Attenuation of hypertension by C-fiber stimulation of the human median nerve and the concept-based novel device

Figures

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  Figure 1. Effects of TMNS applied at different frequencies on hypertension. (A) Experimental scheme. Transcutaneous median nerve stimulation (TMNS) and measurements of blood pressure (BP) and heart rate (HR). (B–D) Changes in systolic BP (B), diastolic BP (C) and HR (D) following the application of bilateral TMNS at frequencies of 3, 10, 30 or 300 Hz. The application of TMNS at 10 or 300 Hz transiently reversed the changes in systolic BP compared to the control (Con), although neither diastolic BP nor HR were altered. *p < 0.05 vs. the values recorded before TMNS (Time 0); and #p < 0.05 vs. the Con group.

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  Figure 2. Comparison of the effects of unilateral or bilateral TMNS on hypertension. (A–C) Changes in systolic blood pressure (BP) (A), diastolic BP (B) and HR (C) following the application of unilateral or bilateral TMNS. The data for bilateral TMNS shown in (A–C) are duplicated from the 10-Hz group shown in Fig. 1 according to recommendations of the IRB. The application of unilateral (left hand) or bilateral TMNS at a frequency of 10 Hz significantly decreased systolic BP compared to the values recorded before TMNS. A significant difference was not observed between the two groups (unilateral vs. bilateral). *p < 0.05 vs. the values obtained before TMNS (Time 0).

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  Figure 3. Effects of the interelectrode distance for TMNS on hypertension. (A) Experimental scheme. Placement of electrodes (black, anode; red, cathode) and measurements of blood pressure (BP) and heart rate (HR). (B–D) Changes in systolic BP (B), diastolic BP (C) and HR (D) following the application of unilateral TMNS (10 Hz, left hand) at distances of 2, 4 or 6 cm between the two electrodes. *p < 0.05 vs. the values obtained before TMNS (Time 0); #p < 0.05 vs. the 6 cm-group.

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  Figure 4. Effects of electrical stimulation of the skin over the median or ulnar nerve on hypertension. (A) Experimental scheme. Location of electrodes for stimulation of the median nerve (Median site #1 and #2) or ulnar nerve (Ulnar site) sites and measurement of BP and HR. (B–D) Changes in systolic BP (B), diastolic BP (C) and HR (D) following electrical stimulation (10 Hz) of the skin innervating the median or ulnar nerve on the left hand. Decreases in systolic BP were more profound following the stimulation of the median nerve sites (Median site #1 & #2) than the stimulation of the ulnar nerve site (Ulnar site; A). Electrical stimulation of the palm side of the thumb (Median site #2) also tended to decrease diastolic BP and HR. *p < 0.05 vs. the value obtained before TMNS (Time 0). #p < 0.05 vs. the Ulnar site.

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  Figure 5. Microneurographic recordings of the median nerve during TMNS. (A) Experimental scheme for median nerve microneurography and TMNS (10 Hz, left hand). (B) Representative trace of fiber discharges during TMNS. Asterisks indicate electrical artifacts from 10-Hz TMNS. (C–E) A representative histogram (C) and mean values (E, n = 5 persons) of A-fiber discharges before and after TMNS. (D and F) Representative histogram (D and F) mean values (F, n = 5 persons) of C-fiber discharges before and after TMNS. *p < 0.05 vs. mean values obtained before TMNS (Times 1–10).

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  Figure 6. Effects of a median nerve A-fiber block (AFB) on TMNS-induced antihypertensive effects. (A–C) AFB of the median nerve induced by compression in 6 subjects. Compression over the median nerve was performed with a 1.5-kg weight (A), and mechanical (B) and thermal sensitivities (C) were evaluated using von Frey filaments and warm water (57 °C), respectively. Mechanical thresholds were increased slowly, reaching a log value of 3.61 at 80 min after compression, whereas the thermal sensitivity in response to the 57 °C water was not changed after compression for up to 120 min. (D–F) Effect of the median nerve AFB on TMNS-induced antihypertensive effects on hypertensive subjects (n = 5). Changes in systolic BP (D), diastolic BP (E) and HR (F) following the application of TMNS (unilateral, 10 Hz) to the left hand subjected to 80 min of compression to establish a median nerve AFB. *p < 0.05 vs. the values obtained before TMNS.

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  Figure 7. Effect of a topical capsaicin treatment to the skin over the median nerve on hypertension. (A) Experimental scheme. (B–D) Changes in systolic BP (B), diastolic BP (C) and HR (D) following the topical capsaicin treatment over the median nerve of the left hand. *p < 0.05 vs. the values obtained before the capsaicin treatment.

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  Figure 8. Prototype wrist-worn BP neuromodulation device. (A) Schematic of a TMNS-coupled BP monitor. (B) Prototype device constructed by attaching the newly developed TMNS unit to a commercial wrist BP monitor. TMNS, transcutaneous median nerve stimulation; and BP, blood pressure.