{
  "abstract": "Oxaliplatin-induced peripheral neuropathy (OIPN) is a major dose-limiting adverse effect of chemotherapy, and dorsal root ganglion (DRG) neurons are its principal targets. Although pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1 receptor signaling has been implicated in neuropathic pain, its contribution to the oxaliplatin-induced hyperexcitability of primary sensory neurons remains unknown. We used a dual-axis multi-electrode array (MEA) platform quantifying the total spike count (TSC) and synchronous spike ratio (SSR), indices of overall activity and coordinated firing. Short-term oxaliplatin exposure produced concentration-dependent increases in TSC and SSR in cultured DRG neurons, which were significantly attenuated by the selective PAC1 receptor antagonist, PA-810-04. Similarly, conditioned medium from oxaliplatin-treated satellite glial cell (SGC)-enriched cultures increased TSC and SSR in naïve DRG neurons, and these effects were suppressed by PA-810-04. Exogenous PACAP alone increased TSC concentration-dependently, with only a modest effect on SSR, as a positive control. These findings identify a PA-810-04-sensitive component of early oxaliplatin-induced hyperexcitability in primary sensory neurons, while the proposed neuron–glia mechanism remains hypothetical. They also provide a quantitative in vitro approach for investigating neuron–glia interactions in early OIPN and evaluating PAC1-targeted candidates.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan",
    "Department of Pharmacy, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan",
    "Department of Oral Anatomy and Cell Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan",
    "Laboratory of Pharmacology, Graduate School of Pharma-Medical Sciences, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan",
    "Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Taiyo Arima"
    },
    {
      "affs": [
        1
      ],
      "name": "Kazuhiro Takahama"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kimitaka Suetsugu",
      "orcid": "0009-0003-9719-7240"
    },
    {
      "affs": [
        0
      ],
      "name": "Yukiko Kobae"
    },
    {
      "affs": [
        2
      ],
      "name": "Haruki Iwai",
      "orcid": "0000-0002-2698-3522"
    },
    {
      "affs": [
        3
      ],
      "name": "Ichiro Takasaki",
      "orcid": "0000-0002-6083-1119"
    },
    {
      "affs": [
        4
      ],
      "name": "Takashi Kurihara",
      "orcid": "0000-0003-4001-6771"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hideyuki Terazono",
      "orcid": "0000-0002-2657-4454"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fwr4s3xx2kq6y.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219665",
  "fulltext_url": null,
  "id": "fwr4s3xx2kq6y",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9665",
  "language": null,
  "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": [
    [
      "openalex",
      "2737|Pain Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7224100323",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/fwr4s3xx2kq6y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:58Z",
      "native_id": "10.3390/ijms27219665",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9665"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Pain Mechanisms and Treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Selective PAC1 Receptor Antagonist, PA-810-04 Attenuates Oxaliplatin-Induced Hyperexcitability and Coordinated Firing in Cultured Dorsal Root Ganglion Neurons",
  "title_text": "Selective PAC1 Receptor Antagonist, PA-810-04 Attenuates Oxaliplatin-Induced Hyperexcitability and Coordinated Firing in Cultured Dorsal Root Ganglion Neurons",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:58Z",
  "url": "https://research.draconitic.com/paper/fwr4s3xx2kq6y",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}