Quarterly Sleep–Pain Coupling in Knee Pain: Pain-to-Sleep Dominance, Localization Dependence, and Reward-Circuit Moderation of Sleep-to-Pain Coupling
Year: 2026
Type: article
Study design: Observational Study
Abstract: Sleep-pain coupling is bidirectional, with consistent day-to-day evidence of asymmetry favoring sleep-to-pain effects, yet within-person dynamics at longer timescales remain poorly understood, despite directionality shaping which symptom clinicians should target first. We examined sleep-pain coupling quarterly over three years in 229 adults. Numerical rating scales captured past-week self-reported sleep quality and eight self-reported pain-related items-the latter were factor-analyzed into general severity and a knee-versus-body contrast. A Bayesian bivariate autoregression with correlated innovations and person-specific slopes was fit to within-person deviations. Pain-to-sleep coupling, but not sleep-to-pain coupling, was credible (95% credible interval excluding zero)-stronger self-reported pain was associated with next-quarter worse sleep-reversing the typical day-to-day asymmetry. Quarters in which pain was more knee-dominant showed stronger pain-to-sleep coupling. We also tested, under a theory-driven approach, neuroimaging-based predisposition markers of these couplings. A prior study identified brain regions, including the nucleus accumbens (NAcc), where pain-evoked activation tracked sleep-deprivation-induced next-day pain amplification. Preclinical evidence also implicates the anterior cingulate cortex (ACC) and NAcc as parallel dopaminergic-gated nodes. We therefore tested, in a subset (N=174), whether baseline pain-evoked fMRI activation in these regions moderated sleep-to-pain coupling as a possible trait-level marker. The left NAcc and the ACCs credibly moderated sleep-to-pain coupling, which were stronger at greater deactivation and credible in nearly all deactivating individuals. In the pain-to-sleep direction, testing five preclinical pain-arousal relay nodes (fMRI and gray matter volume) as moderators yielded no credible effect. PERSPECTIVE: In knee osteoarthritis, worse pain predicts worse sleep months later, but sleep does not predict pain, reversing the usual day-to-day asymmetry. Treating pain may more directly improve sleep, while baseline pain-evoked deactivation in reward and cingulate regions may identify whose pain instead follows sleep. Future trials should test both.
Source: Journal of Pain
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,180
Awards: Mechanisms of Oxytocins Analgesia in Older Adults, National High Magnetic Field Laboratory Renewal 2018-2022, G2294341347, G2336362177, G2386482098, Biobehavioral basis of knee osteoarthritis pain, Ethnic Differences in Responses to Painful Stimuli, G3265072488, G3330702905, G354028113, G3560959519, G410635398, G4624992917, Ethnic Differences in Responses to Painful Stimuli, G502564109, G502626589, National High Magnetic Field Laboratory Renewal 2013-2017, G6010147111, G6409167540, Health Disparities in Osteoarthritis: Biological Aging, Stress, and Pain - Modulation by Resilience Factors, Machine learning-based brain aging morphological signatures of chronic musculoskeletal pain
OpenAlex ID: W7220970950