{
  "abstract": "Genetic and molecular studies increasingly explain anesthetic and analgesic responses at the level of defined conductances, neuronal populations, and injury states. Their clinical implications depend on distinguishing target engagement from changes in firing and, ultimately, from a measurable therapeutic effect. This review examines recent evidence linking sodium, potassium, calcium, and sensory transduction channels to pain and inhibitory receptor composition, chloride regulation, and arousal circuits to anesthesia. Selective NaV1.8 inhibition provides an unusually complete translational example, spanning channel pharmacology, recordings from human sensory neurons, and randomized postoperative trials. Nevertheless, residual firing during substantial NaV1.8 inhibition and divergent explanations of NaV1.7-null analgesia show why the effects of a drug cannot be inferred directly from a genetic phenotype. Structural studies now resolve anesthetic binding and gating mechanisms in GABAA, NMDA, and HCN1 channels, while circuit experiments distinguish emergence, immobility, and antinociception. Neuroimmune signaling extends beyond cytokine-driven excitation to include inhibitory synapse removal, sex-dependent cellular pathways, and active pain resolution. Chromatin regulation, RNA modification, and neuronal senescence can stabilize altered excitability after injury. Human ganglion and spinal cord atlases, Patch-seq, and sensory assembloids provide more relevant models for connecting these mechanisms across scales, although none substitute for clinical validation. We emphasize research published from 2021 onward, retaining foundational studies where they establish a causal mechanism. The resulting evidence supports cell- and state-specific intervention rather than a single molecular explanation of anesthesia or chronic pain and identifies practical requirements for translating genetic discovery into perioperative treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.",
    "Department of Biology, Duke University, Durham, NC 27708, USA.",
    "Department of Anesthesiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.",
    "Department of Anesthesiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zheng Liu",
      "orcid": "0000-0003-3264-7119"
    },
    {
      "affs": [
        1
      ],
      "name": "Tong Wang",
      "orcid": "0000-0003-2407-9828"
    },
    {
      "affs": [
        2
      ],
      "name": "Xinran He"
    },
    {
      "affs": [
        3
      ],
      "name": "Siyuan Song"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/419243bfz1ey6.bib",
  "cited_by": 0,
  "doi": "10.3390/genes17101283",
  "fulltext_url": "https://europepmc.org/articles/PMC13704193",
  "id": "419243bfz1ey6",
  "issns": [
    "2073-4425"
  ],
  "landing_url": "https://europepmc.org/article/MED/42938399",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Ion channel regulation and function"
    ]
  ],
  "openalex": "W7222185971",
  "pdf_url": "https://europepmc.org/articles/PMC13704193?pdf=render",
  "pmcid": "PMC13704193",
  "pmid": "42938399",
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/419243bfz1ey6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42938399",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42938399"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Ion channel regulation and function",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Genetic and Molecular Regulation of Neuronal Excitability in Anesthesia and Pain.",
  "title_text": "Genetic and Molecular Regulation of Neuronal Excitability in Anesthesia and Pain.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/419243bfz1ey6",
  "venue": "Genes",
  "versions": []
}