{
  "abstract": "The nocebo effect, the evil twin of the better-known placebo effect, in which anticipation of harm worsens pain and other symptoms, is increasingly thought to be responsible for poor clinical outcomes. In humans, nocebo hyperalgesia (i.e., increased pain sensitivity) is blocked by proglumide, a cholecystokinin (CCK) receptor antagonist. Yet, the neural circuitry underlying nocebo hyperalgesia remains unidentified, largely due to a lack of appropriate animal models. Independently, our two laboratories developed unique animal models of CCK-dependent nocebo hyperalgesia in which the expectation of pain was elicited by environmental or social cues. We find that both nocebo paradigms share a neural circuit involving CCK release from neurons projecting from the anterior cingulate cortex to the lateral periaqueductal gray. This previously unrecognized pathway could represent a promising target for therapeutic interventions in pain-related disorders. One-Sentence Summary Pain expectations, whether environmentally conditioned or socially transmitted, are mediated by a shared neural circuit involving cholecystokinin (CCK) projections from the anterior cingulate cortex (ACC) to the lateral periaqueductal gray (PAG).",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychological and Brain Sciences, University of Toronto Mississauga, Mississauga, ON, Canada",
    "Department of Psychology, University of Toronto",
    "Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada",
    "Department of Psychology, McGill University, Montreal, QC, Canada",
    "Department of Psychology, McGill University",
    "Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada",
    "University of Toronto",
    "Department of Psychology, University of Toronto Mississauga",
    "Department of Cell and Systems Biology, University of Toronto",
    "Department of Psychology, Anesthesia, and Faculty of Dental Medicine, and Alan Edwards Centre for Research on Pain, McGill University",
    "Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada. jeffrey.mogil@mcgill.ca",
    "Department of Psychology, McGill University, Montreal, QC, Canada. jeffrey.mogil@mcgill.ca",
    "Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada. lj.martin@utoronto.ca",
    "Department of Psychological and Brain Sciences, University of Toronto Mississauga, Mississauga, ON, Canada. lj.martin@utoronto.ca"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sandra J. Poulson",
      "orcid": "0000-0002-5533-4599"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Aleksandrina Skvortsova",
      "orcid": "0000-0003-0512-0792"
    },
    {
      "affs": [
        5,
        1
      ],
      "name": "Fatama Tuz Zahra",
      "orcid": "0009-0007-4654-4061"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Damien C. Boorman",
      "orcid": "0000-0003-2819-1948"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Seyed Asaad Karimi"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Lisiê Valéria Paz",
      "orcid": "0000-0001-7259-9137"
    },
    {
      "affs": [
        0,
        8
      ],
      "name": "Wanning Cui"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Antonietta Mandatori",
      "orcid": "0009-0005-0548-896X"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Jacob Burek",
      "orcid": "0009-0004-5276-9812"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Zahra Siddiqi",
      "orcid": "0009-0001-4762-8140"
    },
    {
      "affs": [
        5,
        9
      ],
      "name": "Maryam I. Fazili",
      "orcid": "0009-0008-2697-6104"
    },
    {
      "affs": [
        0,
        8,
        7
      ],
      "name": "Shivani R Gami",
      "orcid": "0009-0005-1248-9362"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Oakley B. Morgan",
      "orcid": "0009-0002-3507-3552"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Mélanie Di Maria"
    },
    {
      "affs": [
        0
      ],
      "name": "Anton Dinh"
    },
    {
      "affs": [
        3
      ],
      "name": "Lianfang Liang"
    },
    {
      "affs": [
        3
      ],
      "name": "Robert Contofalsky",
      "orcid": "0009-0005-4907-4144"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Jeffrey S. Mogil",
      "orcid": "0000-0003-1359-5720"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "Loren J. Martin",
      "orcid": "0000-0003-0579-2441"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/de5xd799pp5tx.bib",
  "cited_by": 6,
  "doi": "10.1038/s41467-026-73266-y",
  "fulltext_url": null,
  "id": "de5xd799pp5tx",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-73266-y",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "2805|Pain Management and Placebo Effect"
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  "openalex": "W4407209192",
  "pdf_url": null,
  "pmcid": "PMC13381858",
  "pmid": "42161995",
  "published": "2026-05-20",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/de5xd799pp5tx.ris",
  "sources": [
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      "first_seen": "2026-10-30T13:26:53Z",
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      "url": "https://doi.org/10.1038/s41467-026-73266-y"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2805|Pain Management and Placebo Effect",
      "subfield": "neuroscience"
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  ],
  "title": "Cholecystokinin input from the anterior cingulate cortex to the lateral periaqueductal gray mediates nocebo pain behavior in mice",
  "title_text": "Cholecystokinin input from the anterior cingulate cortex to the lateral periaqueductal gray mediates nocebo pain behavior in mice",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:11Z",
  "url": "https://research.draconitic.com/paper/de5xd799pp5tx",
  "venue": "Nature Communications",
  "versions": []
}