ArticleJournal of neuroinflammation2021
Downregulation of metallothionein-2 contributes to oxaliplatin-induced neuropathic pain.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 26 citations in OpenAlex.
- Zinc homeostasis imbalance: Potential therapeutic value in neurodegenerative diseases.Neural regeneration research · 2026Article
- Endothelial-Targeted Metallothionein-2 shRNA Nanoparticles Alleviate Migraine-Like Symptoms.CNS neuroscience & therapeutics · 2025Article
- Oxaliplatin-induced neuropathic pain in cancer: animal models and related research progress.Frontiers in pharmacology · 2025Review
- MIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study.International journal of molecular sciences · 2024Article
- NMDA Receptors Regulate Oxidative Damage in Keratinocytes during Complex Regional Pain Syndrome in HaCaT Cells and Male Rats.Antioxidants (Basel, Switzerland) · 2024Article
- Monoclonal Antibody Targeting CGRP Relieves Cisplatin-Induced Neuropathic Pain by Attenuating Neuroinflammation.Neurotoxicity research · 2024Article
- Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes.Frontiers in molecular neuroscience · 2024Article
- Article
- Ozone promotes macrophage efferocytosis and alleviates neuropathic pain by activating the AMPK/Gas6-MerTK/SOCS3 signaling pathway.Frontiers in immunology · 2024Article
- Lumbosacral spinal proteomic changes during PAR4-induced persistent bladder pain.Neuroscience letters · 2024Article
- Article
- Pancreatic Ductal Adenocarcinoma Induces Neural Injury that Promotes a Transcriptomic and Functional Repair Signature by Peripheral Neuroglia.Research square · 2023Article
- Animal models of chemotherapy-induced peripheral neuropathy for hematological malignancies: A review.Ibrain · 2023Review
- Positive interaction between GPER and β-alanine in the dorsal root ganglion uncovers potential mechanisms: mediating continuous neuronal sensitization and neuroinflammation responses in neuropathic pain.Journal of neuroinflammation · 2022Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWe previously reported a correlation between small doses of oxaliplatin penetrating onto the spinal cord and acute pain after chemotherapy. Here, we propose that MT2 within the spinal dorsal horns participates in the development of oxaliplatin-induced neuropathic pain and may be a pharmacological target for the prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN).
methodsThe rat model of CIPN was established by 5 consecutive injections of oxaliplatin (0.4 mg/100 g/day). Genetic restoration of neuron-specific metallothionein-2 was implemented 21 days before oxaliplatin treatment, and also, genetic inhibition by metallothionein-2 siRNA was performed. Mechanical allodynia and locomotor activity were assayed. Cell-specific expression of metallothionein-2, the mRNA levels of pro-inflammatory cytokines, nuclear translocation of NF-κB, the protein levels of expression of IκB-α, and interaction between IκB-α and P65 were evaluated in the spinal dorsal horns. Also, in vitro interaction of sequentially deleted IκB-α promoter with metallothionein-2 was used to assess the signal transduction mechanism.
resultsWe found that oxaliplatin induced downregulation of metallothionein-2 in rat spinal cord neurons. By contrast, genetic restoration of metallothionein-2 in the spinal dorsal horn neuron blocked and reversed neuropathic pain in oxaliplatin-treated rats of both sexes, whereas genetic inhibition of metallothionein-2 triggered neuropathic pain in normal rats. Overall locomotor activity was not impaired after the genetic alterations of metallothionein-2. At the molecular level, metallothionein-2 modulated oxaliplatin-induced neuroinflammation, activation of NF-κB, and inactive transcriptional expression of IκB-α promoter, and these processes could be blocked by genetic restoration of metallothionein-2 in the spinal dorsal horn neurons.
conclusionsMetallothionein-2 is a potential target for the prevention and treatment of CIPN. A reduction of NF-κB activation and inflammatory responses by enhancing the transcription of IκB-α promoter is proposed in the mechanism.
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