Valera-Calero, Juan AntonioBuffet-García, JorgeBuffet-García, JorgeKocot-Kępska, MagdalenaKosson, DariuszKołacz, MarcinPlaza-Manzano, Gustavo2026-01-272026-01-272025-11Valera-Calero, J A, Buffet-García, J, Kocot-Kępska, M, Kosson, D, Kołacz, M & Plaza-Manzano, G 2025, 'Relative contribution of real/sham spinal manipulation performance, changes in cortisol levels, and patient expectations and fear behaviors in modulating short-term pain relief in people with neck pain : A secondary analysis of a randomized clinical trial', Musculoskeletal Science and Practice, vol. 80, 103409. https://doi.org/10.1016/j.msksp.2025.1034092468-8630https://hdl.handle.net/10641/7567Publisher Copyright: © 2025 The AuthorsBackground: Spinal manipulation (SM) is a widely practiced, hands-on, non-invasive manual therapy aimed at alleviating musculoskeletal pain and improving functional capacity. Although the clinical effects of this intervention are well known, most reviews conclude that the underlying mechanisms needs further investigation. Therefore, the aim of this study was to analyze the individual contribution of SM execution, expectations, fear behaviors and neuroendocrine changes on short-term pain intensity variance following the interventions. Design: Experimental study. Methods: A secondary analysis from a previous randomized clinical trial was conducted. Sixty-two patients were randomized for two factors: the intervention assigned (cervical manipulation and sham manipulation) and the induced expectations (positive, neutral and negative) during treatment. A linear regression analysis was conducted to calculate the individual contribution of the SM execution (sham/real), expectations conditioning (positive/negative/neutral), fear behaviors (fear/no fear) and neuroendocrine changes (salivary cortisol) on the variance of immediate pain intensity changes (pre-post intervention difference) following the single intervention. Results: Changes in salivary cortisol (β = −0.027, p = 0.838) and fear (β = −0.192, p = 0.135) were not significant explanatory variables of pain intensity response (p > 0.05). However, verbally-induced expectations (β = 0.722, p < 0.001) and the manipulation execution (β = 0.207, p = 0.019) showed a significant positive association with pain intensity response, suggesting that positive expectations had a meaningful impact on reducing pain intensity and a real intervention may involve specific hypoalgesic responses. Conclusion: Clinicians should consider that patients' expectations may influence clinical outcomes. Verbally expressing positive or neutral expectations may improve pain-related outcomes, whereas conveying negative expectations could diminish the treatment's effectiveness.590297enghttp://creativecommons.org/licenses/by-nc-nd/4.0/Expectations conditioningManual therapyNeuroendocrine systemSpinal manipulationPhysical Therapy, Sports Therapy and RehabilitationYesyesjournal articleopen access10.1016/j.msksp.2025.103409https://www.scopus.com/pages/publications/105015510173https://www.scopus.com/pages/publications/105015510173#tab=citedBy