Physiological framework for non-invasive detection and objective nociception activity in communicative patients: a...

Pain assessment in both communicative and non-communicative patients remains a major clinical challenge due to the inherently subjective nature of conventional tools such as the Numeric Rating Scale (NRS). In this study, we introduce a physiologically grounded and objective index, $\Delta T=TS-TD$ , derived from fractional-order impedance modeling of nociceptive dynamics. Here, $TD$ represents the transduction, and $TS$ reflects the transmission. These components are extracted non-invasively using the Anspec-Pro device, which records skin bioimpedance in real-time. A positive $\Delta T$ indicates enhanced central excitability, while a negative value suggests dominant inhibition. In a case study of postoperative patients, we show that $\Delta T$ closely follows and often precedes subjective NRS scores, with correlation coefficients reaching up to 0.86 ( $p=0.002$ ). We also introduce a refined index, $\Delta T_{\text{dyn}}$ , which incorporates the trend and local variability of $\Delta T$ for improved temporal alignment with reported pain. To address the very limited dataset (three patients, nineteen intervals each), we implemented a data augmentation strategy based on autoregressive modeling of $\Delta T$ and transfer-function mapping to NRS. This approach enabled the generation of synthetic trajectories per patient, thereby enriching the dataset while maintaining physiological plausibility. Analyses of the augmented data revealed consistent lead-lag patterns, correlations, and Granger causality relationships between $\Delta T$ , $\Delta T_{\text{dyn}}$ , and NRS, suggesting that $\Delta T$ may serve both as an anticipatory biomarker of nociceptive activity and as a real-time index aligned with subjective pain reporting. Overall, these results provide proof-of-concept that the Anspec-Pro device can support objective, non-invasive nociceptive tracking in clinical environments.