{
  "abstract": "The external parabrachial nucleus (elPBN) contributes to diverse behaviors, including pain and stress. Neurons in this region use glutamatergic and neuropeptidergic signaling, with pituitary adenylate cyclase-activating polypeptide (PACAP) expressed in a subset of glutamatergic neurons. Deletion of PACAP in elPBN neurons attenuates behavioral responses to stress, but the contribution of PACAP to pain sensitization and of glutamatergic neurotransmission to pain- and stress-related responses remain poorly understood. Here, we show that constitutive loss of PACAP markedly attenuated nerve injury-induced hypersensitivity across heat, pressure, cold and tactile modalities without altering baseline nociception, while also reducing inflammation-induced spontaneous pain-related behavior. Notably, selective deletion of PACAP within elPBN neurons phenocopied the suppression of injury-induced hypersensitivity, but left inflammation- induced pain-related behavior unaffected. Ex vivo optogenetic-assisted circuit mapping showed that activation of PACAP-expressing elPBN terminals elicited glutamatergic transmission onto central amygdala (CeA) PKC{delta}-expressing neurons. Selective deletion of VGluT2 in elPBN neurons reduced nerve injury-induced hypersensitivity but, unlike PACAP deletion, also reduced inflammation-induced pain-related behavior, while leaving stress-induced hypophagia intact. Together, these findings reveal differential requirements for PACAP and glutamatergic neurotransmission within the elPBN across pain- and stress-related behaviors.",
  "abstract_shown": true,
  "affiliations": [
    "National Institutes of Health"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "S. Singh"
    },
    {
      "name": "S. Z. Jiang"
    },
    {
      "name": "W. J. F. Rosado"
    },
    {
      "name": "W. Brancaleone"
    },
    {
      "name": "D. C. Rolon"
    },
    {
      "name": "H. Tejeda"
    },
    {
      "name": "L. E. Eiden"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Carrasquillo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4pskhz95r2bpq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.07.755626",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.755626v1.full",
  "id": "4pskhz95r2bpq",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.755626v1",
  "language": null,
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2737|Pain Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7221445600",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.755626v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4pskhz95r2bpq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:09Z",
      "native_id": "10.64898/2026.10.07.755626",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.755626v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Differential utilization of PACAP and glutamate in parabrachial neurons shapes pain and stress",
  "title_text": "Differential utilization of PACAP and glutamate in parabrachial neurons shapes pain and stress",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:09Z",
  "url": "https://research.draconitic.com/paper/4pskhz95r2bpq",
  "venue": "bioRxiv",
  "versions": []
}