Investing Fascia Fibrosis and the "Mechano-Autonomic-Limbic-Immune" Network Hypothesis: A Unified Biomechanical Framework for Eleven Functional Somatic Syndromes

Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), migraine, irritable bowel syndrome (IBS), postural orthostatic tachycardia syndrome (POTS), chronic low back pain (cLBP), dry eye disease, anxiety disorders, major depressive disorder, and cognitive dysfunction ("brain fog") are eleven highly comorbid, symptom-overlapping, and etiologically unexplained functional somatic syndromes. These conditions are often collectively referred to in the literature as functional somatic syndromes. Although each disorder has its own distinct pathophysiological hypotheses, existing models have failed to fully explain why these conditions share a core symptom cluster of fatigue, autonomic dysregulation, cognitive impairment, emotional disturbance, pain, and ocular surface discomfort. Based on the anatomical characteristics, innervation patterns, and biomechanical properties of the investing fascia, this paper proposes the "mechano-autonomic-limbic-immune" network hypothesis. As used herein, the term "network" refers to a complex system of bidirectional coupling and positive-feedback closed-loop circuitry among four nodes—mechanics, autonomic function, limbic system, and immunity—distinct from unidirectional "pathways" or simple bidirectional "axes." The hypothesis suggests that multiple factors—including chronic forward head posture, persistent stress, viral infection, exposure to cold and damp environments, and poor dietary habits—may individually or synergistically drive fibrotic remodeling of the investing fascia with consequent loss of elastic buffering capacity. Abnormal shear stresses generated by daily head and neck micromovements may be transmitted through the three-layered collagen network of the deep cervical fascia to the carotid sheath, potentially affecting the core symptom clusters of these conditions through five downstream pathways. These five pathways include arterial compression, which may contribute to cerebral and ocular hypoperfusion (potentially driving migraine and cognitive dysfunction); venous compression, which may contribute to intracranial hypertension and glymphatic clearance impairment (potentially driving cognitive decline); impaired lymphatic drainage, which may contribute to impaired immune-metabolic waste clearance (potentially driving fatigue and widespread pain); sympathetic nerve stimulation, which may contribute to vasoconstriction and intraocular pressure fluctuations (potentially driving dry eye disease and anxiety); and vagus nerve compression, which may contribute to reduced parasympathetic tone and autonomic imbalance (potentially driving POTS, IBS, anxiety, and depression). The contribution of these five pathways varies across disorders. The arterial pathway predominantly contributes to migraine and cerebral hypoperfusion. The venous pathway predominantly contributes to cognitive decline secondary to glymphatic clearance impairment. The lymphatic pathway predominantly contributes to fatigue and pain secondary to immune-metabolic waste retention. The sympathetic pathway predominantly contributes to dry eye disease and anxiety (sympathetic component). The vagal pathway is broadly involved in the autonomic imbalance of POTS, IBS, anxiety, and depression. These five pathways converge at the brainstem nucleus tractus solitarius and, via the locus coeruleus-norepinephrine system and the hypothalamic-pituitary-adrenal axis, may respectively lead to dysfunction of the ascending reticular activating system (fatigue), limbic system disinhibition (emotional disturbance and cognitive decline), and central amplification of diffuse pain. Concurrently, postural compensation driven by fatigue, pain, and emotional disturbance, together with sympathetic and renin-angiotensin-aldosterone system activation, may—through both mechanically driven YAP signaling and biochemically driven Ang II→AT1R→YAP signaling—exacerbate investing fascial fibrosis in a closed "symptom-posture-fibrosis" positive-feedback vicious cycle. By relieving the abnormal mechanical load on the carotid sheath, investing fascia release may, in theory, simultaneously restore the normal function of all five pathways, thereby multitargetedly alleviating the core symptom clusters of the aforementioned disorders. Importantly, the five pathways do not operate in isolation. In most patients, the clinical phenotype arises from concurrent involvement and functional superposition of multiple pathways. For instance, POTS may involve synergistic contributions from the vagal pathway (reduced parasympathetic tone), the venous pathway (impaired cerebral blood flow regulation), and the sympathetic pathway (relative hyperactivity). Long COVID often manifests as co-sensitization of all five pathways to varying degrees. This multi-pathway superposition effect explains why the eleven disorders share extensive symptom overlap and high comorbidity, and provides the pathophysiological rationale for the "multitarget" intervention logic of investing fascia release—relieving a single upstream mechanical load may simultaneously reduce abnormal inputs across multiple pathways, achieving synergistic symptom relief. This paper proposes testable quantitative predictions and a three-phase validation framework, offering a testable theoretical perspective on the "cervicogenic mechanical driver" unifying mechanism for functional somatic syndromes.