Orexin-A and Periosteal Pressure Sensitivity during acute mental and physical stress: a randomized cross-over study

Objective physiological markers reflecting central autonomic regulation remain limited. The orexin (hypocretin) system, localized in the lateral hypothalamus, integrates arousal, metabolic state, cardiovascular control, homeostatic control, and stress responsiveness. Periosteal Pressure Sensitivity (PPS) at the sternum has been proposed as a peripheral marker for central sympathetic activation. The present study examined for the first time the association between PPS and salivary orexin-A during experimentally induced mental and physical stress and subsequent recovery.

In this randomized cross-over study, 20 healthy female participants (20-28 years) completed two experimental procedures in randomized order: Maastricht Acute Stress Test (MAST) and Moderate-Intensity Interval Training (MIIT). PPS, systolic blood pressure, heart rate, Pressure-Rate Product (i.e., systolic blood pressure × heart rate) and salivary orexin-A were measured at baseline, immediately post-procedure, as well as 15 and 30 mins into recovery. MIIT results were analyzed both for the full sample (n = 20) and for the participants who fulfilled the protocol-defined cardiovascular response criterion (n = 12).

MAST did not induce significant baseline-to-post-stress changes in PRP, PPS, or salivary orexin-A, although PRP decreased significantly during early recovery from S2 to S3 (p = 0.045). A significant negative correlation was observed between ΔPPS and ΔPRP from S1 to S2 (r = -0.47, p = 0.035). MIIT induced a marked increase in PRP followed by a decrease during recovery. Changes in PPS and salivary orexin-A were not significantly correlated in the full MIIT sample. In the separate MIIT sub-analysis, a positive correlation was observed during the 30-min recovery period (r = 0.76, p = 0.029, and n = 8).

MIIT produced a clear cardiovascular response, whereas MAST did not produce the expected immediate cardiovascular stress response. The MIIT sub-analysis supports a possible association between changes in salivary orexin-A and PPS during recovery but does not establish a causal or central orexin-mediated mechanism. Replication in a larger population using technically successful and standardized MIIT and MAST procedures is required.