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

BackgroundIn 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.MethodsThe 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.ResultsThe 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.ConclusionsThis 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.

[1]  G. Chrousos Stress, chronic inflammation, and emotional and physical well-being: concurrent effects and chronic sequelae. , 2000, The Journal of allergy and clinical immunology.

[2]  Frank C. Verhulst,et al.  Symptom-specific associations between low cortisol responses and functional somatic symptoms: The TRAILS study , 2012, Psychoneuroendocrinology.

[3]  C. Sommer,et al.  Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. , 2006, Arthritis and rheumatism.

[4]  Daniel S Nagin,et al.  Group-based trajectory modeling in clinical research. , 2010, Annual review of clinical psychology.

[5]  S. Linton,et al.  Early Identification of Patients at Risk of Developing a Persistent Back Problem: The Predictive Validity of The Örebro Musculoskeletal Pain Questionnaire , 2003, The Clinical journal of pain.

[6]  D. Hellhammer,et al.  Stress-Induced Allodynia – Evidence of Increased Pain Sensitivity in Healthy Humans and Patients with Chronic Pain after Experimentally Induced Psychosocial Stress , 2013, PloS one.

[7]  B. Hankin,et al.  Hypocortisolism as a potential marker of allostatic load in children: Associations with family risk and internalizing disorders , 2011, Development and Psychopathology.

[8]  Leslie J Crofford,et al.  Salivary Cortisol and Cold Pain Sensitivity in Female Twins , 2014, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[9]  B. Penninx,et al.  Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study , 2015, Annals of the rheumatic diseases.

[10]  W. Thomson,et al.  Extended Report , 2022 .

[11]  Dieter Wagner,et al.  HPA Axis Reactivity and Lymphocyte Glucocorticoid Sensitivity in Fibromyalgia Syndrome and Chronic Pelvic Pain , 2008, Psychosomatic medicine.

[12]  J. Gurwitz,et al.  Individual and composite study endpoints: separating the wheat from the chaff. , 2014, The American journal of medicine.

[13]  B. Ainsworth,et al.  International physical activity questionnaire: 12-country reliability and validity. , 2003, Medicine and science in sports and exercise.

[14]  P. Luyten,et al.  Central sensitivity syndromes: stress system failure may explain the whole picture. , 2009, Seminars in arthritis and rheumatism.

[15]  F. Seguin,et al.  Effects of stress throughout the lifespan on the brain, behaviour and cognition , 2009 .

[16]  S. Maier,et al.  Central Proinflammatory Cytokines and Pain Enhancement , 2005, Neurosignals.

[17]  P. Morley-Forster,et al.  Long-Term Outcome of the Management of Chronic Neuropathic Pain: A Prospective Observational Study. , 2015, The journal of pain : official journal of the American Pain Society.

[18]  J. Newnham,et al.  Prospective cohort study of factors influencing the relative weights of the placenta and the newborn infant , 1997, BMJ.

[19]  Pedagógia,et al.  Cross Sectional Study , 2019 .

[20]  M. Ernberg,et al.  The influence of menstrual phases on pain modulation in healthy women. , 2012, The journal of pain : official journal of the American Pain Society.

[21]  M. Ingvar,et al.  Suppressed Neuroendocrine Stress Response in Depressed Women on Job-Stress-Related Long-Term Sick Leave: A Stable Marker Potentially Suggestive of Preexisting Vulnerability , 2009, Biological Psychiatry.

[22]  L. Straker,et al.  Low back pain in 17 year olds has substantial impact and represents an important public health disorder: a cross-sectional study , 2012, BMC Public Health.

[23]  B. Beck,et al.  Cross-sectional study , 2011 .

[24]  T. Cole,et al.  Establishing a standard definition for child overweight and obesity worldwide: international survey , 2000, BMJ : British Medical Journal.

[25]  A. Silman,et al.  Moderation of psychosocial risk factors through dysfunction of the hypothalamic-pituitary-adrenal stress axis in the onset of chronic widespread musculoskeletal pain: findings of a population-based prospective cohort study. , 2007, Arthritis and rheumatism.

