Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents

Abstract

In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latter, rather than the pain, might explain the HPA results. A population study ascertained pain and psychological status in subjects aged 25 to 65 years. Random samples were selected from the following three groups: satisfying criteria for chronic widespread pain; free of chronic widespread pain but with strong evidence of somatisation ('at risk'); and a reference group. HPA axis function was assessed from measuring early morning and evening salivary cortisol levels, and serum cortisol after physical (pain pressure threshold exam) and chemical (overnight 0.25 mg dexamethasone suppression test) stressors. The relationship between HPA function with pain and the various psychosocial scales assessed was modelled using appropriate regression analyses, adjusted for age and gender. In all 131 persons with chronic widespread pain (participation rate 74%), 267 'at risk' (58%) and 56 controls (70%) were studied. Those in the chronic widespread pain and 'at risk' groups were, respectively, 3.1 (95% CI (1.3, 7.3)) and 1.8 (0.8, 4.0) times more likely to have a saliva cortisol score in the lowest third. None of the psychosocial factors measured were, however, associated with saliva cortisol scores. Further, those in the chronic widespread pain (1.9 (0.8, 4.7)) and 'at risk' (1.6 (0.7, 3.6)) groups were also more likely to have the highest serum cortisol scores. High post-stress serum cortisol was related to high levels of psychological distress (p = 0.05, 95% CI (0.02, 0.08)). After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated. This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group. Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress.

Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders

“…No significant associations with chronic multi-site musculoskeletal pain were found for the dynamic of the cortisol awakening response (AUCi) and post-dexamethasone cortisol levels, which is in contrast to a previous study that demonstrated non-suppression of the HPA-axis in 131 subjects with chronic widespread pain by elevated serum cortisol levels after a 0.25 mg dexamethasone suppression test [25]. This opposite finding might be explained by heterogeneity of samples or measurement differences, e.g.…”

“…However, in support of our findings, a cross-sectional study by McBeth et al showed that a lower saliva cortisol score, composed of morning and evening cortisol levels, was associated with chronic widespread pain and being psychologically at risk of chronic widespread pain [25]. …”

“…in the assessment of pain, depression, anxiety and cortisol [55]. Moreover, as also suggested by the results of our study, adjusting for the effects of psychological distress might attenuate the association between post-stress cortisol levels and chronic multi-site musculoskeletal pain [25]. …”

No man is an island: Living in a disadvantaged neighborhood influences chronic pain development after motor vehicle collision

“…However, previous studies have not been able to directly test the hypothesis that low nSES affects adverse health outcomes by altering stress system function. In this study, a common genetic polymorphism near FKBP5 , a gene known to influence the function of the HPA axis [4; 6; 27; 39; 49; 56], moderated MSP outcomes among those living in the lowest quartile of nSES, but not among individuals in less disadvantaged environments. Indeed, although average differences in pain across all time-points between the least and most disadvantaged quartiles of nSES (decrease of 0.6 points on 0-10 NRS or 14% decrease) did not exceed clinical significance (decrease of 1.7 points or 28% decrease [17]), differences according to SNP rs2817038 allele in the most disadvantaged nSES quartile (2.0 points on NRS or 42% decrease) were clinically significant.…”

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“…Specific polymorphisms of genes codifying for serotonin transporters and the catechol-O-methyltransferase enzyme which inactivates catecholamines, neurotransmitters implicated in the pathogenesis of affective disorders, have been associated with FM [5]. It has however been acknowledged that the clinical picture of FM often overlaps with those of the Chronic Fatigue Syndrome and Irritable Bowel Syndrome: response to stress is considered to play a crucial role in the pathogenesis of these disorders [6,7]. But the efficacy of antidepressants in this group of disorders may be related to the analgesic effect of these drugs rather that their antidepressant effect and appears strongest in agents with mixed-receptor or predominantly noradrenergic activity, rather than serotoninergic activity [8]…”