Public Health and Epidemiology: Open Access
Autonomic Instability as a Systemic Signalling Disorder: A Hypothesis Linking Chronic Autonomic Dysregulation with Immune Modulation and Multisystem Symptom Expression
Abstract
Bruce H. Knox
Increasing evidence suggests that autonomic nervous system dysregulation plays a central role in the persistence of complex chronic symptom patterns following acute physiological insult. While autonomic disturbance is often considered within organ-specific contexts—cardiac arrhythmia, gastrointestinal motility disorders, or orthostatic intolerance—the broader systemic implications remain incompletely understood.
This hypothesis paper proposes that chronic autonomic instability functions as a signalling disorder that alters immune modulation, inflammatory tone, and visceral sensory processing across multiple physiological systems. Rather than representing isolated organ pathologies, persistent symptoms may arise from disrupted autonomic regulation of inter- system communication.
The proposed framework suggests that repeated physiological insults-including viral infection, haemodynamic compromise, and major surgical intervention—may progressively destabilise autonomic regulatory networks. This destabilisation may impair the cholinergic anti-inflammatory pathway, alter vagal signalling, and modify neuro-immune interactions.
Under this model, conditions such as chronic fatigue states, post-viral syndromes, gastrointestinal dysmotility, and unexplained inflammatory fluctuations may represent different phenotypic expressions of a shared regulatory disturbance rather than separate diseases.
The Knox Framework therefore proposes that chronic autonomic vulnerability should be considered a disease-modifying substrate capable of shaping systemic physiological responses over time. The hypothesis encourages further investigation of autonomic-immune coupling mechanisms and suggests that therapeutic approaches targeting autonomic stabilisation may offer broader systemic benefits.