Evidence map›Paper›PMID 32796542›Full record

ArticleCells2020

Schwann Cell Autocrine and Paracrine Regulatory Mechanisms, Mediated by Allopregnanolone and BDNF, Modulate PKCε in Peripheral Sensory Neurons.

Veronica Bonalume, Lucia Caffino, Luca F Castelnovo, Alessandro Faroni, Flavio Giavarini, Sheng Liu, Donatella Caruso, Martin Schmelz, Fabio Fumagalli, Richard W Carr and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  5. Axonal tuning by GABANeural regeneration research · 2023
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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 4 countries.

Veronica BonalumeDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0002-1185-2351
Lucia CaffinoDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
Luca F CastelnovoDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0003-4784-1221
Alessandro FaroniBlond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK.ORCID 0000-0003-4435-6423
Flavio GiavariniDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
Sheng LiuInstitute of Pharmacology, Heidelberg University, 68167 Mannheim, Germany.
Donatella CarusoDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0003-2115-778X
Martin SchmelzExperimental Pain Research, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.ORCID 0000-0002-9736-7241
Fabio FumagalliDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0002-8814-7706
Richard W CarrExperimental Pain Research, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Valerio MagnaghiDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.ORCID 0000-0002-6903-7042
University of Milan · ITHeidelberg University · DEUniversity of Manchester · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protein kinase type C-ε (PKCε) plays important roles in the sensitization of primary afferent nociceptors, such as ion channel phosphorylation, that in turn promotes mechanical hyperalgesia and pain chronification. In these neurons, PKCε is modulated through the local release of mediators by the surrounding Schwann cells (SCs). The progesterone metabolite allopregnanolone (ALLO) is endogenously synthesized by SCs, whereas it has proven to be a crucial mediator of neuron-glia interaction in peripheral nerve fibers. Biomolecular and pharmacological studies on rat primary SCs and dorsal root ganglia (DRG) neuronal cultures were aimed at investigating the hypothesis that ALLO modulates neuronal PKCε, playing a role in peripheral nociception. We found that SCs tonically release ALLO, which, in turn, autocrinally upregulated the synthesis of the growth factor brain-derived neurotrophic factor (BDNF). Subsequently, glial BDNF paracrinally activates PKCε via trkB in DRG sensory neurons. Herein, we report a novel mechanism of SCs-neuron cross-talk in the peripheral nervous system, highlighting a key role of ALLO and BDNF in nociceptor sensitization. These findings emphasize promising targets for inhibiting the development and chronification of neuropathic pain.

Indexed as

AnimalsAutocrine CommunicationBlotting, WesternBrain-Derived Neurotrophic FactorCells, CulturedChromatography, LiquidEnzyme-Linked Immunosorbent AssayFluorescent Antibody TechniqueGanglia, SpinalHumansHyperalgesiaNeuralgiaParacrine CommunicationPregnanoloneRats, Sprague-DawleySchwann Cellsbrain-derived growth factorBrain-Derived Neurotrophic FactorPregnanolonedorsal root gangliahyperalgesianeuroactive steroidneuro-glia interactionneuropathic pain

Identifiers

PMID32796542
PMCPMC7465687
OpenAlexW3048449951

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.