{
  "abstract": "This hypothesis manuscript applies the Temporal Matrix Principle (TMP) and Microenvironmental Metric Deformation (MMD) framework to the persistence of fibromyalgia. It proposes that, in a subset of patients, previous biological perturbations may become encoded in fascia–muscle and interstitial microenvironments, leaving retained tissue states that influence small sensory fibers and interact with central amplification, autonomic regulation, and neuroimmune signaling.\n\nThe framework distinguishes four experimentally separable operations—Encoding, Retention, Readout, and Erasure—and introduces a peripheral microenvironmental state vector, M_FM(x,t). Candidate mechanisms include altered extracellular-matrix organization, persistent cellular tension, hydration and transport changes, microvascular dysfunction, and a specifically testable fibrinogen–fibrin provisional-matrix hypothesis.\n\nThe manuscript presents falsifiable predictions involving spatial co-localization, persistence after trigger withdrawal, experimental phenocopy, rescue, and selective normalization of retained material features. An accompanying evidence matrix distinguishes observations in fibromyalgia from experimental precedents in other systems and unvalidated mechanisms. A conceptual figure summarizes the proposed persistence loop.\n\nThis work is a hypothesis-generating contribution. It does not establish extracellular pathological memory, fibrin deposition, or a complete causal brain–body loop in fibromyalgia, and it does not propose a validated diagnostic test or treatment.\n\nVersion 2 — Revised hypothesis and experimental framework\n\nThis substantially revised manuscript examines whether a defined peripheral microenvironmental feature could contribute to persistent sensory dysfunction in a subgroup of patients with fibromyalgia.\n\nThe revision prioritizes disease-specific evidence, distinguishes competing immune, neuronal, vascular and extracellular mechanisms, and separates current environmental dependence from the stronger hypothesis of retained material history. It does not assume that fibromyalgia constitutes a universal matrix disorder or an autonomous feedback circuit.\n\nProposed experiments separate extracellular preparations, soluble factors and cellular origin through controlled comparisons, selective perturbation, reconstruction and independent validation. Interpretation criteria distinguish supporting, weakening and inconclusive findings, while clinical translation is considered separately from laboratory target engagement.\n\nVersion 2 includes an updated evidence matrix, 26 references and a new conceptual figure. The macrophage PIEZO1–NGF–neuronal TrkA pathway reported by Wu et al. in Science Immunology (2026; doi:10.1126/sciimmunol.aeb3809) is discussed as a mechanistic precedent from visceral-pain models, not as direct evidence in fibromyalgia. Its discussion is limited to the available abstract and editorial summary.\n\nThis work presents a hypothesis and selective narrative synthesis. It reports no new experimental data, is not a systematic review or meta-analysis, and establishes no diagnostic biomarker or treatment indication.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "name": "Christiano Gondim Moreira",
      "orcid": "0009-0001-6133-7403"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dxzdjsfbpjg2k.bib",
  "cited_by": 0,
  "doi": "10.5281/zenodo.23651997",
  "fulltext_url": null,
  "id": "dxzdjsfbpjg2k",
  "issns": [],
  "landing_url": "https://zenodo.org/records/23651997",
  "language": null,
  "licence": "CC-BY-SA-4.0",
  "licence_label": "CC BY-SA 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-sa/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dxzdjsfbpjg2k.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:20:56Z",
      "native_id": "23651997",
      "source": "zenodo",
      "url": "https://zenodo.org/records/23651997"
    }
  ],
  "subjects": [],
  "title": "Fibromyalgia as a Persistent Multiscale Tissue State: A Temporal Matrix Hypothesis Linking Peripheral Microenvironment, Small Fibers, and Central Sensitization",
  "title_text": "Fibromyalgia as a Persistent Multiscale Tissue State: A Temporal Matrix Hypothesis Linking Peripheral Microenvironment, Small Fibers, and Central Sensitization",
  "type": "preprint",
  "updated_at": "2026-11-08T12:20:56Z",
  "url": "https://research.draconitic.com/paper/dxzdjsfbpjg2k",
  "venue": "Zenodo",
  "versions": []
}