Hypothalamic-pituitary-adrenal axis feedback sensitivity in different states of back pain

Psychoneuroendocrinology. 2019 Mar;101:60-66. doi: 10.1016/j.psyneuen.2018.10.026. Epub 2018 Oct 26.


Pain normally signals a threat to bodily integrity and causes emotional distress. Acute pain serves a protective function, yet, when pain turns chronic, the protective function is lost. A chain of psychophysiological alterations including changes in the stress regulation system, apparent in dysfunctional activity and responsivity of the hypothalamic-pituitary-adrenal (HPA) axis, might be an important factor in this context. Moreover, maladaptive responses may be complicated by affective comorbid symptoms such as anxiety and depression, and alter nociceptive processing. However, the relationship among pain chronicity, stress regulation, and contributing components of comorbid symptomatology as well as somatosensory profiles has rarely been examined. In the present study, we obtained diurnal cortisol profiles at baseline and feedback regulation (following a dexamethasone suppression test (DST)) in subacute (SABP) and chronic (CBP) back pain patients and healthy control individuals (HC). We also assessed anxiety, depression and chronic stress levels and used quantitative sensory testing (QST) to detect sensory abnormalities. We found a hyper-suppression of cortisol following DST and thus enhanced negative stress feedback sensitivity in SABP compared to both CBP and HC. In SABP, DST-related cortisol levels were negatively associated with pain intensity, mediated by cold pain thresholds and anxiety. These data support a stress model of pain chronicity and suggest that stress responses might be indicators of individual vulnerability in the transition period of subacute pain.

Keywords: Chronic; Cortisol; Pain; Stress; Subacute.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / psychology
  • Anxiety Disorders / physiopathology
  • Back Pain / physiopathology*
  • Depression / psychology
  • Depressive Disorder / physiopathology
  • Dexamethasone / pharmacology
  • Female
  • Humans
  • Hydrocortisone / analysis
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Middle Aged
  • Pain / metabolism
  • Pain / physiopathology
  • Pain Threshold / psychology*
  • Pituitary-Adrenal System / physiopathology
  • Saliva / chemistry
  • Stress, Physiological / physiology*
  • Stress, Psychological / physiopathology


  • Dexamethasone
  • Hydrocortisone