Authors
Carla Pandolfi-Cuadrado
Published in
Frontiers in pain research (Lausanne, Switzerland). Volume 7. Pages 1896306. Epub Aug 12, 2026.
Abstract
Chronic pain and fatigue have resisted pharmacological resolution for two decades despite detailed mechanistic characterisation of nociceptive circuits. This perspective argues that the problem is not insufficient data but a mismatch between the level at which the dominant model operates and the level at which chronification is decided. Central sensitisation describes how nociceptive circuits amplify their gain. It does not, on its own, explain why that amplification becomes permanent, why it co-emerges systematically with fatigue and autonomic dysregulation, or why its epidemiology is stratified by sex in ways that differ qualitatively rather than quantitatively. The Informational Blackout framework proposes that chronic pain and fatigue are not malfunctions but appropriate responses from a self-maintaining system that has lost the biological infrastructure on which it was built to depend. The upstream driver is structural degradation of the signal architecture by the modern environment, mediated through SOCS3-driven multichannel transduction collapse and a convergent five-arm ionic setpoint failure that inscribes pain as a stable engram. The framework is offered as an upstream extension of central sensitisation; it grades its own evidence explicitly and generates falsifiable predictions that reorient therapeutic logic from nociceptive suppression toward signal architecture restoration.
PMID:
42657219
Bibliographic data and abstract were imported from PubMed on 27 Aug 2026.
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