ArticleNature medicine2015
Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers, 1 of them a synthesis that pooled it.
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Who cites it
206 citing papers in PubMed, 1 synthesis or guideline pooled it, 345 citations in OpenAlex.
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- Mechanisms of pruritus and advances in traditional Chinese medicine therapy (Review).Molecular medicine reports · 2026Review
- Circular RNA circNrip1 Interacts with SYNCRIP to Promote Neuropathic Pain by Stabilizing Tlr2 mRNA in Primary Sensory Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TWIK-1 plays distinct roles in spinal and peripheral sensory circuits controlling mechanical sensitivity and neuropathic hypersensitivity.Signal transduction and targeted therapy · 2026Article
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- Enhanced expression of spinal PTP1B contributes to peripheral inflammation- induced glycinergic disinhibition and mechanical pain.Communications biology · 2026Article
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- Neuroimmune interactions in cardiovascular homeostasis and disease.American journal of physiology. Cell physiology · 2026Review
- The miR-183/96/182 Cluster Regulates Trigeminal Ganglion Sensory Neurons' Response tobioRxiv : the preprint server for biology · 2026Article
- Contribution of proneurotrophin-3 to nerve trauma-induced neuropathic pain through promoting TrkC-mediated increase of CCL2 in primary sensory neurons.Brain, behavior, and immunity · 2026Article
- Targeting IL-6 as a novel therapeutic approach for alcohol abstinence - related mechanical allodynia.Neuropharmacology · 2025Article
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- In vivo Pirt-Marina voltage sensor imaging detects primary sensory neuron-specific voltage dynamics and neuronal plasticity changes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain.Cell · 2025Article
- Primary sensory neuron dysfunction underlying mechanical itch hypersensitivity in a Shank3 mouse model of autism.Translational psychiatry · 2025Article
146 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
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Abstract
Mechanical allodynia, induced by normally innocuous low-threshold mechanical stimulation, represents a cardinal feature of neuropathic pain. Blockade or ablation of high-threshold, small-diameter unmyelinated group C nerve fibers (C-fibers) has limited effects on mechanical allodynia. Although large, myelinated group A fibers, in particular Aβ-fibers, have previously been implicated in mechanical allodynia, an A-fiber-selective pharmacological blocker is still lacking. Here we report a new method for targeted silencing of A-fibers in neuropathic pain. We found that Toll-like receptor 5 (TLR5) is co-expressed with neurofilament-200 in large-diameter A-fiber neurons in the dorsal root ganglion (DRG). Activation of TLR5 with its ligand flagellin results in neuronal entry of the membrane-impermeable lidocaine derivative QX-314, leading to TLR5-dependent blockade of sodium currents, predominantly in A-fiber neurons of mouse DRGs. Intraplantar co-application of flagellin and QX-314 (flagellin/QX-314) dose-dependently suppresses mechanical allodynia after chemotherapy, nerve injury, and diabetic neuropathy, but this blockade is abrogated in Tlr5-deficient mice. In vivo electrophysiology demonstrated that co-application of flagellin/QX-314 selectively suppressed Aβ-fiber conduction in naive and chemotherapy-treated mice. TLR5-mediated Aβ-fiber blockade, but not capsaicin-mediated C-fiber blockade, also reduced chemotherapy-induced ongoing pain without impairing motor function. Finally, flagellin/QX-314 co-application suppressed sodium currents in large-diameter human DRG neurons. Thus, our findings provide a new tool for targeted silencing of Aβ-fibers and neuropathic pain treatment.
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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.