ArticleMolecular cell2025
eEF2K regulates pain through translational control of BDNF.
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.
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Who cites it
7 citing papers in PubMed.
- Overactive Neuronal eEF2K/eEF2 signaling is associated with cognitive impairment and apathy-like behavior.Molecular psychiatry · 2026Article
- GCN2 regulates paclitaxel-induced neuropathic pain.British journal of pharmacology · 2025Article
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- The mRNA Translation Inhibitor Vioprolide A Prevents Inflammatory Pain-Like Behaviour With Limited Action on Already Established Pain-Like Behaviour in Mice.European journal of pain (London, England) · 2025Article
- Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.Frontiers in neurology · 2025Review
- The RNA-binding protein CELF4 is a negative regulator of sensory neuron excitability and mechanical and heat behavioral sensitivity.Neurobiology of pain (Cambridge, Mass.)Article
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Authors and funding
7 authors.
Funding
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.
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Registered trials
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.