The Informational Blackout: A Unified Bioenergetic and Active Inference Framework for Chronic Pain and Fatigue

Abstract Chronic pain and fatigue resist explanation under frameworks that treat them as localised dysfunctions of nociceptive or energetic circuitry. Their dissociation from tissue pathology, systematic co-emergence with autonomic dysregulation and circadian disruption, sex-stratified refractoriness to treatment, and resistance to single-mechanism pharmacological intervention collectively demand a higher-order explanatory architecture. We propose that both symptoms are the computationally optimal output of a predictive brain operating on structurally degraded interoceptive signals---a state we term the Informational Blackout. This state is defined by the simultaneous collapse of three interdependent systems. First, the structured zeitgeber network that evolved to provide temporally coherent afferent input to the brain's generative model is fragmented by the modern environment, which replaces a multidimensional, spectrally complete, and temporally progressing biological signal with a spectrally truncated, chromatically flat, and temporally static substitute. Second, the four-channel leptin informational network is silenced across its JAK/STAT transcriptional, endocannabinoid regulatory, synaptogenic, and ionic homeostasis channels by SOCS3-mediated multichannel transduction collapse---a state more precisely described as an informational blackout than as classical leptin resistance, because the failure is not a gain reduction in a single channel but the simultaneous interruption of four functionally distinct informational circuits through a common molecular gatekeeper. Third, the ionic setpoint of nociceptive and interoceptive circuits is driven to failure by five convergent molecular arms, all downstream of the same upstream condition: SOCS3--STAT3 transcriptional KCC2 suppression; microglial BDNF--TrkB--Src post-translational KCC2 inactivation; WNK1--SPAK ionic feedback consolidation; melatonin-deficiency-driven loss of the BDNF/ERK1/2 KCC2-restorative arm; and ECS disinhibition-driven CB1--cAMP--PKA KCC2 suppression. All five arms converge on the downregulation of the K+--Cl- cotransporter KCC2 and the consequent inversion of GABAergic inhibitory polarity. The functional inhibitory polarity of GABA depends on the NKCC1/KCC2 ratio rather than KCC2 alone; the five-arm architecture converges on a shift in this ratio, with KCC2 as the dominant regulated node.This five-arm ionic setpoint collapse constitutes the biophysical substrate of a Bayesian prior shift. A brain unable to verify its interoceptive predictions against coherent afferent signals, and constrained by elevated metabolic cost of prediction-updating under mitochondrial dysregulation, adopts high-confidence protective priors as the energetically parsimonious solution. This parsimony is computational rather than globally metabolic: chronic pain involves measurable hypermetabolism in salience and interoceptive networks, but the metabolic cost is redistributed from prediction-error correction subsystems toward fixed prior-maintenance circuits. Pain is the prior of structural vulnerability; fatigue is the prior of allostatic failure. Neither is an error. The framework generates falsifiable predictions that distinguish it from central sensitization and allostatic load models, identifies a composite biomarker strategy, and reorients therapeutic logic from nociceptive suppression toward the restoration of signal architecture. Keywords: chronic pain; fatigue; Long COVID; Informational Blackout; KCC2; NKCC1; SOCS3; active inference; leptin resistance; interoceptive precision; chronodisruption; metabolic integration.