S1 Materials -

<div><p>Pain-o-metry provides biomarkers indicating connections between pain-related conditions and the health of various physiological systems, including the cardiovascular system. In this study, a non-linear data-driven analytical technique was employed to analyze second-by-second hemodynamic responses to recurrent clino-orthostatic challenges in 43 female fibromyalgia patients and 38 healthy women. The primary goal was to elucidate the systemic and systematic interaction of diverse hemodynamic and cardiovascular mechanisms across various timeframes and phases, precisely identifying their collective role as a unified bodily mechanism in managing regular gravity-induced blood redistribution challenges within the context of chronic pain. Findings suggest a connection between chronic disease and the equilibrium between cardiac preload and afterload in blood pressure regulation. Patients exhibit a shift towards afterload due to deficiencies in mechanisms governing initial transient reactions and later steady-state processes related to acutely induced blood redistributions. The imbalance is linked to reduced venous blood return, increasing cardiac strain—particularly in terms of contractility and heart rate—as the body compensates for heightened cardiac afterload and reduced effective blood volume. This makes individuals more susceptible to chronic peripheral tissue and cerebrovascular hypoperfusion, potentially leading to chronic ischemia and inflammation in various tissues and organs. The data-driven analytical technique enables the identification of combinations of gravity-induced hemodynamic and cardiovascular responses within specific timeframes for precise detection. This approach aims to facilitate potential diagnostic and monitoring applications in wearable devices, enhancing the ability to identify at-risk populations for preventive interventions.</p></div>