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      A low cortisol response to stress is associated with musculoskeletal pain combined with increased pain sensitivity in young adults: a longitudinal cohort study

      Arthritis Research & Therapy
      BioMed Central
      musculoskeletal, hypersensitivity, quantitative sensory testing, cortisol, trajectory modeling

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          Abstract

          Background In this study, we investigated whether an abnormal hypothalamic-pituitary-adrenal (HPA) axis response to psychosocial stress at 18 years of age is associated with musculoskeletal (MS) pain alone and MS pain combined with increased pain sensitivity at 22 years of age. Methods The study sample included 805 participants from the Western Australian Pregnancy Cohort (Raine) Study who participated in the Trier Social Stress Test (TSST) at age 18 years. Number of pain sites, pain duration, pain intensity and pain frequency were assessed at age 22 to measure severity of MS pain. Cold and pressure pain thresholds were determined at age 22. Group-based trajectory modeling was applied to establish cortisol response patterns based on the TSST. Logistic regression was used to study the association of TSST patterns with MS pain alone and MS pain combined with increased cold or pressure pain sensitivity, adjusted for relevant confounding factors. All analyses were stratified by sex. Results The mean (standard deviation) age during the TSST was 18.3 (0.3) years, and during MS pain assessment it was 22.2 (0.6). Forty-five percent of the participants were female. Three cortisol response patterns were identified, with cluster 1 (34 % of females, 21 % of males) reflecting hyporesponse, cluster 2 (47 %, 54 %) reflecting intermediate response and cluster 3 (18 %, 24 %) reflecting hyperresponse of the HPA axis. MS pain was reported by 42 % of females and 33 % of males at age 22 years. Compared with females in cluster 2, females in cluster 1 had an increased likelihood of having any MS pain (odds ratio 2.3, 95 % confidence interval 1.0–5.0) and more severe MS pain (2.8, 1.1–6.8) if their cold pain threshold was above the median. In addition, females in cluster 1 had an increased likelihood (3.5, 1.3–9.7) of having more severe MS pain if their pressure pain threshold was below the median. No statistically significant associations were observed in males. Conclusions This study suggests that a hyporesponsive HPA axis at age 18 years is associated with MS pain at 22 years in young females with increased pain sensitivity.

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          Most cited references36

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          Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera.

          Quantification of the human painful sensory experience is an essential step in the translation of knowledge from animal nociception to human pain. Translational models for assessment of pain are very important, as such models can be used in: 1) basic mechanistic studies in healthy volunteers; 2) clinical studies for diagnostic and monitoring purposes; 3) pharmacological studies to evaluate analgesic efficacy of new and existing compounds. Quantitative pain assessment, or quantitative sensory testing (QST), provides psychophysical methods that systematically document alterations and reorganization in nervous system function and, in particular, the nociceptive system. QST is defined as the determination of thresholds or stimulus response curves for sensory processing under normal and pathophysiological conditions. The modern concept of advanced QST for experimental pain assessment is a multimodality, multitissue approach where different pain modalities (thermal, mechanical, electrical, and chemical) are applied to different tissues (skin, muscles, and viscera) and the responses are assessed by psychophysical methods (thresholds and stimulus-response functions). Many new and advanced technologies have been developed to help relieve evoked, standardized, and painful reactions. Assessing pain has become a question of solving a multi-input, multi-output problem, with the solution providing the possibility of teasing out which pain pathways and mechanisms are involved, impaired, or affected. Many methodologies have been developed for quantitative assessment of pain perception and involved mechanisms. This paper describes the background for the different methods, the use in basic pain experiments on healthy volunteers, how they can be applied in drug profiling, and the applications in clinical practice.
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            Human hypothalamus-pituitary-adrenal axis responses to acute psychosocial stress in laboratory settings.

            Cumulative acute psychosocial stress is thought to promote the development of a range of disorders which suggests that biomarkers for the physiological response may become valuable tools for biomedical research and development. The search for these biomarkers has been aided by the development of a standardised protocol for inducing psychosocial stress that combines social-evaluative threat and uncontrollability, i.e., the Trier Social Stress Test (TSST). Among other biological markers of acute stress, this test induces significant changes of the hypothalamus-pituitary-adrenal axis (HPAA), which is thought to play a pivotal role in the generation of stress-associated pathologies. The HPAA responses show differences between patients and healthy subjects as well as between pathologies. Moreover, gender, age, personality traits, social environment, and genotype can also shape the individual's acute stress response triggered by the TSST. Characterization of the roles and interactions of these factors in generating a dysregulation of the neuroendocrine responses to acute psychosocial stress await longitudinal studies.
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              Trained men show lower cortisol, heart rate and psychological responses to psychosocial stress compared with untrained men.

              Physical activity has proven benefits for physical and psychological well-being and is associated with reduced responsiveness to physical stress. However, it is not clear to what extent physical activity also modulates the responsiveness to psychosocial stress. The purpose of this study was to evaluate whether the reduced responsiveness to physical stressors that has been observed in trained men can be generalized to the modulation of physiological and psychological responses to a psychosocial stressor. Twenty-two trained men (elite sportsmen) and 22 healthy untrained men were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). Adrenocortical (salivary free cortisol levels), autonomic (heart rate), and psychological responses (mood, calmness, anxiety) were repeatedly measured before and after stress exposure. In response to the stressor, cortisol levels and heart rate were significantly increased in both groups, without any baseline differences between groups. However, trained men exhibited significantly lower cortisol and heart rate responses to the stressor compared with untrained men. In addition, trained men showed significantly higher calmness and better mood, and a trend toward lower state anxiety during the stress protocol. On the whole, elite sportsmen showed reduced reactivity to the psychosocial stressor, characterized by lower adrenocortical, autonomic, and psychological stress responses. These results suggest that physical activity may provide a protective effect against stress-related disorders.
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                Author and article information

                Journal
                4674918
                10.1186/s13075-015-0875-z
                http://creativecommons.org/licenses/by/4.0/

                Orthopedics
                musculoskeletal,hypersensitivity,quantitative sensory testing,cortisol,trajectory modeling

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