Repetitive pain experiences modulate feedforward control of hemodynamics and modification by nitrous oxide/oxygen inhalation in humans

Repetitive experiences of certain stresses evoke feedforward cardiovascular responses via central command (CC)--central signals from the higher brain. However, it is unclear whether the anticipatory cardiovascular responses before pain stimulation occur after repetitive pain experiences and how nitrous oxide/oxygen inhalation (N2O), a sedative widely used in dentistry, affects the responses. We tested the hypothesis that the repetitive cold pressor test (CPT) alters the anticipatory cardiovascular responses, which are attenuated by N2O. Beat-to-beat systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), and finger arterial stiffness (β-stiffness) were measured during the 5-min rest, 30-s countdown (CD) before CPT, 2-min CPT, and 3-min recovery (CPT[1st]) in 15 young adults [age, 28 ± 4 years]. The same protocols were repeated randomly with the second CPT (CPT + CC) or placebo test (PLCB + CC). SBP and DBP increased from baseline in CPT[1st] and CPT + CC under room air (RA) and 40 % N2O, while SBP was lower under N2O than under RA in CPT[1st]. HR in CPT[1st] was lower under N2O than under RA. The change (Δ) in HR was smaller during CPT[1st] than during CPT + CC under N2O, and a similar trend was observed under RA. ΔSBP by CD was lower under N2O than under RA in CPT[1st] but not in CPT + CC. HR increased with CD in CPT + CC but not in CPT[1st] under both RA and N2O. β-stiffness increased by CD regardless of the pain experience, while it was lower under N2O. Repetitive pain experiences induce a feedforward HR increase. 40 % N2O decreases vascular stiffness, which may attenuate the anticipatory pressor response only when the feedforward HR increase does not exist. •Repetitive pain stimuli elicit a feedforward HR increase, a risk factor of cardiovascular events.•Nitrous oxide/oxygen inhalation decreased pain sensation and peripheral vascular stiffness.•Nitrous oxide/oxygen inhalation did not decrease HR after repetitive pain experiences.•It attenuated the pressor response via vasodilation only when HR increase does not exist.•Even when nitrous oxide sedation is applied in dentistry, to mitigate pain stress must be needed.