ArticleNature neuroscience2011
Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit.
Article in Nature neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Time-dependent efficacy of zinc supplements in preventing oral mucositis after chemoradiotherapy: a meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Pooled it
- Potential Role of Zn Supplementation in Ameliorating Reserpine-Induced Fibromyalgia Manifestations Through Central NLRP3-Autophagy-Redox Network Modulation in Rats.Neurochemical research · 2026Article
- An emerging role for synaptic ZnPharmacology & therapeutics · 2026Review
- Dietetic Prescriptions in Bipolar Disorder: Nutritional Strategies to Support Mood Stability and Reduce Relapse Risk-A Narrative Review.Life (Basel, Switzerland) · 2026Review
- Dynamic control of NMDA receptor CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Examination of the relationship between serum zinc levels and peripheral neuropathy induced by paclitaxel/carboplatin combination therapy in gynecological cancer patients.Fujita medical journal · 2025Article
- Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice.PLoS biology · 2024Article
- Zinc Administration Favorably Affects Prophylactic Therapy-refractory Migraine Attacks: A Case Series.Internal medicine (Tokyo, Japan) · 2024Article
- Expression analysis of zinc-metabolizing enzymes in the saliva as a new method of evaluating zinc content in the body: two case reports and a review of the literature.Journal of medical case reports · 2024Review
- Single-fiber probes for combined sensing and imaging in biological tissue: recent developments and prospects.Biomedical optics express · 2024Review
- GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.Science advances · 2024Article
- Synaptic zinc potentiates AMPA receptor function in mouse auditory cortex.Cell reports · 2023Article
- The Therapeutic Potential of Antioxidants in Chemotherapy-Induced Peripheral Neuropathy: Evidence from Preclinical and Clinical Studies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology.Frontiers in molecular neuroscience · 2023Review
- ZniScience · 2022Article
- The Influence of Dietary Supplementations on Neuropathic Pain.Life (Basel, Switzerland) · 2022Review
- Recent advances in pain management based on nanoparticle technologies.Journal of nanobiotechnology · 2022Review
- Dissociation of nanosilicates induces downstream endochondral differentiation gene expression program.Science advances · 2022Article
- Activity-dependent modulation of NMDA receptors by endogenous zinc shapes dendritic function in cortical neurons.Cell reports · 2022Article
6 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
11 authors at 4 institutions in 1 country.
Funding
Abstract
Zinc is abundant in the central nervous system and regulates pain, but the underlying mechanisms are unknown. In vitro studies have shown that extracellular zinc modulates a plethora of signaling membrane proteins, including NMDA receptors containing the NR2A subunit, which display exquisite zinc sensitivity. We created NR2A-H128S knock-in mice to investigate whether Zn2+-NR2A interaction influences pain control. In these mice, high-affinity (nanomolar) zinc inhibition of NMDA currents was lost in the hippocampus and spinal cord. Knock-in mice showed hypersensitivity to radiant heat and capsaicin, and developed enhanced allodynia in inflammatory and neuropathic pain models. Furthermore, zinc-induced analgesia was completely abolished under both acute and chronic pain conditions. Our data establish that zinc is an endogenous modulator of excitatory neurotransmission in vivo and identify a new mechanism in pain processing that relies on NR2A NMDA receptors. The study also potentially provides a molecular basis for the pain-relieving effects of dietary zinc supplementation.
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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.