{
  "abstract": "Neuropathic pain is frequently comorbid with anxiety and depression, yet the mechanisms linking immune signaling to affective brain circuits remain poorly understood. Here, we identify a neuroimmune circuit in which peripheral nerve injury activates microglia in the midbrain ventrolateral periaqueductal gray/dorsal raphe (vlPAG/DRN), triggering an NLRP3–IL‐1β‐dependent inflammatory cascade. Direct optogenetic or chemogenetic activation of vlPAG/DRN microglia is sufficient to drive negative affective behaviors. We show that local VGLUT2+ glutamatergic neurons (vlPAG/DRNGlu) are the principal IL‐1R1–expressing targets; IL‐1β activates these neurons to drive anxiety‐ and depression‐like states. Conversely, microglia‐specific Nlrp3 deletion or local IL‐1R1 blockade prevents neuropathic pain–induced affective deficits. Furthermore, circuit mapping and functional manipulation reveal an excitatory vlPAG/DRNGlu to the bed nucleus of the stria terminalis (BNSTGABA) pathway that is both sufficient to induce and required to maintain the affective component of neuropathic pain. Together, our findings delineate a microglia–vlPAG/DRNGlu–BNSTGABA axis that translates peripheral injury into maladaptive emotional states, revealing a discrete neuroimmune circuit substrate for mood comorbidity in chronic pain.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology of First Affiliated Hospital and Liangzhu Laboratory School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou China",
    "NANHU Brain‐Computer Interface Institute Hangzhou China",
    "School of Public Health Hangzhou Medical College Hangzhou Zhejiang China",
    "Department of Anesthesiology Ningbo No. 2 Hospital Wenzhou Medical University Ningbo China",
    "MOE Frontier Science Center for Brain Science and Brain‐machine Integration State Key Laboratory of Brain‐machine Intelligence Zhejiang University Hangzhou China",
    "NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang Key Laboratory of Pain Perception and Neuromodulation Zhejiang University Hangzhou China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jing Yang"
    },
    {
      "affs": [
        0,
        4,
        5
      ],
      "name": "Bing‐Jie Tang"
    },
    {
      "affs": [
        2
      ],
      "name": "Jia‐Yi Li"
    },
    {
      "affs": [
        0,
        4,
        5
      ],
      "name": "Shu‐Lan Xie"
    },
    {
      "affs": [
        0,
        4,
        5
      ],
      "name": "Shumin Duan"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Junping Chen",
      "orcid": "0000-0002-6268-719X"
    },
    {
      "affs": [
        0
      ],
      "name": "Shengmei Zhu",
      "orcid": "0000-0002-1877-9812"
    },
    {
      "affs": [
        0,
        1,
        4,
        5
      ],
      "name": "Zhen‐Zhong Xu",
      "orcid": "0000-0001-6578-211X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7s8zzve4khn3a.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.77071",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13460408/",
  "id": "7s8zzve4khn3a",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.77071",
  "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",
      "Research Article"
    ],
    [
      "openalex",
      "2737|Pain Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7202178159",
  "pdf_url": null,
  "pmcid": "PMC13460408",
  "pmid": "42579561",
  "published": "2026-08-11",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/7s8zzve4khn3a.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:23:11Z",
      "native_id": "PMC13460408",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.77071"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Pain Mechanisms and Treatments",
      "subfield": "physiology"
    }
  ],
  "title": "VlPAG/DRN Microglia Drive Neuropathic Pain‐Induced Depression via a Defined Neuroimmune Axis",
  "title_text": "VlPAG/DRN Microglia Drive Neuropathic Pain‐Induced Depression via a Defined Neuroimmune Axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:30Z",
  "url": "https://research.draconitic.com/paper/7s8zzve4khn3a",
  "venue": "Advanced Science",
  "versions": []
}