353: Stress Biomarker Trajectories Linked to Pain Vulnerability in Randomised Chiropractic Trials

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, Non-pharmacological treatments, Treatment/management

Background and Aims: Psychological and physiological stress contribute to pain vulnerability and chronification via shared neuroendocrine and autonomic mechanisms. Dysregulation of the hypothalamic–pituitary–adrenal axis and heightened stress responses are associated with increased pain sensitivity and poorer pain outcomes. Understanding how clinical interventions influence stress-related biomarkers in subclinical populations may provide insights into early pain risk and prevention.
The objective of the study was to characterise trajectories and predictors of psychological and physiological stress outcomes over 12 weeks in two randomised controlled trials (RCTs) of chiropractic care in adults and children with subclinical spinal pain, and to identify baseline and clinical factors influencing trajectories.

Methods: We performed secondary analyses of two parallel group RCTs in which adults and children were randomised to chiropractic care or control over 12 weeks. Outcomes included psychological stress (DASS-21 in adults) and physiological stress biomarkers (salivary, blood, and hair cortisol). Weighted spinal dysfunction scores were derived from clinical records across treatment sessions. Linear mixed effects models examined longitudinal associations between baseline stress, spinal dysfunction, randomised group, and follow-up stress outcomes. Predictive models (Random Forest, Gradient Boosting, Support Vector Regression) were trained using baseline and clinical variables; performance was evaluated with cross-validated R² and RMSE.

Results: In adults, baseline physiological and psychological stress measures were the strongest predictors of 12-week stress outcomes, with blood cortisol increasing by approximately 19% post-intervention and DASS-21 scores decreasing by about 35% from baseline; linear mixed-effects and machine-learning models explained a moderate proportion of variance in outcomes (R² ≈ 0.64–0.78 for blood cortisol and R² ≈ 0.43–0.47 for DASS-21). Self-reported psychological stress decreased across both groups, while cortisol levels tended to increase, indicating divergent patterns of subjective and physiological stress adaptation. Analyses in the paediatric RCT were underpowered and yielded inconclusive findings.

Conclusions: In the subclinical population, baseline physiological and psychological stress measures emerged as the strongest predictors of 12-week stress outcomes, while associations with spinal dysfunction scores and chiropractic care were modest. Psychological stress improved over time, whereas physiological stress markers increased, indicating divergence between subjective and biological stress responses. This pattern may reflect altered HPA-axis regulation or increased physiological responsiveness, representing adaptive neuroendocrine engagement in response to care and tissue reactivation. Such divergence highlights the complexity of stress regulation in subclinical states and may be relevant to understanding mechanisms associated with pain vulnerability and future pain risk.

References: Ménard C, Pfau ML, Hodes GE, Russo SJ. Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology. 2017;42(1):155–177.
​Bhattacharya A, Dhabhar FS. Neuroendocrine and cellular mechanisms in stress resilience. Stress Health. 2024;40(2):123–145.
​
Sic A, et al. Chronic stress and headaches: the role of the HPA axis and glucocorticoids in pain chronification. Pain Rep. 2025;10(1):e1205.
​
Vachon-Presseau E, et al. Cortisol overresponsiveness as a marker of vulnerability to chronic pain: evidence from human and animal studies. Pain. 2013;154 Suppl 1:S47–S55.

Lovibond PF, Lovibond SH. The structure of negative emotional states: Comparison of the Depression Anxiety Stress Scales (DASS) with the Beck inventories. Behav Res Ther. 1995;33(3):335–343.
​
Nilges P, Essau C. Depression, anxiety and stress scales: DASS – a screening procedure not only for pain patients. Pain. 2015;156(5):783–784.
​
Yohannes S, et al. Psychometric properties of the Depression, Anxiety, and Stress Scale-21 (DASS-21) in clinical and non-clinical populations. BMC Psychiatry. 2025;25:312.

Deyo RA, Weinstein JN. Low back pain. N Engl J Med. 2001;344(5):363–370.
​
Von Korff M, Dunn KM. Chronic pain reconsidered. Pain. 2008;138(2):267–276.
​
Kongsted A, et al. Distinguishing low‑risk from high‑risk back pain in primary care: implications for early intervention. BMC Musculoskelet Disord. 2014;15:221.

Vachon-Presseau E, et al. Cortisol reactivity and the development of chronic pain: psychoneuroendocrine mechanisms. Psychoneuroendocrinology. 2013;38(12):2758–2769.
​
al’Absi M, Petersen KL. Blood pressure but not cortisol mediates stress effects on subsequent pain perception in healthy men and women. Pain. 2003;106(3):285–295.
​
Turner-Cobb JM. Psychological and stress hormone predictors of pain outcomes: a review. J Psychosom Res. 2013;74(6):494–501.

McEwen BS. Stress, adaptation, and disease: allostasis and allostatic load. Ann N Y Acad Sci. 1998;840:33–44.

de Kloet ER, Joëls M, Holsboer F. Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005;6(6):463–475.
​
Bhattacharya A, Dhabhar FS. Neuroendocrine mechanisms in stress resilience. Stress Health. 2024;40(2):123–145.
​
Ogutu JO, Piepho HP, Schulz-Streeck T. A comparison of random forests, boosting and support vector machines for genomic selection. BMC Proc. 2011;5(Suppl 3):S11.
​
Naik A, et al. SGO‑enhanced random forest and extreme gradient boosting for heart disease prediction. Sci Rep. 2025;15:12580.

Wiech K. Deconstructing the sensation of pain: the influence of cognitive processes on pain perception. Science. 2016;354(6312):584–587.
​
Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55(3):377–391.

Presenting Author: Imran Amjad
Submitting Author: IMRAN AMJAD

Senior Author: Imran Khan Niazi

IASP 2026 Global Year theme of Neuropathic Pain: No

• Imran Khan Niazi: PhD - Centre for Chiropractic Research, New Zealand College of Chiropractic, Auckland 1060, New Zealand
• Seyed Hosseini: PhD - Whitecliffe College, New Zealand.
• Shahbaz Pervez: PhD - Whitecliffe College, New Zealand.
• Kelly Holt: PhD - Centre for Chiropractic Research, New Zealand College of Chiropractic, Auckland 1060, New Zealand
• Mannat Ahuja: MS - Auckland University of Technology, Auckland, New Zealand
• Heidi Haavik: PhD - Centre for Chiropractic Research, New Zealand College of Chiropractic, Auckland 1060, New Zealand