Physiological responses to manual therapy in healthy humans: an experimental study on the relationship between applied pressure, manual technique, and autonomic, hormonal, and vascular responses. A randomized clinical trial.

This study protocol describes a randomized crossover experimental study designed to characterize the acute physiological responses induced by manual therapy protocols involving different pressure intensities in healthy adults. Manual therapy techniques are widely used in physiotherapy and clinical practice, including in vulnerable populations such as people living with or beyond cancer. However, the physiological safety profile of different manual pressure intensities remains insufficiently characterized. In particular, there is limited evidence on whether light, moderate, and lymphatic manual therapy protocols induce differentiated autonomic, hormonal, immune, sensory, and vascular responses under controlled experimental conditions. The study will include healthy adults aged 18 to 65 years. Each participant will receive three standardized manual therapy protocols in separate experimental sessions and in randomized order: manual lymphatic drainage, oncology massage, and decontracting massage. The study uses a within-subject crossover design, allowing each participant to act as their own control. The main outcomes include autonomic responses, assessed through heart rate, heart rate variability, skin temperature, galvanic skin response, and blood pressure; sensory responses, assessed through mechanical pain threshold; hormonal and immune responses, assessed through capillary blood markers including cortisol, vascular endothelial growth factor, interleukin-6, and leukocyte subpopulations; and vascular responses, assessed by B-mode and Doppler ultrasound of the left common carotid artery. Body composition will also be assessed using dual-energy X-ray absorptiometry, and subjective perception of massage intensity and effects will be recorded after each intervention. The protocol aims to provide a controlled physiological model for understanding the immediate effects and safety profile of graded manual pressure. Although the study is conducted in healthy adults, its findings may provide a translational basis for future clinical research in oncology and other vulnerable populations, contributing to the standardization, personalization, and safer clinical use of manual therapy techniques. Trial registration: ClinicalTrials.gov, NCT07393815.