Evidence mapPaperPMID 36430751Full record

ArticleInternational journal of molecular sciences2022

The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury.

Saskia Wedel, Lisa Hahnefeld, Mohamad Wessam Alnouri, Stefan Offermanns, Felix Hausch, Gerd Geisslinger, Marco Sisignano

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Dysregulation of sphingolipid metabolism in pain.Frontiers in pharmacology · 2024
    Review
  5. Article
  6. Review
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.

Saskia WedelInstitute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, University Hospital, Goethe-University, 60590 Frankfurt am Main, Germany.
Lisa HahnefeldInstitute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, University Hospital, Goethe-University, 60590 Frankfurt am Main, Germany.ORCID 0000-0002-0382-5695
Mohamad Wessam AlnouriMax Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Stefan OffermannsMax Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Felix HauschDepartment of Biochemistry, Technical University Darmstadt, 64287 Darmstadt, Germany.
Gerd GeisslingerInstitute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, University Hospital, Goethe-University, 60590 Frankfurt am Main, Germany.
Marco SisignanoInstitute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, University Hospital, Goethe-University, 60590 Frankfurt am Main, Germany.ORCID 0000-0002-7581-0951
Goethe University Frankfurt · DEMax Planck Institute for Heart and Lung Research · DETechnische Universität Darmstadt · DE

Funding

Deutsche Forschungsgemeinschaft 445757098Deutsche Forschungsgemeinschaft SFB 1039 A04Deutsche Forschungsgemeinschaft SFB1039 A09Deutsche Forschungsgemeinschaft SFB 1039 Z01Federal Ministry of Education and Research 51TaValP
6 · The paper itself

Abstract

Neuropathic pain is a pathological pain state with a broad symptom scope that affects patients after nerve injuries, but it can also arise after infections or exposure to toxic substances. Current treatment possibilities are still limited because of the low efficacy and severe adverse effects of available therapeutics, highlighting an emerging need for novel analgesics and for a detailed understanding of the pathophysiological alterations in the onset and maintenance of neuropathic pain. Here, we show that the novel and highly specific FKBP51 inhibitor SAFit2 restores lipid signaling and metabolism in nervous tissue after nerve injury. More specifically, we identify that SAFit2 restores the levels of the C16 dihydroceramide, which significantly reduces the sensitization of the pain-mediating TRPV1 channel and subsequently the secretion of the pro-inflammatory neuropeptide CGRP in primary sensory neurons. Furthermore, we show that the C16 dihydroceramide is capable of reducing acute thermal hypersensitivity in a capsaicin mouse model. In conclusion, we report for the first time the C16 dihydroceramide as a novel and crucial lipid mediator in the context of neuropathic pain as it has analgesic properties, contributing to the pain-relieving properties of SAFit2.

Indexed as

NeuralgiaTrauma, Nervous SystemAnalgesicsAnimalsCeramidesMiceAnalgesicsCeramidesdihydroceramideceramidesFKBP51lipid mediatorsnerve injuryneuropathic painsensory neurons

Identifiers

PMID36430751
PMCPMC9695264
OpenAlexW4309719930

What Socratic 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 Socratic graph.