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HYPOTHESIS AND THEORY article

Front. Physiol.

Sec. Integrative Physiology

Volume 16 - 2025 | doi: 10.3389/fphys.2025.1647334

This article is part of the Research TopicMechanical Forces in Health and Disease: A Mechanobiological PerspectiveView all 6 articles

Bio-tensegrity and Extracellular Matrix Disruption in the Pathogenesis of Persistent Post-Operative Pain: A Hypothesis

Provisionally accepted
  • 1Shaare Zedek Medical Center, Jerusalem, Israel
  • 2University of Nicosia, Nicosia, Cyprus

The final, formatted version of the article will be published soon.

Persistent post-operative pain (PPOP) is a significant and often debilitating outcome of invasive procedures, with prevalences ranging from 30% to 70% following certain types of surgery. Yet, despite high prevalences and ongoing rigorous research, the pathophysiological mechanisms underlying PPOP remain insufficiently understood. While neurobiological explanations such as nerve injury, peripheral and central sensitization, and neuroma formation have been proposed, theory-based treatments provide only limited relief, resulting in persisting pain and decreased quality of life for affected individuals. This paper presents a framework for the theoretical pathogenesis of PPOP based on a work published recently which offered a connective-tissue-based mechanobioneurological mechanism for the pathophysiology of functional psychosomatic pain syndromes (or "fibromyalgia-type syndromes”), framing fibromyalgia and PPOP as disorders whose mechanism is based in the extracellular matrix’s homeostasis drawing on continuum biomechanics. With its aetiology and mechanisms in dispute, fibromyalgia, which historically was regarded as a connective tissue disorder, has long been a medical mystery. The model offers a mechanistic explanation for ‘primary fibromyalgia syndrome’ as a non-autoimmune disease driven by overactivity of myofascial and interstitial myofibroblasts that sustain mechanical stress within the fascio-musculoskeletal system. Fascia is a hugely overlooked complex delicate viscoelastic and fiber-cellular tissue that extends throughout the human body at various depths and layers and constitutes a complex dynamic interconnected extensive network of connective tissue that undergoes a process of continuous remodeling and transmits and absorbs loads while exhibiting tensegrity-type qualities. Surgical interventions may disrupt biomechanical stability, inducing chronic pain and central neurophysiological aberrations. The model frames these conditions as disorders of interconnected neurobiological and biomechanical systems and opens a new avenue for research on the link between neurobiology and connective tissue.

Keywords: Connective Tissue, Extracellular Matrix, Fascia, fascial armoring, Models, Theoretical, Myofibroblasts, Pain, Postoperative, Psychosomatic Medicine

Received: 15 Jun 2025; Accepted: 30 Jul 2025.

Copyright: © 2025 Plaut. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Shiloh Plaut, Shaare Zedek Medical Center, Jerusalem, Israel

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