Sleep spindles reveal sexually dimorphic trajectories of long-term bodily pain: a large-scale secondary analysis with implications for clinical biomarker development

Sleep spindles fulfill a dynamic role in orchestrating sensory gating, yet little is known about their possible role in shaping long-term bodily pain. Drawing upon polysomnographic data from a large cohort (n = 5804; 52.3% female) of participants from the Sleep Heart Health Study, we mapped the impact of spindle features on the evolution of pain over a five-year assessment period using cumulative linked mixed effect models controlling for known confounders. A higher density [+1SD from mean] of slow-spindles (8-13 Hz) at baseline conferred protective benefits against worsening pain severity in females (67% less likely to report severe pain [5/5] at follow up and 19% greater likelihood of being pain free [1/5] at follow-up) but not males, whilst longer slow-spindle durations conferred protective benefits against severe pain at follow-up for males (66% less likely to report severe pain [5/5] and 21% more likely to report being pain free [1/5]) but not females. Fast spindles (13-18 Hz) exerted negligible influence on pain outcomes regardless of sex. When examining a reversal of pathways, baseline pain levels produced only modest alterations in spindle dynamics over time, supporting the interpretation of sleep's independent impact on pain. These sexually dimorphic patterns could illuminate the potential of spindle characteristics as prognostic biomarkers for pain trajectories, opening avenues for precision interventions in chronic pain management whilst beckoning further investigation into their mechanistic underpinnings.