title: Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study.
abstract: OBJECTIVE
  Dysregulated biological stress systems and adverse life events, independently and in interaction, have been hypothesised to initiate chronic pain. We examine whether (1) function of biological stress systems, (2) adverse life events, and (3) their combination predict the onset of chronic multisite musculoskeletal pain.
  
  
  METHODS
  Subjects (n=2039) of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were identified using the Chronic Pain Grade Questionnaire and followed up for the onset of chronic multisite musculoskeletal pain over 6 years. Baseline assessment of biological stress systems comprised function of the hypothalamic-pituitary-adrenal axis (1-h cortisol awakening response, evening levels, postdexamethasone levels), the immune system (basal and lipopolysaccharide-stimulated inflammation) and the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, respiratory sinus arrhythmia). The number of recent adverse life events was assessed at baseline using the List of Threatening Events Questionnaire.
  
  
  RESULTS
  Hypothalamic-pituitary-adrenal axis, immune system and autonomic nervous system functioning was not associated with onset of chronic multisite musculoskeletal pain, either by itself or in interaction with adverse life events. Adverse life events did predict onset of chronic multisite musculoskeletal pain (HR per event=1.14, 95% CI 1.04 to 1.24, p=0.005).
  
  
  CONCLUSIONS
  This longitudinal study could not confirm that dysregulated biological stress systems increase the risk of developing chronic multisite musculoskeletal pain. Adverse life events were a risk factor for the onset of chronic multisite musculoskeletal pain, suggesting that psychosocial factors play a role in triggering the development of this condition.
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Generaal
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Vogelzangs
authors.affiliation: Musculoskeletal Research Collaboration (Epidemiology Group), University of Aberdeen, Aberdeen, UK.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Macfarlane
authors.affiliation: Department of Clinical and Health Psychology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Rinie
authors.initials: R
authors.lastname: Geenen
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Smit
authors.affiliation: Department of Biological Psychology and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Eco J C N
authors.initials: EJ
authors.lastname: de Geus
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands Department of Rehabilitation Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joost
authors.identifier: http://orcid.org/0000-0003-2027-0027
authors.initials: J
authors.lastname: Dekker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001008:Anxiety Disorders / Q000150:complications / Q000453:epidemiology; D001341:Autonomic Nervous System / Q000503:physiopathology; D059350:Chronic Pain / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D003866:Depressive Disorder / Q000150:complications / Q000453:epidemiology; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008016:Life Change Events; D008019:Life Style; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D059352:Musculoskeletal Pain / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D009426:Netherlands / Q000453:epidemiology; D010147:Pain Measurement / Q000379:methods; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D012307:Risk Factors; D013312:Stress, Physiological / Q000502:physiology*; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Epidemiology; Fibromyalgis/Pain Syndromes; Inflammation