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

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, Δ T = T S - T D , derived from fractional-order impedance modeling of nociceptive dynamics. Here, T D represents the transduction, and T S reflects the transmission. These components are extracted non-invasively using the Anspec-Pro device, which records skin bioimpedance in real-time. A positive Δ T indicates enhanced central excitability, while a negative value suggests dominant inhibition. In a case study of postoperative patients, we show that Δ 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, Δ T dyn , which incorporates the trend and local variability of Δ 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 Δ 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 Δ T , Δ T dyn , and NRS, suggesting that Δ 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.