[26]  C. Kirschbaum,et al.  The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting. , 1993, Neuropsychobiology.

[27]  Ulrike Ehlert,et al.  Trained men show lower cortisol, heart rate and psychological responses to psychosocial stress compared with untrained men , 2007, Psychoneuroendocrinology.

[28]  C. Kirschbaum,et al.  Short-term estradiol treatment enhances pituitary-adrenal axis and sympathetic responses to psychosocial stress in healthy young men. , 1996, The Journal of clinical endocrinology and metabolism.

[29]  P. Hastings,et al.  Multi-Level Risk Factors for Suicidal Ideation Among at-Risk Adolescent Females: The Role of Hypothalamic-Pituitary-Adrenal Axis Responses to Stress , 2015, Journal of abnormal child psychology.

[30]  Rinie Geenen,et al.  Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain: partly masked by depressive and anxiety disorders , 2014, BMC Musculoskeletal Disorders.

[31]  B. Kudielka,et al.  Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. , 1999, Psychosomatic medicine.

[32]  F. Birklein,et al.  Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values , 2006, PAIN.

[33]  J. Rosmalen,et al.  Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms: A longitudinal cohort study in the general population , 2009, Psychoneuroendocrinology.

[34]  C. Kirschbaum,et al.  Human hypothalamus–pituitary–adrenal axis responses to acute psychosocial stress in laboratory settings , 2010, Neuroscience & Biobehavioral Reviews.

[35]  A. Beck,et al.  Assessment of depression: the depression inventory. , 1974, Modern problems of pharmacopsychiatry.

[36]  Stefan Wüst,et al.  Human models in acute and chronic stress: Assessing determinants of individual hypothalamus–pituitary–adrenal axis activity and reactivity , 2010, Stress.

[37]  D. Buchwald,et al.  Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions. , 2003, Best practice & research. Clinical rheumatology.

[38]  Allison L. Jahn,et al.  Circulating cortisol levels after exogenous cortisol administration are higher in women using hormonal contraceptives: data from two preliminary studies , 2014, Stress.

[39]  Nicolas Rohleder,et al.  Predicting the failure of disc surgery by a hypofunctional HPA axis: evidence from a prospective study on patients undergoing disc surgery , 2005, Pain.

[40]  John McBeth,et al.  Epidemiology of chronic musculoskeletal pain. , 2007, Best practice & research. Clinical rheumatology.

[41]  H. D. de Vet,et al.  Hormonal and Reproductive Factors are Associated With Chronic Low Back Pain and Chronic Upper Extremity Pain in Women–The MORGEN Study , 2006, Spine.

[42]  Panos Barlas,et al.  Gender differences in pressure pain threshold in healthy humans , 2003, Pain.

[43]  S. Branje,et al.  Long-term stability of the cortisol awakening response over adolescence , 2013, Psychoneuroendocrinology.

[44]  Hartmut Schächinger,et al.  Increased basal mechanical pain sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism , 2010, PAIN.

[45]  C. Anderson‐Cook,et al.  Group-Based Modeling of Development , 2006 .

[46]  M. Gunnar,et al.  Identifying atypical cortisol patterns in young children: The benefits of group-based trajectory modeling , 2009, Psychoneuroendocrinology.

[47]  B. Kudielka,et al.  Sex differences in HPA axis responses to stress: a review , 2005, Biological Psychology.

[48]  G. Miller,et al.  If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. , 2007, Psychological bulletin.

[49]  S. Dickerson,et al.  Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. , 2004, Psychological bulletin.

[50]  T. Tammelin,et al.  Psychosocial, mechanical, and metabolic factors in adolescents’ musculoskeletal pain in multiple locations: A cross‐sectional study , 2010, European journal of pain.

[51]  Lars Arendt-Nielsen,et al.  Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. , 2009, The journal of pain : official journal of the American Pain Society.

[52]  Andrew Steptoe,et al.  The relationship between cortisol responses to laboratory stress and cortisol profiles in daily life , 2014, Biological Psychology.

[53]  Jami F. Young,et al.  Cortisol reactivity to stress among youth: stability over time and genetic variants for stress sensitivity. , 2015, Journal of abnormal psychology.