Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Damage-free peripheral nerve stimulation by 12-ns pulsed electric field.
Casciola M
,
Xiao S
,
Pakhomov AG
.
???displayArticle.abstract???
Modern technologies enable deeptissue focusing of nanosecond pulsed electric field (nsPEF) for non-invasive nerve and muscle stimulation. However, it is not known if PEF orders of magnitude shorter than the activation time of voltage-gated sodium channels (VGSC) would evoke action potentials (APs). One plausible scenario requires the loss of membrane integrity (electroporation) and resulting depolarization as an intermediate step. We report, for the first time, that the excitation of a peripheral nerve can be accomplished by 12-ns PEF without electroporation. 12-ns stimuli at 4.1-11 kV (3.3-8.8 kV/cm) evoked APs similarly to conventional stimuli (100-250 μs, 1-5 V, 103-515 V/m), except for having higher selectivity for the faster nerve fibers. Nerves sustained repeated tetanic stimulations (50 Hz or 100 Hz for 1 min) alternately by 12-ns PEF and by conventional pulses. Such tetani caused a modest AP decrease, to a similar extent for both types of stimuli. Nerve refractory properties were not affected. The lack of cumulative damages even from tens of thousands of 12-ns stimuli and the similarities with the conventional stimulation prove VGSC activation by nsPEF without nerve membrane damage.
Figure 1. Block diagram of the setup for 12-ns PEF stimulation. Isolated nerve is placed in the conduction chamber which permits switching between 12-ns PEF (red arrows) and conventional stimulation (blue arrows). See Fig. 2 and text for more details.
Figure 2. Conduction chamber design and electric stimulation of the nerve. (a) Schematic of the conduction chamber. The nerve (not shown) is placed atop the metal pins and the open central conductor of the coaxial line. (b) A photo of the chamber, with the approximate position of the nerve shown by a dashed line. (c) Scattering parameters of the conduction chamber. Modules of the reflection and transmission coefficients (|S11| and |S21|, respectively) over frequency as obtained from HFSS simulations (solid lines) and from VNA measurements (dashed lines). (d) The shape of the 12-ns pulse (top), with the width of 12–14 ns at 50% height, and the spectrum of an ideal pulse used for simulations (10 ns plateau, 1 ns rise and fall times).
Figure 3. Electric field simulation results for conventional (a) and nsPEF (b) stimulation of the isolated nerve. Upper panels show the electric field distribution in a plane crossing the nerve perpendicular to stimulating electrodes. Note different values of the voltage input and different units for the electric field strength (1 V and V/m in a; 1 kV and kV/cm in b). Lower panels show the electric field values in the same plane, at four indicated depths into the nerve. For both conventional and nsPEF stimuli, action potentials in the nerve will be elicited at the cathode (pin 3). The electric field values reported elsewhere in this paper are the maximum values found over the cathode at the depth of 0.1875 mm into the nerve. See text for more details.
Figure 4. Compound action potentials (CAPs) evoked by conventional electrostimulation and by 12-ns PEF. (a) nsPEF elicit CAPs similar to conventional stimuli, but are selective for the excitation of fast fibers. Shown are CAP traces evoked by nsPEF at three different pulse voltages (solid lines) and by conventional stimulation (dashed line; stimulation parameters are given in the legends). Note that nsPEF at 7.2 kV elicits slightly larger response of the fastest fibers (Aα, first peak) than 250 µs, 2 V stimulation (330 and 300 µV, respectively) while the response of slower fibers (Aβ, the second peak) is 9-fold smaller (7 and 65 µV). (b) A 1-min, 100 stimuli/s tetanus using 12-ns, 11.6 kV pulses did not cause nerve damage. During the tetanus, CAP expectedly became smaller (central panel), but after a 1-min rest CAP evoked by conventional stimulation (right panel) was the same as before the stimulation (left panel; also shown by a dotted line in the right panel).
Figure 5. Tetanic stimulation (50 Hz, 1 min) by either conventional pulses or nsPEF does not change the nerve refractoriness. (a) The timeline and CAP traces from a representative experiment. Before and after each tetanus, CAPs were evoked by paired stimuli with interpulse intervals of 1, 1.5, 2, 3, and 4 ms. The tetani consisted of 3,000 single stimuli, either nsPEF (8 kV, 6.4 kV/cm) or conventional (2–4 V, 206–412 V/m), delivered with 50-ms intervals (1 min total). Shown in panels 2 and 4 are CAPs evoked by the first and the last stimuli in each tetanus (the latter CAP is smaller). See text for more details. (b) The inhibition of the test CAPs as a function of the interpulse interval, before and after tetani (open and filled symbols, respectively). The amplitude of the conditioning CAP is taken as 100%. Mean +/−  s.e., n = 8 for all groups. For clarity, error bars are shown in one direction only.
