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Highlights in Pathophysiology of the Musculoskeletal System, 3rd Edition
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Highlights in Pathophysiology of the Musculoskeletal System, 3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 269

Special Issue Editors

Dr. Marta Anna Szychlinska

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Guest Editor
Department of Precision Medicine in Medical, Surgical and Critical Care (MEPRECC), University of Palermo, 90127 Palermo, Italy
Interests: cartilage tissue engineering; mesenchymal stem cells; osteoarthritis; articular cartilage morphology
Special Issues, Collections and Topics in MDPI journals
Dr. Rosario Barone

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Guest Editor
Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Human Anatomy and Histology, University of Palermo, 90133 Palermo, Italy
Interests: cell biology; physiology; exercise performance; nutition; sports science; morphology; pathopysiology
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanna Calabrese

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Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98168 Messina, Italy
Interests: regenerative biomaterials; bone tissue engineering; osteoconduction; osteoinduction; osteointegration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The musculoskeletal system is an organ system that provides support, shape, and stability, and enables the movement of joints in the human body. It mainly consists of bones, skeletal muscles, tendons, ligaments, intervertebral discs, and articular cartilage tissue, as well as their associated nerves and blood vessels. Due to their primary functions, they are by far the most commonly injured tissues in the body, and musculoskeletal disorders represent one of the most common health problems worldwide. During the past few decades, with the advancement of research and technology, much has been discovered concerning the pathophysiological knowledge of the musculoskeletal system. Novel molecular targets have been identified for therapeutic approaches. Innovative methodologies such as tissue engineering, regenerative medicine, gene therapies, drug delivery systems, microgravity conditions, and nutritional interventions have facilitated the development of our understanding of mechanisms of musculoskeletal disorders such as osteoarthritis, rheumatoid arthritis, sarcopenia, muscle wasting, osteoporosis, bone necrosis, and many others. 

In this Special Issue of the International Journal of Molecular Sciences, we focus our attention on the latest discoveries and developments in musculoskeletal system pathophysiology at a molecular level and provide a comprehensive update on the literature accessible to scientists in the field. Thus, we wish to invite investigators from basic, pathophysiological, and translational musculoskeletal system research or closely related disciplines to contribute original articles, reviews, communications, and conceptual papers.

Dr. Marta Anna Szychlinska
Dr. Rosario Barone
Dr. Giovanna Calabrese
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • musculoskeletal
  • skeletal
  • tendon
  • ligament
  • intervertebral
  • articular cartilage
  • osteoarthritis
  • rheumatoid arthritis
  • sarcopenia
  • muscle wasting
  • osteoporosis
  • bone necrosis
  • synovium
  • pain
  • inflammation

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Published Papers (1 paper)

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33 pages, 1490 KB  
Hypothesis
Disrupted Biotensegrity in the Fiber Cellular Fascial Network and Neuroma Microenvironment: A Conceptual Framework for “Phantom Limb Pain”
by Shiloh Plaut
Int. J. Mol. Sci. 2025, 26(17), 8161; https://doi.org/10.3390/ijms26178161 - 22 Aug 2025
Viewed by 113
Abstract
Among the leading etiologies of limb amputations are diabetes mellitus, alongside trauma and peripheral vascular disease conditions, whose complications are major indications for surgery, which can subsequently elicit chronic refractory postamputation pain. ‘Phantom limb pain’ (PLP) denotes pain that is perceived as occurring [...] Read more.
Among the leading etiologies of limb amputations are diabetes mellitus, alongside trauma and peripheral vascular disease conditions, whose complications are major indications for surgery, which can subsequently elicit chronic refractory postamputation pain. ‘Phantom limb pain’ (PLP) denotes pain that is perceived as occurring in an absent part of the limb following amputation. Even though it is a relatively common complication among amputees—with an estimated prevalence as high as ~80 percent—the underlying mechanisms of this puzzling condition remain poorly understood. Current theories predominantly emphasize the role of the nervous system and neuropsychopathology in the development of PLP. However, these neurocentric explanations are disputed and have not yet been translated into effective treatments or a definitive cure for the condition, nor have several notable anomalies been settled, which has prompted researchers to call for the exploration of alternative theories. The aim of this paper is to offer an alternative mechanical mechanism for explaining PLP and spontaneous phantom sensations. This work introduces a theoretical model for the mechanism of PLP, drawing on a recent study that proposed this model to explain fibromyalgia-type psychosomatic syndromes as disorders driven by overactive soft tissue myofibroblasts. The manuscript proposes a shift from purely neurocentric models of PLP to a framework where the extracellular matrix and connective tissue, specifically myofascial tissue and inflammatory myofibroblasts—which are often overlooked in research—take part in its pathogenesis. In this suggested model, surgical interventions disrupt the biomechanical stability of the fascio-musculoskeletal biotensegrity-like system, thus acting as a contributing factor in the chronic pain manifestation. The term ‘biotensegrity’ refers to the dynamic biomechanical behavior of a living system that is stabilized by compressive and tensile force elements, a characteristic quality of myofascial tissue. In this framework, abnormal extracellular matrix remodeling, driven by overactive peripheral myofibroblasts, and the concomitant mechanical effects exerted on sensory nerves embedded within the fascia and reaching the neuroma microenvironment contribute to the generation and perception of spontaneous PLP and phantom sensations. The interplay between abnormal extracellular matrix, the neuroma’s intrinsic excitability, as well as peripheral and central neurophysiological mechanisms, collectively provide a biophysical neuropathophysiological basis to help explain PLP. This offers a different unexplored perspective on a condition with poorly understood mechanisms. Full article
(This article belongs to the Special Issue Highlights in Pathophysiology of the Musculoskeletal System, 3rd Edition)
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