Evaluation of Activated Carbon and Platinum Black as High-Capacitance Materials for Platinum Electrodes.

The application of direct current (DC) produces a rapid and reversible nerve conduction block. However, prolonged injection of charge through a smooth platinum electrode has been found to cause damage to nervous tissue. This damage can be mitigated by incorporating high-capacitance materials (HCM) (e.g., activated carbon or platinum black) into electrode designs. HCMs increase the storage charge capacity (i.e., "Q value") of capacitive devices. However, consecutive use of these HCM electrodes degrades their surface. This paper evaluates activated carbon and platinum black (PtB) electrode designs in vitro to determine the design parameters which improve surface stability of the HCMs. Electrode designs with activated carbon and PtB concentrations were stressed using soak, bend and vibration testing to simulate destructive in vivo environments. A Q value decrease represented the decreased stability of the electrode-HCM interface. Soak test results supported the long-term Q value stabilization (mean = 44.3 days) of HCM electrodes, and both HCMs displayed unique Q value changes in response to soaking. HCM material choices, Carbon Ink volume, and application of Nafion™ affected an electrode's ability to resist Q value degradation. These results will contribute to future developments of HCM electrodes designed for extended DC application for in vivo nerve conduction block.

Does patterned afferent stimulation of sacral dermatomes suppress urethral sphincter reflexes in individuals with spinal cord injury?

AIMS: Dyssynergic contractions of the external urethral sphincter prevent efficient bladder voiding and lead to numerous health concerns. Patterned electrical stimulation of the sacral dermatomes reduces urethral sphincter spasms and allows functional bladder emptying in cats after chronic SCI. Reflex suppression in animals is strongly dependent on stimulus location and pattern. The purpose of this study was to determine whether the stimulation patterns and locations effective in animals suppress urethral sphincter spasms in humans with SCI. METHODS: Ten subjects with chronic SCI underwent bladder filling to elicit distention-evoked contractions. During reflex contractions patterned electrical stimulation was applied to the S2 or S3 dermatome in random 25-sec intervals. Bladder and sphincter pressures were simultaneously recorded and compared between control and afferent stimulation periods. RESULTS: Six of the 10 subjects demonstrated both reflex bladder and sphincter contractions with bladder filling. No significant reduction in urethral pressure was observed during stimulation for any stimulus locations and patterns tested. CONCLUSIONS: Stimulation parameters and locations effective in SCI animals did not suppress reflex sphincter activity in these human subjects. It is likely that a broader set of stimulus patterns and dermatome locations will need to be tested to find the effective combination in humans.

Electrical stimulation of sacral dermatomes can suppress aberrant urethral reflexes in felines with chronic spinal cord injury.

AIMS: Uncoordinated reflex contractions of the external urethral sphincter (EUS) are a major component of voiding dysfunction after neurologic injury. Patterned stimulation of sacral afferent pathways can reduce abnormal EUS reflexes after acute spinal cord injury (SCI); however, effectiveness following chronic SCI is unknown. METHODS: Four adult male cats were implanted with bilateral extradural sacral root electrodes to allow bladder activation and underwent subsequent spinal transection (T10-12). Nine weeks after SCI urethral and bladder pressures were recorded with and without sacral afferent stimulation. Surface electrodes were applied to sacral and lumbar dermatomes and stimulus amplitude set below the muscle fasciculation threshold. The stimulation pattern was varied by on/off times of fixed frequency at each location. RESULTS: Reflexive EUS contractions were observed in all animals after chronic SCI. Patterned sacral dermatome stimulation reduced EUS reflex rate and amplitude in two of four cats. Suppression was dependent on both the stimulus location and pattern. Sacral locations and a stimulation pattern of (0.75 sec on, 0.25 sec off, 20 Hz) were effective in both responder animals. CONCLUSIONS: Patterned sacral dermatome stimulation can reduce abnormal urethral reflexes following chronic SCI. Reflex suppression is dependent on both the stimulation location and stimulus pattern. Reduction of reflexive EUS activity after chronic SCI with this non-destructive and non-invasive approach may provide an advance for the treatment of detrusor-sphincter-dyssynergia.

High frequency sacral root nerve block allows bladder voiding.

AIMS: Dyssynergic reflexive external urethral sphincter (EUS) activity following spinal cord injury can prevent bladder voiding, resulting in significant medical complications. Irreversible sphincterotomies or neurotomies can prevent EUS activation and allow bladder voiding, but may cause incontinence or loss of sacral reflexes. We investigated whether kilohertz frequency (KF) electrical conduction block of the sacral roots could prevent EUS activation and allow bladder voiding. METHODS: The S2 sacral nerve roots were stimulated bilaterally to generate bladder pressure in six cats. One S1 nerve root was stimulated proximally (20 Hz biphasic pulse trains) to evoke EUS pressure, simulating worst-case dyssynergic EUS reflexes. KF waveforms (12.5 kHz biphasic square wave) applied to an electrode implanted distally on the S1 nerve root blocked nerve conduction, preventing the increase in EUS pressure and allowing voiding. RESULTS: Applying KF waveforms increased bladder voiding in single, limited-duration trials from 3 ± 6% to 59 ± 12%. Voiding could be increased to 82 ± 9% of the initial bladder volume by repeating or increasing the duration of the trials. CONCLUSIONS: Sacral nerve block can prevent EUS activation and allow complete bladder voiding, potentially eliminating the need for a neurotomy. Eliminating neurotomy requirements could increase patient acceptance of bladder voiding neuroprostheses, increasing patient quality of life and reducing the cost of patient care.

Suppression of reflex urethral responses by sacral dermatome stimulation in an acute spinalized feline model.

