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

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.

Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study

“…The distinct findings might also be explained by measurement differences, for example, in the assessment of pain, depression or cortisol 37. Several cross-sectional studies showed biological alterations in chronic pain3 8 also in the Netherlands Study of Depression and Anxiety sample 9 12. Our current finding of no associations with chronic pain onset might therefore suggest that these biological changes are consequences rather than risk factors for developing this condition.…”

“…Moreover, interaction effects were tested with life events and with psychopathology that are known to influence biological stress systems functioning. Thus, if dysregulated biological stress systems would play an important role in the onset of chronic pain, our study should have been able to show this, especially since our cross-sectional findings did indicate biological alterations in chronic pain 9 12…”

“…No moderating effect of depression and/or anxiety was found in the association between any biological variable with the onset of chronic pain (all p-interaction>0.10). We additionally checked whether associations existed for the first cortisol value at awakening and the diurnal cortisol slope (calculated by subtracting the value at 23:00 from the cortisol value at awakening and dividing it by the number of hours in-between the two samples), as these were cross-sectionally associated with chronic pain before,9 but no such associations were found either. Analyses considering only subjects with chronic pain for ≥90 days (n=215) showed similar HR for all biological variables (p>0.05) but evening cortisol (fully adjusted HR (95% CI) 1.30(1.09 to 1.55); p=0.003).…”

“…A potential moderating effect of life events in the association between biological stress systems and chronic pain onset was examined by adding an interaction term (biological variable×number of life events) to each analysis. Since the HPA axis could be hypoactive or hyperactive,9 non-linear associations between cortisol measures and chronic pain onset were examined by entering quadratic terms of cortisol measures to the model also including the linear terms. Since our previous study found hypocortisolemia particularly among chronic pain subjects without depressive or anxiety disorders,9 we tested whether lifetime depression and/or anxiety moderated the association between biological stress systems and chronic pain onset by including biological variable×psychopathology (yes/no) interaction terms in the analyses.…”

Ağrının kronikleşmesine neden olan faktörler, patofizyoloji temelli tedaviler

“…Otonom sinir sisteminde parasempatik sistem aktivitesinin azalması, sempatik sistemin aşırı aktivitesi ile strese verilen yanıtın değişmesi, sensitizasyonu indükleyebilmektedir. [34] PATOFİZYOLOJİ TEMELLİ TEDAVİLER Ağrıda nosiseptif ve inflamatuvar ağrı mekanizmaları hakim ise basit analjezikler (parasetamol), nonsteroidal ağrı kesiciler ya da daha şiddetli ağrılarda güçlü analjezikler olarak opioidler kullanılmaktadır. Kronik ağrı, tedavisi güç bir hastalıktır.…”