{
  "abstract": "Background\n\nChronic migraine (CM) is a debilitating neurological disorder characterized by persistent trigeminovascular sensitization and neuroinflammation. While FK506-binding protein 51 (FKBP5) modulates spinal neuroinflammation in chronic pain, its specific role in trigeminovascular nociceptive processing and CM pathogenesis remains largely unknown.Methods\n\nWe used a nitroglycerin (NTG)-induced CM mouse model. Following RNA-sequencing (RNA-seq) of total RNA isolated from trigeminal nucleus caudalis (TNC) tissue lysates, target expression was validated via reverse transcription quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence. To establish causality, we used a neuron-specific CRISPR-Cas9 editing system for Fkbp5 knockout within the TNC, alongside pharmacological interventions using the specific FKBP5 antagonist SAFit2 and the nuclear factor kappa B (NF-κB) inhibitor PDTC. Migraine-like behaviors were evaluated using von Frey filaments, coupled with biochemical analyses of NF-κB cascade activation and trigeminovascular neuroinflammation.Results\n\nRNA-seq, RT-qPCR, Western blotting, and immunofluorescence consistently confirmed a marked upregulation of Fkbp5 mRNA and FKBP5 protein in the TNC of NTG-treated mice, predominantly localized to neurons. Concurrently, significant microglial and astrocytic activation was observed in the TNC. Both neuron-specific Fkbp5 knockout and pharmacological inhibition with SAFit2 significantly attenuated NTG-induced periorbital and hind paw mechanical allodynia. Furthermore, FKBP5 deficiency blunted the NTG-triggered phosphorylation of p65 and IκBα, effectively suppressing the downstream release of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as the upregulation of calcitonin gene-related peptide (CGRP) and c-Fos. Crucially, targeted blockade of the NF-κB cascade with PDTC recapitulated the protective behavioral and biochemical effects of FKBP5 deficiency.Conclusions\n\nWe demonstrate that neuronal FKBP5 is significantly associated with CM pathogenesis. FKBP5 sustains mechanical allodynia by activating the NF-κB-mediated neuroinflammatory cascade. Consequently, targeting FKBP5 represents a promising therapeutic strategy for CM.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, The Second Hospital & Clinical Medical School, Lanzhou University, Cuiying Gate, No. 82 Linxia Road, Chengguan District, Lanzhou, Gansu, 730000, China.",
    "School of Life Science and Technology & State Key Laboratory of Advanced Medical Materials and Device, ShanghaiTech University, No. 393 Middle Huaxia Road, Pudong District, Shanghai, 201210, China.",
    "Department of Neurology, Henan Medical Key Laboratory of Neurology, The First Affiliated Hospital of Henan Medical University, No. 88 Jiankang Road, Xinxiang, Henan, 453100, China.",
    "Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, No. 1279 Sanmen Road, Hongkou District, Shanghai, 200434, China.",
    "Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxuedong Road, Nanning, Guangxi, 530007, China.",
    "Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No. 55 Zhenhai Road, Siming District, Xiamen, Fujian, 361003, China.",
    "The Graduate School of Fujian Medical University, No. 1 Xuefu North Road, Minhou County, Fuzhou, Fujian, 350122, China.",
    "School of Life Science and Technology & State Key Laboratory of Advanced Medical Materials and Device, ShanghaiTech University, No. 393 Middle Huaxia Road, Pudong District, Shanghai, 201210, China. guanjs@shanghaitech.edu.cn.",
    "Department of Neurology, The Second Hospital & Clinical Medical School, Lanzhou University, Cuiying Gate, No. 82 Linxia Road, Chengguan District, Lanzhou, Gansu, 730000, China. w100yg@gmail.com.",
    "Headache Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China. w100yg@gmail.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Cheng Peng"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianhua Fan"
    },
    {
      "affs": [
        1
      ],
      "name": "Gang Zhou"
    },
    {
      "affs": [
        2
      ],
      "name": "Min Zhao"
    },
    {
      "affs": [
        3
      ],
      "name": "Tianxiao Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Tingting Cao"
    },
    {
      "affs": [
        5
      ],
      "name": "Jingyuan Zheng"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Zijuan Guo"
    },
    {
      "affs": [
        4
      ],
      "name": "Guining Liang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhenchang Zhang"
    },
    {
      "affs": [
        7
      ],
      "name": "Ji-Song Guan"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Yonggang Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dswbgm8ykb38q.bib",
  "cited_by": 0,
  "doi": "10.1186/s10194-026-02460-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13685152",
  "id": "dswbgm8ykb38q",
  "issns": [
    "1129-2369",
    "1129-2377"
  ],
  "landing_url": "https://europepmc.org/article/MED/42902147",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2738|Migraine and Headache Studies"
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  "openalex": "W7170105932",
  "pdf_url": "https://europepmc.org/articles/PMC13685152?pdf=render",
  "pmcid": "PMC13685152",
  "pmid": "42902147",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/dswbgm8ykb38q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:42Z",
      "native_id": "MED:42902147",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42902147"
    },
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      "first_seen": "2026-10-30T13:46:11Z",
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      "url": "https://doi.org/10.1186/s10194-026-02460-6"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Migraine and Headache Studies",
      "subfield": "psychiatry"
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  ],
  "title": "Targeting neuronal FKBP5 attenuates mechanical allodynia by suppressing NF-κB-mediated neuroinflammation in an NTG-induced chronic migraine mouse model.",
  "title_text": "Targeting neuronal FKBP5 attenuates mechanical allodynia by suppressing NF-κB-mediated neuroinflammation in an NTG-induced chronic migraine mouse model.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:11Z",
  "url": "https://research.draconitic.com/paper/dswbgm8ykb38q",
  "venue": "The journal of headache and pain",
  "versions": []
}