The cold pressor test (CPT) involves cold water immersion of either the upper or lower limb(s) and elicits increases in sympathetic nervous activity (SNA), heart rate (HR), and mean arterial pressure (MAP) via stimulation of pain and cutaneous thermoreceptors. Greater pain perception during the CPT is associated with greater increases in SNA and more robust physiological responses. Due to potential differential sensitivity to both painful and thermal stimuli between upper and lower limbs, as well as potential effects of total exposure area, it is unclear whether the choice of limb(s) in CPT protocol design differentially affects systemic and cerebral hemodynamic responses. Our objective was to assess systemic and cerebral hemodynamic and ventilatory responses to different CPT protocols of the hand (CPTH), foot (CPTF), or bilateral feet (CPTBF). We hypothesized CPTBF would elicit greatest physiological responses due to increased exposure area to the cold stimulus. Twenty-eight (14 M, 14 F) healthy young adults [23.4 (SD: 2.4) yr] participated in three 3-min CPT protocols during a single visit. Blood pressure, HR, middle cerebral artery blood velocity (MCAv) and cerebrovascular conductance index, and end-tidal carbon dioxide ([Formula: see text]) were averaged over the final 30 s of each minute of the CPT for each protocol, and perceived pain was recorded at the end of each minute of the CPT. We found significant effects of the time-CPT protocol interaction on systolic blood pressure (P = 0.02), diastolic blood pressure (P < 0.01), MAP (P < 0.01), and HR (P < 0.001). There were no differences between CPT protocols on either MCAv (P = 0.4) or cerebrovascular conductance index (P = 0.1). HR responses peaked in the first minute of the CPT, and changes from baseline were greater in CPTBF [Δ14(16) beats/min] compared with CPTH [Δ5(13) beats/min; P = 0.01] and CPTF [Δ4.04(13.3) beats/min; P = 0.02]. MAP responses peaked in minute 2 of the CPT, and changes from baseline were greater in CPTH [Δ12(8) mmHg) and CPTBF (Δ13(9) mmHg] compared with CPTF [Δ8(7) mmHg; P < 0.01]. Perceived pain was significantly greater in the CPTBF [CPT1 7(2.3), CPT2 6.5(2.3), CPT3 6(3)] condition compared with CPTH [CPT1 6(1.3), CPT2 6(2.3), CPT3 6(2.3)] and CPTF [CPT1 6(3.0), CPT2 6(2.0), CPT3 5.5(3.0)] protocols at all three stages of the CPT (P ≤ 0.01). Our findings suggest choice of limb(s) in CPT protocols may lead to differences in systemic hemodynamic responses, with pain perception potentially influencing these responses. Based on our results, we suggest that choice of limb should be considered in future design of CPT studies, with hand CPT providing the best balance between participant tolerability and robust physiological responses.NEW & NOTEWORTHY Choice of limb(s) in cold pressor test (CPT) studies appears to influence systemic hemodynamics. Hand and bilateral feet induce more robust responses than single-foot CPT, potentially due to increased exposure area and pain perception. Despite no significant cerebrovascular effects, a sustained hyperventilatory response was noted in bilateral feet CPT. Hand CPTs may provide a balance between robust physiological responses and tolerability. These findings underscore the need for careful limb selection in future CPT studies.
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