Microchannel Electrode Stimulation of Deep Peroneal Nerve Fascicles Induced Mean Arterial Depressor Response in Hypertensive Rats

Abstract

Hypertension (HTN) affects over 1 billion people in the world, and while most are treated effectively with pharmacological regimens, 10-30% of them do not show a beneficial response. Electrical stimulation of the renal sympathetic, vagus and carotid sinus nerves has shown depressor effects and has been proposed as an alternative treatment for resistant hypertension (R-HTN). However, these nerves are heterogeneous in afferent/efferent composition, and their stimulation often results in unwanted side effects. We evaluated the possibility of eliciting a depressor response from stimulation of single fascicle of the somatic deep peroneal nerve (fDPN). A microchannel electrode array (μCEA) was used to stimulate the fDPN at low frequency, which induced a significant (p ≤ 0.03) transient reduction in mean arterial pressure (MAP) with no significant effects on heart rate. The depressor response was prolonged for several hours by extending the fDPN stimulation to 5 min, which induced significant reduction (17-25%) in MAP for up to 4 h. Immunofluorescence evaluation of the axonal marker, myelin, and active macrophages in the fDPN revealed no indication of nerve damage or overt inflammation in response to the procedure. This study provides evidence supporting the use of μCEA interfacing of small somatic nerve fascicles associated with cardiovascular relevant acupoints to induce significant reductions in MAP and opens the possibility of neuromodulation of small fascicles as an alternative strategy to treat R-HTN with minimal side effects. Further, the μCEA multielectrode array offers an effective tool for neuromodulation of small nerve fascicles, enabling a number of possible future medical bioelectronic applications.

Thin Film Multi-Electrode Softening Cuffs for Selective Neuromodulation

“…Elastomeric polydimethylsiloxane microchannel devices have shown to be effective in recording pelvic nerve activity, but this strategy requires teasing the nerve and placing the small nerve bundles inside a 100 µm microchannel 14 , 43 . We have previously reported a silicon microchannel electrode-array and validated it in acute studies for the fascicular stimulation of the rat deep peroneal nerve 44 , 45 , but the device is stiff and was not designed for chronic implantation. Alternatively, cuff electrodes have been fabricated using polyimide thin film technology (10–25 µm), and demonstrated to be effective in interfacing peripheral nerves without causing compression injury 19 .…”

Miniature electroparticle-cuff for wireless peripheral neuromodulation

“…Electrical stimulation of peripheral nerves is used clinically in several applications including functional electrical stimulation for rehabilitation and foot drop [1,2], vagus nerve stimulation (VNS) for the treatment of epilepsy and tinnitus [3,4], deep peroneal nerve stimulation for hypertension [5], and sacral nerve stimulation for urinary incontinence [6,7]. In addition, PNS neuromodulation is currently investigated for the treatment of autoimmune disorders [8,9] and heart rate modulation [10].…”