743: Quarterly Sleep-Pain Coupling in Knee Pain: Pain-to-Sleep Dominance and NAcc-Gated Sleep-to-Pain

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, Assessment and Measurement of Pain/Nociception, Quantitative Sensory testing (static and dynamic, e.g., HPT, PPT, CPM, TSP, offset analgesia), Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Sleep and pain are bidirectionally related, yet despite consistent day-to-day evidence, within-person dynamics at longer timescales remain poorly understood. We examined bidirectional sleep–pain coupling quarterly in adults from a knee pain study, and tested whether baseline pain-evoked brain activation in a priori regions moderated this coupling.

Methods: Adults from a knee pain study (N = 229; up to 11 quarterly time points) completed numerical rating scales for pain and sleep; eight pain items were factor-analyzed into general severity and a knee-versus-body contrast. A Bayesian hierarchical bivariate model with person-specific coupling slopes was fit. In a subset with baseline pain-evoked fMRI (n = 174), we tested whether activation in six a priori regions previously linked to sleep-deprivation-induced pain amplification, as well as the anterior cingulate cortex (ACC; tested separately based on preclinical evidence that ACC and nucleus accumbens [NAcc] are parallel dopaminergic-gated nodes), moderated sleep-to-pain coupling. In the pain-to-sleep direction, we tested five preclinically identified pain–arousal relay nodes as moderators using fMRI and grey matter volume.

Results: Population-level pain-to-sleep coupling was credibly negative, indicating the dominant direction, with substantial between-person heterogeneity; this was the only direction whose inclusion improved out-of-sample prediction. Quarters in which pain was more knee-dominant than a person's average predicted lower subsequent sleep quality, independent of overall pain severity. Although population-level sleep-to-pain coupling was not credible, the left NAcc credibly moderated this coupling, with credible coupling only in individuals with weaker or negative left NAcc responses. All six a priori regions showed moderation in the predicted direction—a pattern unlikely by chance. Pain-evoked ACC activation also credibly moderated sleep-to-pain coupling in the same direction. The pain-to-sleep moderation analysis yielded no credible effect.

Conclusions: Pain-to-sleep coupling dominates quarterly, reversing the asymmetry typically reported at the day-to-day timescale. Baseline pain-evoked activity in the left NAcc and ACC identifies individuals whose sleep quality has downstream consequences for pain, supporting a dopaminergic-gated trait-level vulnerability to sleep-driven pain amplification.

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Presenting Author: Pedro A Valdes-Hernandez
Submitting Author: Pedro Valdes Hernandez

Senior Author: Yenisel Cruz-Almeida

IASP 2026 Global Year theme of Neuropathic Pain: No

• Pedro A Valdes-Hernandez: PhD - University of Florida
• Soamy Montesino-Goicolea: MD - University of Florida
• Xiaohan Li: NA - University of Florida
• Eric Weber - University of Florida
• Angela Mickle - University of Florida
• Roland Staud: MD - University of Florida
• Kimberly T Sibille: PhD - University of Florida
• Burel R Goodin: PhD - Washington University in St. Louis
• Roger Fillingim: PhD - University of Florida
• Yenisel Cruz-Almeida: MSPH, PhD - University of Florida