Sustained blood pressure reduction associated with percutaneous auricular vagus nerve stimulation in hypertensive chronic pain patients: a retrospective dual-center analysis

Figure 1. Flow diagram illustrating the patient selection process for analysis. A total of 33 patients were assessed for eligibility. Of these, 9 were lost to follow-up. The final analysis included 24 patients who completed all assessments. Patients were categorized into non-hypertensive (n = 13; SBP < 140 mmHg and DBP < 90 mmHg) and hypertensive (n = 11; SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) groups. The hypertensive group was further subdivided into patients without pharmacological hypertension therapy (n = 6) and patients receiving pharmacological hypertension therapy (n = 5).

Figure 2. (a) Schematic representation of the tripolar electrode placement for auricular vagus nerve stimulation (aVNS). (b) Example of aVNS device placement on a patient's ear. (c) Timeline illustrating the intervention and outcome assessment periods, including baseline (BL, week 1), mid treatment (week 4), end of treatment (week 8), and end of follow-up (week 12).

Figure 3. Mean and standard deviation in blood pressure, heart rate, and heart rate variability from baseline (BL, week 1) to mid-treatment (week 4), end of treatment (week 8), and end of follow-up (week 12) in non-hypertensive patients (a–e) and hypertensive patients (f–j). Parameters include systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and root mean square of successive differences in normal RR intervals (RMSSD). Statistically significant pairwise comparisons (p < 0.05) are indicated above the corresponding bars. Y-axis limits are scaled independently for each panel to enhance visualization of within-group longitudinal changes.

Figure 4. Mean and standard deviation in blood pressure, heart rate and heart rate variability markers from baseline (BL, week 1) to mid of treatment (week 4) to end of treatment (week 8) and end of follow up (weeks 12) in hypertensive patients without pharmacological hypertension treatment (a–e) and with pharmacological hypertension treatment (f–j). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and root mean square successive difference in RR intervals (RMSSD). Statistically significant pairwise comparisons (p < 0.05) are indicated above the respective bars.

Figure 5. Relationship between cardiovascular markers at baseline value (week 1) and absolute change at mid-treatment (week 4), end of treatment (week 8), and end of follow-up (week 12) in the entire patient population (a–e) and relationship between absolute changes from baseline as a function of stimulation voltage (f–j). Parameters include systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and root mean square of successive differences in normal RR intervals (RMSSD).

Figure 6. Concordance analysis of hemodynamic vs. analgesic responses across patient subgroups. Scatter plots illustrating the relationship between the change in mean visual analog scale (VAS) score and changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), heart rate (HR), and root mean square of successive differences (RMSSD) in normal RR intervals. Rows represent patient subgroups: (a–e) All Patients, (f–j) Total Hypertensive, (k–o) Hypertensive with Medication, and (p–t) Hypertensive without Medication. Note the strong negative correlation in untreated hypertensive patients (panel p), indicating that greater pain relief is associated with greater SBP reduction. This relationship is absent in medicated patients (panel k) suggesting a decoupling of the analgesic-autonomic response. Green crosses indicate “Dual Responders” (responders for both Pain and BP). Dotted lines represent clinical responder thresholds (VAS: −1.0; SBP: −5.0 mmHg).

Figure 7. Proposed mechanism of action. (a) Schematic representation of the baroreflex pathway, highlighting the role of baroreceptors in the aortic arch, the vagus nerve, and the medulla in regulating sympathetic output to control vascular tone and kidney function. Baroreceptor afferents transmit signals to the nucleus tractus solitarius (NTS) in the medulla, which influences the cardiac control centers, including the vasomotor area, lower motor area, and the cardioinhibitory center, leading to adjustments in blood vessel constriction and renal function via the sympathetic ganglia and the renin-angiotensin system (RAS). (b) Baroreflex sensitivity curve, showing the relationship between sympathetic efferent firing and mean arterial pressure. The solid blue line represents normal baroreflex function, with maximum sensitivity occurring at a specific pressure range. The red dashed line illustrates impaired baroreflex sensitivity in hypertensive conditions. Auricular vagus nerve stimulation (aVNS) is hypothesized to influence baroreflex sensitivity, although this mechanism was not directly assessed in the present study. This schematic is conceptual and intended for illustrative purposes only.…