ArticleJournal of neurochemistry2019
Increased α2δ-1-NMDA receptor coupling potentiates glutamatergic input to spinal dorsal horn neurons in chemotherapy-induced neuropathic pain.
Article in Journal of neurochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Preclinical research in paclitaxel-induced neuropathic pain: a systematic review.Frontiers in veterinary science · 2023Pooled it
- Sensory neuron BRAF mediates opioid-induced hyperalgesia and tolerance via presynaptic NMDA receptor hyperactivity.The Journal of clinical investigation · 2026Article
- Emerging Pharmacological Strategies for Trigeminal Neuralgia.CNS drugs · 2026Review
- HIV-1 gp120 Induces Nociceptive Hypersensitivity via α2δ-1-Bound NMDA Receptors at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Efficacy of pregabalin in the treatment of acute cerebral hemorrhage and its influence on prognosis.Frontiers in pharmacology · 2026Article
- Tonic GABA and Glycine Inhibition Control Pain Hypersensitivity via Limiting α2δ-1- and mGluR5-Dependent NMDA Receptor Activity at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- LRRC8A constitutively inhibits pain hypersensitivity in rodent models by restraining NMDA receptor activity at spinal cord synapses.Science translational medicine · 2025Article
- GαScience signaling · 2025Article
- Pia Mater-Penetrable Lipopolymer Nanoparticles for Gliocyte-Targeted IL-10 mRNA Therapy Alleviate Paclitaxel-Induced Peripheral Neuropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- α2δ-2 regulates synaptic GluK1 kainate receptors in Purkinje cells and motor coordination.Brain : a journal of neurology · 2025Article
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- An electrophysiologist's guide to dorsal horn excitability and pain.Frontiers in cellular neuroscience · 2025Review
- Foxg1 Modulation of the Prkcd Gene in the Lateral Habenula Mediates Trigeminal Neuralgia-Associated Anxiety-Like Behaviors in Mice.Molecular neurobiology · 2024Article
- Calcineurin regulates synaptic CaThe Journal of physiology · 2024Article
- Constitutive KCC2 Cell- and Synapse-Specifically Regulates NMDA Receptor Activity in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The correlation between vitamin D and the occurrence of peripheral neuropathy induced by paclitaxel chemotherapy.Frontiers in medicine · 2024Article
- Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- Brain α2δ-1-Bound NMDA Receptors Drive Calcineurin Inhibitor-Induced Hypertension.Circulation research · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Painful peripheral neuropathy is a severe and difficult-to-treat neurological complication associated with cancer chemotherapy. Although chemotherapeutic drugs such as paclitaxel are known to cause tonic activation of presynaptic NMDA receptors (NMDARs) to potentiate nociceptive input, the molecular mechanism involved in this effect is unclear. α2δ-1, commonly known as a voltage-activated calcium channel subunit, is a newly discovered NMDAR-interacting protein and plays a critical role in NMDAR-mediated synaptic plasticity. Here we show that paclitaxel treatment in rats increases the α2δ-1 expression level in the dorsal root ganglion and spinal cord and the mRNA levels of GluN1, GluN2A, and GluN2B in the spinal cord. Paclitaxel treatment also potentiates the α2δ-1-NMDAR interaction and synaptic trafficking in the spinal cord. Strikingly, inhibiting α2δ-1 trafficking with pregabalin, disrupting the α2δ-1-NMDAR interaction with an α2δ-1 C-terminus-interfering peptide, or α2δ-1 genetic ablation fully reverses paclitaxel treatment-induced presynaptic NMDAR-mediated glutamate release from primary afferent terminals to spinal dorsal horn neurons. In addition, intrathecal injection of pregabalin or α2δ-1 C-terminus-interfering peptide and α2δ-1 knockout in mice markedly attenuate paclitaxel-induced pain hypersensitivity. Our findings indicate that α2δ-1 is required for paclitaxel-induced tonic activation of presynaptic NMDARs at the spinal cord level. Targeting α2δ-1-bound NMDARs, not the physiological α2δ-1-free NMDARs, may be a new strategy for treating chemotherapy-induced neuropathic pain. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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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.