Abstract
High blood pressure (BP) is a highly controllable risk factor for cardiovascular diseases; however, awareness of this condition and the rates of controlled hypertension are low. Experimental animal studies have shown that stimulation of the median nerve or PC6 acupoint over the wrist has effects on cardiovascular activities, including reductions in systolic and diastolic BPs. A proof-of-concept study was conducted in humans to investigate whether stimulation of median nerve near PC6 acupoint decreased high BP, identify the optimal stimulation parameters for the BP-lowering effects of median nerve stimulation, and determine the specific peripheral nerves or types of afferent fibers mediating the BP-lowering effects. Median nerve stimulation was carried out bilaterally or unilaterally with different stimulation parameters, and the BP and heart rate were monitored. The afferent mechanisms underlying the effects of median nerve stimulation on hypertension were investigated via microneurography, A-fiber blocking experiments, and localized chemical or electrical stimulation. Bilateral median nerve stimulation at either low or high frequencies produced profound but transient reductions in systolic BP, which were elicited when median nerve stimulation was unilaterally applied at interelectrode distances of 2 and 4 cm. Systolic BP was also reduced by electrical stimulation of the thumb on the palm side. Although microneurographic recordings revealed the excitation of both A- and C-fibers following median nerve stimulation, the median nerve-mediated reductions in BP were not affected by A-fiber blockade, and they were mimicked by the activation of C-fibers with capsaicin. The present results indicate that activation of C-fibers in the median nerve generates BP-lowering effects in humans. Based on our clinical study, an optimized median nerve stimulator was built and combined with a wrist BP monitor for simultaneous BP measurements and median nerve stimulation.
Highlights
Hypertension is one of the most common and most serious diseases and is estimated to impact more than 1 billion people worldwide[1]
While the control group (Con; no transcutaneous median nerve stimulation (TMNS)) showed high systolic blood pressure (BP), the administration of TMNS at frequencies of 3, 10 and 300 Hz significantly reduced the systolic BP compared to the basal systolic BP, with the greatest effect observed at 15 min after the initiation of stimulation
The application of TMNS at either 10 or 300 Hz exerted a profound but transient effect on reducing the systolic BP compared to the effects of other treatments (Con vs. 3 or 30 Hz; two-way repeated measures analysis of variance (ANOVA): group factor, F = 35.235, p < 0.001; time factor, F = 18.021, p < 0.001; Fig. 1B)
Summary
Hypertension is one of the most common and most serious diseases and is estimated to impact more than 1 billion people worldwide[1]. While antihypertensive drugs are commonly prescribed for hypertension, there has been interest in device-based therapies designed to nonpharmacologically modulate cardiovascular functions. Therapeutic interventions, including deep brain stimulation (DBS) of the periaqueductal gray matter (PAG), vagus nerve stimulation, baroreflex activation therapy, renal denervation or carotid body ablation, are known to lower or raise BP and/or heart rate (HR)[6]. Those methods require invasive procedures or are not amenable to long-term www.nature.com/scientificreports/. Based on the results from the aforementioned proof-of-concept study, the present study aimed to develop a noninvasive, wrist-worn neuromodulation device for lowering BP
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