Central Sensitization as a High-Gain Attractor State: A Four-Route Systems Model of the Excitatory–Inhibitory Shift

This preprint presents Version 4.1 of the Four-Route Central Sensitization Framework: an integrated systems-theoretical model of central sensitization as a high-gain excitatory–inhibitory attractor state. Version 4.1 is a minor update of Version 4.0. Central sensitization is defined as a self-sustaining excitatory-dominant regulatory state in which aggregate excitatory drive exceeds inhibitory regulatory capacity. Four biologically distinct but functionally convergent routes organize this shift: neuroimmune and central histaminergic activation, glutamate–GABA dysregulation, stress–CRH–HPA-axis and autonomic dysregulation, and persistent peripheral nociceptive input. The model explains persistence through the reinforcing interaction between sustained route-specific input, reduced inhibitory capacity, endogenous maintenance, and progressive attractor stabilization. This provides a systems-level explanation for clinical heterogeneity, symptom fluctuation, variable treatment response, relapse tendency, and differences in reversibility. The framework includes a Wilson–Cowan-inspired minimal dynamical core, in which excitatory state E(t), inhibitory capacity I(t), route-specific input, and endogenous maintenance are represented as latent system-level variables. This formalization is intended as a phenomenological architecture rather than a complete molecular model. Regulatory State Profiling (RSP) is positioned as a dynamic diagnostic instrument. Rather than classifying patients by symptom burden alone, RSP characterizes route configuration, excitatory–inhibitory shift, inhibitory or recovery capacity, endogenous maintenance, peripheral contribution, and inferred attractor depth. The framework situates central sensitization as a specific instantiation of the broader Network Regulatory Disorders (NRD) framework. It provides a basis for mechanism-guided stratification, longitudinal monitoring, state-based intervention, and empirical testing of route dominance, state stability, treatment response, reversibility, and relapse tendency.