Evidence mapPaperPMID 39694034Full record

ArticleMolecular cell2025

eEF2K regulates pain through translational control of BDNF.

Patrick R Smith, Guadalupe Garcia, Angela R Meyer, Alexey G Ryazanov, Tao Ma, Sarah Loerch, Zachary T Campbell

Abstract read
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
field-weighted citation impact
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

7 citing papers in PubMed.

  1. Article
  2. GCN2 regulates paclitaxel-induced neuropathic pain.British journal of pharmacology · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
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.

Patrick R SmithDepartment of Anesthesiology, University of Wisconsin, Madison, Madison, WI, USA.
Guadalupe GarciaDepartment of Anesthesiology, University of Wisconsin, Madison, Madison, WI, USA.
Angela R MeyerDepartment of Anesthesiology, University of Wisconsin, Madison, Madison, WI, USA.
Alexey G RyazanovDepartment of Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Tao MaDepartment of Internal Medicine, Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Translational Neuroscience, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Sarah LoerchDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA, USA; Center for Molecular Biology of RNA, University of California, Santa Cruz, CA 95064, USA.
Zachary T CampbellDepartment of Anesthesiology, University of Wisconsin, Madison, Madison, WI, USA. Electronic address: zcampbell@wisc.edu.

Funding

Profiling Translation in Nociceptor PlasticityR01NS114018 · UNIVERSITY OF WISCONSIN-MADISON · 2025 to 2025
$622k
Molecular Mechanisms of Translation Regulation by the eEF2K PathwayR35GM146862 · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2025 to 2025
$377k
NIGMS NIH HHS R35 GM146862NINDS NIH HHS R01 NS114018
6 · The paper itself

Abstract

mRNA translation is integral to pain, yet the key regulatory factors and their target mRNAs are unclear. Here, we uncover a mechanism that bridges noxious insults to multiple phases of translational control in murine sensory neurons. We find that a painful cue triggers repression of peptide chain elongation through activation of elongation factor 2 kinase (eEF2K). Attenuated elongation is sensed by a ribosome-coupled mechanism that triggers the integrated stress response (ISR). Both eEF2K and the ISR are required for pain-associated behaviors in vivo. This pathway simultaneously induces biosynthesis of brain-derived neurotrophic factor (BDNF). Selective blockade of Bdnf translation has analgesic effects in vivo. Our data suggest that precise spatiotemporal regulation of Bdnf translation is critical for appropriate behavioral responses to painful stimuli. Overall, our results demonstrate that eEF2K resides at the nexus of an intricate regulatory network that links painful cues to multiple layers of translational control.

Indexed as

Brain-Derived Neurotrophic FactorElongation Factor 2 KinasePainProtein BiosynthesisSensory Receptor CellsAnimalsBehavior, AnimalGanglia, SpinalMaleMiceMice, Inbred C57BLPeptide Chain Elongation, TranslationalRibosomesRNA, MessengerBdnf protein, mouseBrain-Derived Neurotrophic FactorEef2k protein, mouseElongation Factor 2 KinaseRNA, MessengerBDNFeEF2KeIF2αGCN2integrated stress responsepainP-stalkselective translation

Identifiers

PMID39694034
PMCPMC11845307

What Socratic holds

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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.