title: Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders.
abstract: BACKGROUND
  Studies on hypothalamic-pituitary-adrenal axis (HPA-axis) function amongst patients with chronic pain show equivocal results and well-controlled cohort studies are rare in this field. The goal of our study was to examine whether HPA-axis dysfunction is associated with the presence and the severity of chronic multi-site musculoskeletal pain.
  
  
  METHODS
  Data are from the Netherlands Study of Depression and Anxiety including 1125 subjects with and without lifetime depressive and anxiety disorders. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multi-site musculoskeletal pain. Subjects were categorized into a chronic multi-site musculoskeletal pain group (n = 471) and a control group (n = 654). Salivary cortisol samples were collected to assess HPA-axis function (awakening level, 1-h awakening response, evening level, diurnal slope and post-dexamethasone level).
  
  
  RESULTS
  In comparison with the control group, subjects with chronic multi-site musculoskeletal pain showed significantly lower cortisol level at awakening, lower evening level and a blunted diurnal slope. Lower cortisol level at awakening and a blunted diurnal slope appeared to be restricted to those without depressive and/or anxiety disorders, who also showed a lower 1-h awakening response.
  
  
  CONCLUSIONS
  Our results suggest hypocortisolemia in chronic multi-site musculoskeletal pain. However, if chronic pain is accompanied by a depressive or anxiety disorder, typically related to hypercortisolemia, the association between cortisol levels and chronic multi-site musculoskeletal pain appears to be partly masked. Future studies should take psychopathology into account when examining HPA-axis function in chronic pain.
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, PO Box 74077, 1070 BB Amsterdam, The Netherlands. e.generaal@ggzingeest.nl.
authors.forename: Ellen
authors.initials: E
authors.lastname: Generaal
authors.forename: Nicole
authors.initials: N
authors.lastname: Vogelzangs
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Macfarlane
authors.forename: Rinie
authors.initials: R
authors.lastname: Geenen
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Smit
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.forename: Joost
authors.initials: J
authors.lastname: Dekker
mesh_terms: D000368:Aged; D001008:Anxiety Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D059333:Central Nervous System Sensitization; D059350:Chronic Pain / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D002940:Circadian Rhythm; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D059352:Musculoskeletal Pain / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D009426:Netherlands / Q000453:epidemiology; D010147:Pain Measurement; D010913:Pituitary-Adrenal System / Q000378:metabolism* / Q000503:physiopathology; D011237:Predictive Value of Tests; D012463:Saliva / Q000378:metabolism*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D015415:Biomarkers; D006854:Hydrocortisone