Low frequency conduction block: a promising new technique to advance bioelectronic medicines

Nerve conduction block is an appealing way to selective target the nervous system for treating pathological conditions. Several modalities were described in the past, with the kilohertz frequency stimulation generating an enormous interest and tested successfully in clinical settings. Some shortcomings associated with different modalities of nerve blocking can limit its clinical use, as the “onset response”, the high demand of energy supply, among others. A recent study by Muzquiz and colleagues describes the efficacy and reversibility of low frequency alternating currents in blocking the cervical vagus in the pig, in the absence of an onset effect and apparent lack of neuronal damage.

A Reversible Low Frequency Alternating Current Nerve Conduction Block Applied to Mammalian Autonomic Nerves

Electrical stimulation can be used to modulate activity within the nervous system in one of two modes: (1) Activation, where activity is added to the neural signalling pathways, or (2) Block, where activity in the nerve is reduced or eliminated. In principle, electrical nerve conduction block has many attractive properties compared to pharmaceutical or surgical interventions. These include reversibility, localization, and tunability for nerve caliber and type. However, methods to effect electrical nerve block are relatively new. Some methods can have associated drawbacks, such as the need for large currents, the production of irreversible chemical byproducts, and onset responses. These can lead to irreversible nerve damage or undesirable neural responses. In the present study we describe a novel low frequency alternating current blocking waveform (LFACb) and measure its efficacy to reversibly block the bradycardic effect elicited by vagal stimulation in anaesthetised rat model. The waveform is a sinusoidal, zero mean(charge balanced), current waveform presented at 1 Hz to bipolar electrodes. Standard pulse stimulation was delivered through Pt-Black coated PtIr bipolar hook electrodes to evoke bradycardia. The conditioning LFAC waveform was presented either through a set of CorTec® bipolar cuff electrodes with Amplicoat® coated Pt contacts, or a second set of Pt Black coated PtIr hook electrodes. The conditioning electrodes were placed caudal to the pulse stimulation hook electrodes. Block of bradycardic effect was assessed by quantifying changes in heart rate during the stimulation stages of LFAC alone, LFAC-and-vagal, and vagal alone. The LFAC achieved 86.2±11.1% and 84.3±4.6% block using hook (N = 7) and cuff (N = 5) electrodes, respectively, at current levels less than 110 µAp (current to peak). The potential across the LFAC delivering electrodes were continuously monitored to verify that the blocking effect was immediately reversed upon discontinuing the LFAC. Thus, LFACb produced a high degree of nerve block at current levels comparable to pulse stimulation amplitudes to activate nerves, resulting in a measurable functional change of a biomarker in the mammalian nervous system.

Conduction block as an electrophysiological phenomenon: a review of the literature

Evaluation and interpretation of electrophysiological phenomena often plays an important role in the diagnosis of neuromuscular diseases. Motor nerve conduction block is a reduction of either amplitude or area of the compound motor action potential elicited by proximal to distal motor nerve stimulation. Today, the value of conduction block in the diagnosis of demyelinating and axonal neuropathies, as well as the diagnostic criteria for these disorders, are still under discussion.Objective of the review of the literature is to highlight the value of conduction block as an electrophysiological phenomenon in the light of clinical manifestations. There is no consensus in the literature which motor response parameters should be used as partial conduction block criteria. The diversity of pathogenic forms in which conduction block can be registered does not allow to consider the phenomenon as a sign of only demyelinating lesions, and the term conduction block should be considered as a pure electrophysiological phenomenon. Different pathophysiological mechanisms of conduction block formation should be studied separately within each nosology. Conduction block detection does not allow to specify a particular diagnosis, however, in conjunction with clinical and anamnestic data, it may be the main argument in the diagnosis of a number of peripheral nerves diseases.