Further research on subjects with spinal MSK conditions with larger sample sizes are needed to obtain more insights about the biological effects of spinal manipulative therapy. Conclusions: Although spinal manipulations seem to trigger the activation of the neuroimmunoendocrine system, the evidence supporting a biological account for the application of HVLAT in clinical practice is mixed and conflicting. Four studies examined the effects of SMT on the immune system and all of them were conducted on healthy individuals. Nine studies investigated the effects of SMT on cortisol levels and five of them were conducted on symptomatic populations. Results: The electronic search retrieved 13 relevant articles and two themes of discussion were developed. Studies were included if they evaluated the effects of HVLAT on participants’ biomarkers. An electronic search on MEDLINE, ProQUEST, and Google Scholar followed by a hand and “snowballing” search were conducted to find relevant articles. Materials and Methods: Narrative critical review. The aim of this paper is to provide an overview of the available evidence supporting the biological plausibility of high-velocity, low-amplitude thrust (HVLAT) on the immune-endocrine system. It has been suggested that other phenomena like neurophysiological responses and the activation of the immune-endocrine system may explain variability in pain inhibition after the administration of spinal manipulative therapy (SMT). While previous theoretical principles focused predominantly on biomechanical accounts, recent models propose that the observed pain modulatory effects of this form of manual therapy may be the result of more complex mechanisms. Background and Objectives: Spinal manipulations are interventions widely used by different healthcare professionals for the management of musculoskeletal (MSK) disorders.
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