-D-AspartateSatellite Cells, Perineuronal2-Amino-5-phosphonovalerateDinoprostoneQuinoxalinesReceptors, AMPAReceptors, N-Methyl-D-Aspartatedorsal root ganglionhyperalgesiainflammatory painNMDA receptorsatellite cells

Identifiers

PMID25489099
PMCPMC4280647
OpenAlexW2061391090

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.