Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a six-year cohort study

Background Dysregulated biological stress systems and adverse life events, both independently and in interaction, have been hypothesized to initiate chronic pain.

Objectives We examine whether (i) function of biological stress systems, (ii) adverse life events, and (iii) their combination predict the onset of chronic multi-site musculoskeletal pain.

Methods Subjects (n=2039) of the Netherlands Study of Depression and Anxiety, free from chronic multi-site musculoskeletal pain at baseline, were identified using the Chronic Pain Grade Questionnaire and followed-up for the onset of chronic multi-site musculoskeletal pain over 6 years. Baseline assessment of biological stress systems comprised function of the hypothalamic-pituitary-adrenal (HPA)-axis (1-h cortisol awakening response, evening levels, post-dexamethasone levels), the immune system (IMS; basal and lipopolysaccharide-stimulated inflammation) and the autonomic nervous system (ANS; heart rate, pre-ejection period, standard deviation of the normal-to-normal interval, respiratory sinus arrhythmia). The number of recent adverse life events were assessed at baseline using the List of Threatening Events Questionnaire.

Results HPA-axis, IMS and ANS functioning was not associated with onset of chronic multi-site musculoskeletal pain, either by itself or in interaction with adverse life events. Adverse life events did predict onset of chronic multi-site musculoskeletal pain.