ReviewCellular and molecular life sciences : CMLS2019
Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain.
Review in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Quantitative analysis of nortriptyline's analgesic properties: a comparative systematic review and meta-analysis.BMJ open · 2024Pooled it
- Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials.Frontiers in neurology · 2022Pooled it
- Sublingual Administration for Pain Control: Pharmacology, Clinical Applications and Future Directions.CNS drugs · 2026Review
- Dapsone and N-Acetylcysteine Exert a Synergistic Antinociceptive Effect Associated with Oxidative Stress After Traumatic Spinal Cord Injury: An Isobolographic Study.Brain sciences · 2026Article
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
- Ketamine Dosing Across Clinical Indications: A Narrative Review Organized by Proposed NMDA-Related Mechanisms.Journal of clinical pharmacology · 2026Review
- Melatonin Mitigates Central Sensitization and Nociplastic Pain in Spinal Cord and Dorsal Root Ganglia of FM Rat Model: Modulation of SIRT1/PGC-1α/MAPK/NF-κB Signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- EGFR activation sensitizes trigeminal NMDA receptors to promote pain and morphine analgesic tolerance in oral cancer.Science signaling · 2026Article
- The excitatory neurotransmitter glutamate and its receptors: the culprits behind neuropathic pain?Frontiers in aging neuroscience · 2026Review
- 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
- Article
- GαScience signaling · 2025Article
- New Diagnostic and Therapeutic Targets for Spinal Cord Injury: GRN Gene.Journal of cellular and molecular medicine · 2025Article
- Involvement of TRPV1 and MOR-NMDAR complex on the antiallodynic effect of LMH-2, a sigma-1 receptor antagonist, in mouse model of diabetic neuropathy - a behavioral approach.Pharmacological reports : PR · 2025Article
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- New Synthesis and Pharmacological Evaluation of Enantiomerically Pure (Journal of medicinal chemistry · 2025Article
- Platinum Deposition in the Central Nervous System: A Novel Insight into Oxaliplatin-induced Peripheral Neuropathy in Young and Old Mice.Molecular neurobiology · 2025Article
- Upregulation of NR2B Subunits of NMDA Receptors in the Lateral Parabrachial Nucleus Contributes to Chronic Pancreatitis Pain.CNS neuroscience & therapeutics · 2025Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Chronic neuropathic pain is a debilitating condition that remains challenging to treat. Glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been used to treat neuropathic pain, but the exact sites of their actions have been unclear until recently. Although conventionally postsynaptic, NMDARs are also expressed presynaptically, particularly at the central terminals of primary sensory neurons, in the spinal dorsal horn. However, presynaptic NMDARs in the spinal cord are normally quiescent and are not actively involved in physiological nociceptive transmission. In this review, we describe the emerging role of presynaptic NMDARs at the spinal cord level in chronic neuropathic pain and the implications of molecular mechanisms for more effective treatment. Recent studies indicate that presynaptic NMDAR activity at the spinal cord level is increased in several neuropathic pain conditions but not in chronic inflammatory pain. Increased presynaptic NMDAR activity can potentiate glutamate release from primary afferent terminals to spinal dorsal horn neurons, which is crucial for the synaptic plasticity associated with neuropathic pain caused by traumatic nerve injury and chemotherapy-induced peripheral neuropathy. Furthermore, α2δ-1, previously considered a calcium channel subunit, can directly interact with NMDARs through its C-terminus to increase presynaptic NMDAR activity by facilitating synaptic trafficking of α2δ-1-NMDAR complexes in neuropathic pain caused by chemotherapeutic agents and peripheral nerve injury. Targeting α2δ-1-bound NMDARs with gabapentinoids or α2δ-1 C-terminus peptides can attenuate nociceptive drive form primary sensory nerves to dorsal horn neurons in neuropathic pain.
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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.