{
  "abstract": "Background: Lidocaine‐containing teething gels are commonly used for pediatric oral analgesia, yet excessive exposure may induce severe neurotoxic effects, including seizure‐related events. The molecular mechanisms underlying lidocaine‐associated neurotoxicity remain poorly defined.\n\nMethods: We employed an integrative systems toxicology approach combining network toxicology, transcriptomic analysis (GSE143272), weighted gene co‐expression network analysis, molecular docking, molecular dynamics simulation, and experimental validation using Kamistad Gel extract at defined lidocaine‐equivalent concentration to characterize the molecular basis of lidocaine‐induced neurotoxicity.\n\nResults: Sixteen shared targets were identified through the integration of lidocaine‐related targets, epilepsy‐associated genes, and transcriptomic signatures. AKT1 and PTGS2 emerged as key hub genes. Functional analyses consistently suggested neuroinflammatory signaling, mitochondrial dysfunction, and synaptic dysregulation as major pathogenic mechanisms. Molecular docking and 10‐ns molecular dynamics simulations indicated stable interactions between lidocaine and AKT1/PTGS2. ROC analysis indicated moderate predictive performance of these genes in epilepsy datasets. In SH‐SY5Y cells, Kamistad Gel extract significantly increased AKT1 and PTGS2 expression, supporting activation of inflammation‐related neurotoxic pathways.\n\nConclusions: Lidocaine‐associated neurotoxicity may involve an AKT1/PTGS2‐centered neuroinflammatory–mitochondrial crosstalk network accompanied by synaptic dysfunction. This study provides a systems‐level mechanistic insight into lidocaine neurotoxicity and identifies potential targets for improving the safety of pediatric lidocaine‐containing formulations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, the First Dongguan Affiliated Hospital Guangdong Medical University Dongguan Guangdong China",
    "Dongguan Innovation Institute The First Dongguan Affiliated Hospital, Guangdong Medical University Dongguan Guangdong China",
    "Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics The First Dongguan Affiliated Hospital, Guangdong Medical University Dongguan China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Min Jiang",
      "orcid": "0009-0008-2277-4601"
    },
    {
      "affs": [
        1
      ],
      "name": "Liping Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Jingyi Deng"
    },
    {
      "affs": [
        2
      ],
      "name": "Hangyu Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuqia Xie"
    },
    {
      "affs": [
        2
      ],
      "name": "Xueqin Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Weidong Liu",
      "orcid": "0009-0009-0457-9180"
    },
    {
      "affs": [
        2
      ],
      "name": "Suidong Ouyang",
      "orcid": "0000-0003-4262-7939"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7841w6xncs58d.bib",
  "cited_by": 0,
  "doi": "10.1002/cns.71218",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696985/",
  "id": "7841w6xncs58d",
  "issns": [
    "1755-5930",
    "1755-5949"
  ],
  "landing_url": "https://doi.org/10.1002/cns.71218",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2806|Anesthesia and Neurotoxicity Research"
    ]
  ],
  "openalex": "W7223692967",
  "pdf_url": "https://europepmc.org/articles/PMC13696985?pdf=render",
  "pmcid": "PMC13696985",
  "pmid": "42928984",
  "published": "2026-10-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/7841w6xncs58d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:14Z",
      "native_id": "PMC13696985",
      "source": "pmc",
      "url": "https://doi.org/10.1002/cns.71218"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928984",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928984"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Anesthesia and Neurotoxicity Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Systems Toxicology Indicates AKT1/PTGS2‐Centered Neuroinflammatory‐Mitochondrial Crosstalk in Lidocaine Associated Neurotoxicity",
  "title_text": "Systems Toxicology Indicates AKT1/PTGS2‐Centered Neuroinflammatory‐Mitochondrial Crosstalk in Lidocaine Associated Neurotoxicity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:13Z",
  "url": "https://research.draconitic.com/paper/7841w6xncs58d",
  "venue": "CNS Neuroscience & Therapeutics",
  "versions": []
}