ArticleBrain : a journal of neurology2024
Tomivosertib reduces ectopic activity in dorsal root ganglion neurons from patients with radiculopathy.
Article in Brain : a journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Lymphotoxin-beta receptor controls the development of chronic pain.Cell reports · 2026Article
- Transcriptome of the human C2 dorsal root ganglia in C1-2 arthrodesis surgery: insight for neck pain.Brain : a journal of neurology · 2026Article
- Human Dorsal Root Ganglia Neuronal Cell Line to Study Nociceptive Signaling: A New Pipeline for Pain Therapy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Decoding orofacial pain: a translational review of mechanisms and novel therapies.The journal of headache and pain · 2025Review
- Review
- Detection of probable neuronal gene expression changes in skin biopsies from patients with paclitaxel-induced peripheral neuropathy.bioRxiv : the preprint server for biology · 2025Article
- Type I IFNs enhance human dorsal root ganglion nociceptor excitability and induce TRPV1 sensitization.JCI insight · 2025Article
- Ectopic Nociceptor Sprouting as a Key Peripheral Driver of Pain in Rheumatoid Arthritis.Current rheumatology reports · 2025Review
- Mycobacterial Phenolic Glycolipid Triggers ATP-Mediated Neuronal P2X3 Signaling and Cough.bioRxiv : the preprint server for biology · 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
- Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models.bioRxiv : the preprint server for biology · 2024Article
- Interleukin-6 induces nascent protein synthesis in human dorsal root ganglion nociceptors primarily via MNK-eIF4E signaling.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined in preclinical models that drive spontaneous activity, none have been tested directly on spontaneously active human nociceptors. Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we showed that inhibition of mitogen-activated protein kinase interacting kinase (MNK) with tomivosertib (eFT508, 25 nM) reversibly suppresses spontaneous activity in human sensory neurons that are likely nociceptors based on size and action potential characteristics associated with painful dermatomes within minutes of treatment. Tomivosertib treatment also decreased action potential amplitude and produced alterations in the magnitude of after hyperpolarizing currents, suggesting modification of Na+ and K+ channel activity as a consequence of drug treatment. Parallel to the effects on electrophysiology, eFT508 treatment led to a profound loss of eIF4E serine 209 phosphorylation in primary sensory neurons, a specific substrate of MNK, within 2 min of drug treatment. Our results create a compelling case for the future testing of MNK inhibitors in clinical trials for neuropathic pain.
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Registered trials
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