Pain-stress interactions in musculoskeletal pain : study protocol of the ‘Stress in Pain’ (STRAIN) study

Background and aims: Stress and pain systems are known to interact. However, extensive research on the (dys)function of the stress system and its relationship with pain is lacking. Therefore, this study aimed to comprehensively characterize this relationship and to elucidate whether and how their interaction confers increased vulnerability for pain chronification. Methods: A study with a cross-sectional and a longitudinal arm will be performed to compare stress system (dys)functioning and its interaction with pain processing between musculoskeletal pain groups with varying pain duration and extent: chronic widespread pain (fibromyalgia), chronic localized pain (low back pain), subacute localized pain (low back pain) and pain-free controls (n=35/group). Localized pain groups will be reassessed after 6 months to characterize pain trajectory. Self-reported and (psycho)physiological assessments of pain (quantitative sensory testing [QST]) and stress will be conducted. To characterize neural responses, fMRI will be performed during heat pain stimulation combined with anticipatory cues and during a temporal summation protocol. Correlations between pattern expressions of the neurological pain signature (NPS) and stress markers will be analysed, and how this relationship differs between groups and over time will be examined. Results: The study is funded by the Research Foundation – Flanders (FWO) (G072323N) and awaiting ethical approval. Participant recruitment and data collection are anticipated to start in January 2025. Conclusions: The study will provide fundamental insights into neurophysiological mechanisms underlying the stress-pain relationship. We expect altered NPS pattern expressions and QST outcomes in pain groups compared to controls, which correlate with stress system (dys)functioning and can help characterize pain trajectories.