Batista Napotnik,
Effects of high voltage nanosecond electric pulses on eukaryotic cells (in vitro): A systematic review.
2016, Pubmed
Batista Napotnik,
Effects of high voltage nanosecond electric pulses on eukaryotic cells (in vitro): A systematic review.
2016,
Pubmed
Bowman,
Analysis of plasma membrane integrity by fluorescent detection of Tl(+) uptake.
2010,
Pubmed
Burton,
Effectiveness of percutaneous posterior tibial nerve stimulation for overactive bladder: a systematic review and meta-analysis.
2012,
Pubmed
Casciola,
A molecular insight into the electro-transfer of small molecules through electropores driven by electric fields.
2016,
Pubmed
Chopinet,
Nanosecond electric pulses: a mini-review of the present state of the art.
2015,
Pubmed
Cooper,
Membrane Repair: Mechanisms and Pathophysiology.
2015,
Pubmed
Craviso,
Nanosecond electric pulses: a novel stimulus for triggering Ca2+ influx into chromaffin cells via voltage-gated Ca2+ channels.
2010,
Pubmed
de Menorval,
Electric pulses: a flexible tool to manipulate cytosolic calcium concentrations and generate spontaneous-like calcium oscillations in mesenchymal stem cells.
2016,
Pubmed
D'Ostilio,
Invasive and Non-invasive Electrical Pericranial Nerve Stimulation for the Treatment of Chronic Primary Headaches.
2016,
Pubmed
Gianulis,
Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types.
2017,
Pubmed
Gianulis,
Electroporation of mammalian cells by nanosecond electric field oscillations and its inhibition by the electric field reversal.
2015,
Pubmed
Gooneratne,
Comparing neurostimulation technologies in refractory focal-onset epilepsy.
2016,
Pubmed
Ho,
Molecular dynamics simulations of ion conductance in field-stabilized nanoscale lipid electropores.
2013,
Pubmed
Ibey,
Bipolar nanosecond electric pulses are less efficient at electropermeabilization and killing cells than monopolar pulses.
2014,
Pubmed
Ibey,
Plasma membrane permeabilization by trains of ultrashort electric pulses.
2010,
Pubmed
Jacquir,
Computation of the electrical potential inside the nerve induced by an electrical stimulus.
2007,
Pubmed
Jiang,
Frequency-dependent interaction of ultrashort E-fields with nociceptor membranes and proteins.
2011,
Pubmed
Leone,
Advances in the understanding of cluster headache.
2017,
Pubmed
Nesin,
Inhibition of voltage-gated Na(+) current by nanosecond pulsed electric field (nsPEF) is not mediated by Na(+) influx or Ca(2+) signaling.
2012,
Pubmed
Oldani,
Brain stimulation treatments in bipolar disorder: A review of the current literature.
2016,
Pubmed
Pakhomov,
Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane.
2009,
Pubmed
Pakhomov,
Neuronal excitation and permeabilization by 200-ns pulsed electric field: An optical membrane potential study with FluoVolt dye.
2017,
Pubmed
Pakhomov,
Membrane permeabilization and cell damage by ultrashort electric field shocks.
2007,
Pubmed
Pakhomov,
Multiple nanosecond electric pulses increase the number but not the size of long-lived nanopores in the cell membrane.
2015,
Pubmed
Pakhomov,
Long-lasting plasma membrane permeabilization in mammalian cells by nanosecond pulsed electric field (nsPEF).
2007,
Pubmed
Pakhomov,
Search for frequency-specific effects of millimeter-wave radiation on isolated nerve function.
1997,
Pubmed
Schlenstedt,
Effect of high-frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta-analysis.
2017,
Pubmed
Schoenen,
Noninvasive neurostimulation methods for migraine therapy: The available evidence.
2016,
Pubmed
Semenov,
Electroporation by subnanosecond pulses.
2016,
Pubmed
Semenov,
Cell stimulation and calcium mobilization by picosecond electric pulses.
2015,
Pubmed
Semenov,
Diffuse, non-polar electropermeabilization and reduced propidium uptake distinguish the effect of nanosecond electric pulses.
2015,
Pubmed
Sharma,
Paradoxical loss of excitation with high intensity pulses during electric field stimulation of single cardiac cells.
2005,
Pubmed
Tolstykh,
Nanosecond pulsed electric field induced dose dependent phosphatidylinositol-4,5-bisphosphate signaling and intracellular electro-sensitization.
2017,
Pubmed
Tolstykh,
600 ns pulse electric field-induced phosphatidylinositol4,5-bisphosphate depletion.
2014,
Pubmed
Wang,
Cardiac myocyte excitation by ultrashort high-field pulses.
2009,
Pubmed
