Evidence map›Paper›PMID 22553041›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012

5,6-EET is released upon neuronal activity and induces mechanical pain hypersensitivity via TRPA1 on central afferent terminals.

Marco Sisignano, Chul-Kyu Park, Carlo Angioni, Dong Dong Zhang, Christian von Hehn, Enrique J Cobos, Nader Ghasemlou, Zhen-Zhong Xu, Vigneswara Kumaran, Ruirui Lu and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
7.9field-weighted citation impact, top 1% 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

66 citing papers in PubMed, 133 citations in OpenAlex.

  1. The Roles of EETs in Neurological Disorders.CNS neuroscience & therapeutics · 2026
    Review
  2. Review
  3. Article
  4. Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Endogenous Derivatives of Linoleic Acid and their Stable Analogs Are Potential Pain Mediators.JID innovations : skin science from molecules to population health · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Antioxidants (Basel, Switzerland) · 2022
    Article
  14. Review
  15. Review
  16. Review
  17. Lysophospholipids Contribute to Oxaliplatin-Induced Acute Peripheral Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  18. Review
  19. Review
  20. Article

6 more citing papers are in PubMed but not listed here.

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

19 authors at 6 institutions in 3 countries.

Marco SisignanoInstitute of Clinical Pharmacology, Pharmazentrum Frankfurt/Center for Drug Research, Development and Safety (ZAFES), University Hospital, Goethe-University, D-60590 Frankfurt am Main, Germany.
Chul-Kyu Park
Carlo Angioni
Dong Dong Zhang
Christian von Hehn
Enrique J Cobos
Nader Ghasemlou
Zhen-Zhong Xu
Vigneswara Kumaran
Ruirui Lu
Andrew Grant
Michael J M Fischer
Achim Schmidtko
Peter Reeh
Ru-Rong Ji
Clifford J Woolf
Gerd Geisslinger
Klaus Scholich
Christian Brenneis
Goethe University Frankfurt · DEHarvard University · USBrigham and Women's Hospital · USKing's College London · GBFriedrich-Alexander-Universität Erlangen-Nürnberg · DEUniversity of Cambridge · GB

Funding

ALTERED SENSIBILITY FOLLOWING PERIPHERAL NERVE DAMAGER01NS038253 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI WOOLF, CLIFFORD J · 1999 to 2017
$8.2M
TRP Channel Mediated Pain CircuitryP01NS072040 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI WOOLF, CLIFFORD J · 2011 to 2015
$6.7M
Neural Plasticity and Inflammatory PainR37NS039518 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI WOOLF, CLIFFORD J · 2011 to 2017
$4.7M
Neural Plasticity and Inflammatory PainR01NS039518 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI WOOLF, CLIFFORD J · 2001 to 2010
$4.1M
Biotechnology and Biological Sciences Research Council BB/E527098/1NINDS NIH HHS 1P01NS072040NINDS NIH HHS 2R37 NS039518-08NINDS NIH HHS P01 NS072040NINDS NIH HHS R01 NS038253NINDS NIH HHS R01 NS039518NINDS NIH HHS R37 NS039518
6 · The paper itself

Abstract

Epoxyeicosatrienoic acids (EETs) are cytochrome P450-epoxygenase-derived metabolites of arachidonic acid that act as endogenous signaling molecules in multiple biological systems. Here we have investigated the specific contribution of 5,6-EET to transient receptor potential (TRP) channel activation in nociceptor neurons and its consequence for nociceptive processing. We found that, during capsaicin-induced nociception, 5,6-EET levels increased in dorsal root ganglia (DRGs) and the dorsal spinal cord, and 5,6-EET is released from activated sensory neurons in vitro. 5,6-EET potently induced a calcium flux (100 nm) in cultured DRG neurons that was completely abolished when TRPA1 was deleted or inhibited. In spinal cord slices, 5,6-EET dose dependently enhanced the frequency, but not the amplitude, of spontaneous EPSCs (sEPSCs) in lamina II neurons that also responded to mustard oil (allyl isothiocyanate), indicating a presynaptic action. Furthermore, 5,6-EET-induced enhancement of sEPSC frequency was abolished in TRPA1-null mice, suggesting that 5,6-EET presynaptically facilitated spinal cord synaptic transmission by TRPA1. Finally, in vivo intrathecal injection of 5,6-EET caused mechanical allodynia in wild-type but not TRPA1-null mice. We conclude that 5,6-EET is synthesized on the acute activation of nociceptors and can produce mechanical hypersensitivity via TRPA1 at central afferent terminals in the spinal cord.

Indexed as

8,11,14-Eicosatrienoic AcidAction PotentialsAfferent PathwaysAnimalsCells, CulturedHyperalgesiaMaleMiceMice, Inbred C57BLMice, KnockoutSensory Receptor Cells5,6-epoxy-8,11,14-eicosatrienoic acid8,11,14-Eicosatrienoic Acid

Identifiers

PMID22553041
PMCPMC3359875
OpenAlexW2164837602

What OpenQuestion holds

Textmetadata
LicenceTDM
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.