{
  "abstract": "Diabetic neuropathic pain (DNP) is a common and intractable complication of diabetes with limited therapeutic options. Distinct from traditional NF-κB or MAPK inflammatory pathways, resolvin D2 (RvD2) alleviates DNP through metabolic reprogramming—a novel mechanism that remains largely unexplored. Untargeted metabolomics analysis of the spinal cord from DNP model mice and RvD2-treated mice revealed significant alterations in fatty acid oxidation (FAO)-related metabolites between the two groups. Functionally, RvD2 effectively alleviated hyperalgesia in DNP mice and ameliorated the FAO dysfunction associated with a pro-inflammatory microglial state. Mechanistically, RvD2 upregulated the expression of peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1a (CPT1a), thereby activating the PPARα/CPT1a axis to enhance FAO. This metabolic shift consequently augmented ATP production, suppressed reactive oxygen species (ROS) levels, and diminished succinate accumulation, which in turn blocked hypoxia-inducible factor-1α (HIF-1α)-mediated pro-inflammatory signaling. Concurrently, RvD2 elevated the acetyl-CoA pool, promoting histone acetylation and chromatin accessibility at the promoters of pro-resolving polarization-related genes, which drove microglia toward a pro-resolving phenotype. Notably, the specific CPT1a inhibitor etomoxir partially reversed these protective effects of RvD2. In conclusion, RvD2 alleviates DNP by driving microglial pro-resolving polarization through a CPT1a-mediated metabolic-epigenetic axis, providing a promising therapeutic target and a potent candidate agent for the clinical management of DNP.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China",
    "Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; Shandong University, Jinan, Shandong, 250100, China",
    "Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; Corresponding author."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xinyi Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Xueying Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lutong Yue"
    },
    {
      "affs": [
        0
      ],
      "name": "Keyang Duan"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuchen Hao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xian'ge Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Tao Sun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2hgk88yac0v2r.bib",
  "cited_by": 0,
  "doi": "10.1016/j.neurot.2026.e01111",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S1878747926002813",
  "id": "2hgk88yac0v2r",
  "issns": [
    "1878-7479",
    "1933-7213"
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  "landing_url": "https://doi.org/10.1016/j.neurot.2026.e01111",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
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      "lcc",
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      "openalex",
      "2737|Pain Mechanisms and Treatments"
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  "openalex": "W7223697061",
  "pdf_url": "https://www.neurotherapeuticsjournal.org/article/S1878-7479(26)00281-3/pdf",
  "pmcid": "PMC13734923",
  "pmid": "42933061",
  "published": "2026-10-27",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/2hgk88yac0v2r.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T14:22:02Z",
      "native_id": "04a30672623247cd87e7d97ba07c27cd",
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      "url": "https://doi.org/10.1016/j.neurot.2026.e01111"
    },
    {
      "first_seen": "2026-11-09T12:20:43Z",
      "native_id": "PMC13734923",
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      "url": "https://doi.org/10.1016/j.neurot.2026.e01111"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Pain Mechanisms and Treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Exogenous resolvin D2 alleviates diabetic neuropathic pain by regulating microglial fatty acid metabolism and phenotypic polarization",
  "title_text": "Exogenous resolvin D2 alleviates diabetic neuropathic pain by regulating microglial fatty acid metabolism and phenotypic polarization",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:20:43Z",
  "url": "https://research.draconitic.com/paper/2hgk88yac0v2r",
  "venue": "Neurotherapeutics",
  "versions": []
}