ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Reversal of peripheral nerve injury-induced neuropathic pain and cognitive dysfunction via genetic and tomivosertib targeting of MNK.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Evidence for Cognitive Decline in Chronic Pain: A Systematic Review and Meta-Analysis.Frontiers in neuroscience · 2021Pooled it
- Distinct roles for MNK1 and MNK2 in social and cognitive behavior through kinase-specific regulation of the synaptic proteome and phosphoproteome.Molecular psychiatry · 2026Article
- Live cell imaging reveals paclitaxel-induced lysosome motility and function disruption in DRG neurons.bioRxiv : the preprint server for biology · 2026Article
- Type I IFNs enhance human dorsal root ganglion nociceptor excitability and induce TRPV1 sensitization.JCI insight · 2025Article
- Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy.Nature communications · 2025Article
- Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.Frontiers in neurology · 2025Review
- Activation of 5-HTMolecular neurobiology · 2025Article
- Tomivosertib reduces ectopic activity in dorsal root ganglion neurons from patients with radiculopathy.Brain : a journal of neurology · 2024Article
- ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.Pharmacological research · 2024Article
- Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction.iScience · 2024Article
- MiR-125b targeted regulation of MKNK2 inhibits multiple myeloma proliferation and invasion.American journal of translational research · 2024Article
- SARS-CoV-2 airway infection results in the development of somatosensory abnormalities in a hamster model.Science signaling · 2023Article
- The Emerging Translational Potential of MNK Inhibitors for the Treatment of Chronic Pain.Neuroscience · 2023Article
- MNK1 and MNK2 expression in the human dorsal root and trigeminal ganglion.bioRxiv : the preprint server for biology · 2023Article
- From Translation to Treatment.Faculty reviews · 2023Review
- Nociceptors: Their Role in Body's Defenses, Tissue Specific Variations and Anatomical Update.Journal of pain research · 2022Review
- Challenges and opportunities in translational pain research - An opinion paper of the working group on translational pain research of the European pain federation (EFIC).European journal of pain (London, England) · 2021Article
- Factors mediating pain-related risk for opioid use disorder.Neuropharmacology · 2021Review
- A Highly Selective MNK Inhibitor Rescues Deficits Associated with Fragile X Syndrome in Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Pharmacological Manipulation of Translation as a Therapeutic Target for Chronic Pain.Pharmacological reviews · 2021Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Neuropathic pain caused by nerve injury presents with severe spontaneous pain and a variety of comorbidities, including deficits in higher executive functions. None of these clinical problems are adequately treated with current analgesics. Targeting of the mitogen-activated protein kinase-interacting kinase (MNK1/2) and its phosphorylation target, the mRNA cap binding protein eIF4E, attenuates many types of nociceptive plasticity induced by inflammatory mediators and chemotherapeutic drugs but inhibiting this pathway does not alter nerve injury-induced mechanical allodynia. We used genetic manipulations and pharmacology to inhibit MNK-eIF4E activity in animals with spared nerve injury, a model of peripheral nerve injury (PNI)-induced neuropathic pain. We assessed the presence of spontaneous pain using conditioned place preference. We also tested performance in a medial prefrontal cortex (mPFC)-dependent rule-shifting task. WT neuropathic animals showed signs of spontaneous pain and were significantly impaired in the rule-shifting task while genetic and pharmacological inhibition of the MNK-eIF4E signaling axis protected against and reversed spontaneous pain and PNI-mediated cognitive impairment. Additionally, pharmacological and genetic inhibition of MNK-eIF4E signaling completely blocked and reversed maladaptive shortening in the length of axon initial segments (AIS) in the mPFC of PNI mice. Surprisingly, these striking positive outcomes on neuropathic pain occurred in the absence of any effect on mechanical allodynia, a standard test for neuropathic pain efficacy. Our results illustrate new testing paradigms for determining preclinical neuropathic pain efficacy and point to the MNK inhibitor tomivosertib (eFT508) as an important drug candidate for neuropathic pain treatment.
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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 OpenQuestion graph.