Disrupted Biotensegrity in the Fiber Cellular Fascial Network and Neuroma Microenvironment: A Conceptual Framework...

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.