Elucidating the interplay between salivary stress biomarkers and sleep disturbance in shaping the pain experience of youth with chronic pain

OA Version
Citation
Abstract
BACKGROUND: Chronic pain in youth is a major health concern, with a prevalence of 20.8% worldwide. Salivary biomarkers have been independently linked to chronic pain, where dehydroepiandrosterone (DHEA), a neuroendocrine hormone that plays a role in the physiological stress response, and C-reactive protein (CRP), an inflammatory marker are two biomarkers which will be examined. Sleep disturbances, stress, and stress-related pain outcomes are known to impact pain perception and intensify chronic pain symptoms. While DHEA and CRP in chronic pain are well studied, their combined impact on sleep interference and stress-related pain outcomes in adolescents remains unclear. This study aims to explore how salivary biomarkers of inflammation and stress regulation influence pain experiences and sleep disruption in youth with chronic pain. METHODS: Participants were recruited from Boston Children’s Hospital tertiary pain clinic, presenting with varying chronic pain conditions unrelated to musculoskeletal, pathological inflammation, or tissue injury. They were asked to provide salivary samples and completed baseline self-reported questionnaires measuring sleep disturbances, stress levels, pain-related outcomes, and pain intensity. Bivariate correlation analyses compared CRP and DHEA to sleep disturbances and self-reported pain-related outcomes of stress and pain catastrophizing. Following descriptive statistics, one-way ANOVAs were done between CRP, psychosocial stressor variables, and pain intensity. T-tests were performed between DHEA, psychosocial stressor variables, and pain intensity. RESULTS: The study analyzed 62 participants (ages 10-17; M age = 14.5) with chronic pain. Analysis revealed stress was significantly associated with greater sleep disturbances (r = 0.53, p = 0.001) and pain catastrophizing (r = 0.41, p = 0.024). Further one-way ANOVAs performed demonstrated statistically significant associations between stress and CRP tertiles. CRP showed negative associations with sleep disturbance and stress, but a positive association with pain catastrophizing. Data trends between DHEA and sleep disturbance indicated a negative association. Meanwhile, a positive association between high stress levels and elevated levels of pain catastrophizing. These findings were not statistically significant, which limits definitive conclusions. CONCLUSIONS: Notable associations were observed when comparing stress with sleep disturbances and pain catastrophizing. Lower CRP tertiles were found to have a significant association with higher stress levels. Pain catastrophizing also demonstrated significant association with usual pain intensity levels. Whereas, CRP did not show significant effects on sleep disturbances, or pain catastrophizing. DHEA did not have a significant influence on sleep disturbances, pain catastrophizing, or stress. These results highlight the impact of the stress-sleep relationship on the chronic pain experience in youth and a potential linkage existing in this relationship with inflammatory biomarker, CRP. This study was limited by a small sample size with minimal racial, ethnic, and gender diversity. Additionally, examining only two salivary biomarkers restricted the ability to fully capture the complexity of the pain experience. Future research is needed in a larger cohort, to clarify the role salivary biomarkers play in the interaction between sleep and stress in adolescents with chronic pain.
Description
2025
License
Attribution-NonCommercial-NoDerivatives 4.0 International