Abstract
BackgroundStudies 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.MethodsData 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).ResultsIn 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.ConclusionsOur 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.
Highlights
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
Because depressive and anxiety disorders have previously been associated with hypercortisolemia [31], we subsequently examined the association between cortisol and chronic pain, free from any depression/anxiety effects
HPA-axis function and chronic multi-site musculoskeletal pain without/with depression and anxiety This study found hypoactive HPA-axis function in chronic multi-site musculoskeletal pain (Table 2), while depressive and some types of anxiety disorders have previously been associated with hypercortisolemia [31,32], in the Netherlands Study of Depression and Anxiety (NESDA) study [33,34]
Summary
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. Some studies found increased salivary cortisol levels to be associated with higher pain severity scores among subjects with chronic widespread pain [27,28]. Other studies found decreased cortisol activity and reactivity to be associated with higher pain severity among healthy controls [29] and among chronic pain patients [30]. One prospective study found that subjects with low morning and high evening salivary cortisol levels, indicative of a blunting of the diurnal cortisol rhythm, and increased levels of serum cortisol after the dexamethasone suppression test (DST), indicative of a failure to suppress the HPA-axis, were more likely to develop new-onset chronic widespread pain [24]
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