AIMS: Reflex contractions of the external urethral sphincter (EUS) are a major component of voiding dysfunction after neurological injury or disease. Aberrant urethral reflexes can prevent voiding and cause serious medical complications. Characterizing these urethral reflexes during genitourinary studies is necessary for evaluating novel pharmacological or neuroprosthetic approaches. The objectives of the present study were to generate urethral reflexes in the acute spinal feline, to quantify these reflexes, and to suppress them with electrical stimulation of the sacral dermatomes. METHODS: This study comprised eight male cats. Anaesthesia was maintained with alpha-chloralose or sodium pentobarbital. The spinal cord was transected between T10 and T12, and nerve cuff electrodes were placed on the extradural S2 sacral roots to provide bladder activation. Bladder and urethral pressures were recorded during and after bladder contractions. Electrical stimulation was applied non-invasively to the sacral dermatomes with commercial surface electrodes. RESULTS: Urethral reflexes were elicited consistently in six cats. The corresponding urethral pressure spikes were quantified. Putative metrics of urethral reflex activity such as the rate and average magnitude of reflex pressure spikes correlated significantly with standard urodynamic variables. Electrical stimulation of the sacral dermatomes suppressed urethral reflexes in three cats. CONCLUSIONS: These findings in an acute spinal feline preparation demonstrate a non-invasive means of suppressing undesirable urethral reflexes. Translation of this work to clinical use could improve neuroprostheses for restoring bladder function and enhance treatment of aberrant urethral reflexes in humans.

Intraurethral stimulation for reflex bladder activation depends on stimulation pattern and location.

AIMS: Reflex bladder excitation has been demonstrated by stimulation of the pudendal nerve and several of its distal branches. However, excitation parameters have not been consistent and the relationship to anatomical locations within the urethra has not been fully investigated. An improved understanding of the lower urinary tract neurophysiology will improve human studies and neuroprosthetic device development. METHODS: Intraurethral stimulation was performed in nine cats at near isovolumetric bladder volumes before and/or after spinalization. Bladder excitability profiles were obtained for lower (2 Hz) and higher (33 Hz) frequency stimuli along the urethra between the bladder neck and external meatus. RESULTS: Higher frequency stimuli were excitable at all urethral locations prior to spinalization but only excitable in the middle and distal urethra after spinalization. Lower frequency stimuli were excitable at proximal and middle locations before spinalization but not excitable at any location after spinalization. In most evaluations, bursting pulse stimulation patterns evoked greater bladder pressures than the dominant continuous frequency (2 or 33 Hz). CONCLUSIONS: These data indicate the potential presence of two distinct pathways for reflex bladder activation within the urethra: a supra-T10 circuit initiated in the proximal and mid urethra that responds to lower and higher frequency stimuli, and a sacral circuit initiated in the mid and distal urethra that responds to higher frequency stimuli. This work suggests potential anatomical targets and stimulus patterns for clinical evaluations of peripheral nerve-based neuroprostheses for bladder control.

Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first, charge-imbalanced, biphasic pulses for 0.566 ⩽ k ⩽ 2.3 in rat subcutaneous tissues.

OBJECTIVE: Charge injection through platinum neural stimulation electrodes is often constrained by the Shannon limit (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6) of k = 1.75. By leveraging the tools of electrochemistry to better understand the reactions at electrode-tissue interface, we endeavor to find a way to safely inject more charge than allowed if the traditional Shannon limit were followed. APPROACH: In previous studies on platinum electrodes using charge-balanced, cathodic-first, biphasic pulses, we noted that during the secondary anodic phase, the electrode potential moves into a range where platinum dissolution is possible when charge injection is greater than k = 1.75. Platinum dissolution products are known to be toxic to brain tissues. We hypothesize that by injecting less charge in the anodic phase than the cathodic phase, the anodic potential excursions will decrease, thereby avoiding potentials where platinum dissolution is more likely. MAIN RESULTS: Our findings show that using these charge-imbalanced pulses decreases the anodic potential excursions to a level where platinum oxidation and dissolution are less likely, and aligns the anodic potentials with those observed with charge-balanced stimulation at k < 1.75-a range widely accepted as safe for stimulation with platinum. SIGNIFICANCE: From these results, we further hypothesize that charge-imbalanced biphasic stimulation would permit more charge to be safely injected through platinum electrodes than would be permitted if the dogma of charge-balanced biphasic stimuli were followed. Testing this hypothesis in cat brain in the same manner as the experiments that formed the basis for the Shannon plot could open the door for safe charge injection through platinum electrodes at levels greater than k = 1.75.

Measurement of block thresholds in kiloHertz frequency alternating current peripheral nerve block.

BACKGROUND: Kilohertz frequency alternating currents (KHFAC) produce rapid nerve conduction block of mammalian peripheral nerve and have potential clinical applications in reducing peripheral nerve hyperactivity. The experimental investigation of KHFAC nerve block requires a robust output measure and this has proven to be the block threshold (BT), the lowest current or voltage at which the axons of interest are completely blocked. All significant literature in KHFAC nerve block, both simulations and experimental, were reviewed to determine the block threshold method that was used. The two common methods used are the High-Low method experimentally and the Binary search method for simulations. NEW METHOD: Four methods to measure the block threshold (High-Low, High-Low-High, Binary and Random) at three frequencies (10, 20 and 30 kHz) were compared through randomized repeated experiments in the in-vivo rodent sciatic nerve-gastrocnemius model. RESULTS: The literature review showed that more than 50% of publications did not measure the block threshold. The experimental results showed no statistical difference in the BT value between the four methods. COMPARISON WITH EXISTING METHOD(S): However, there were differences in the number of significant onset responses, depending on the method. The run time for the BT determination was the shortest for the High-Low method. CONCLUSIONS: It is recommended that all research in electrical nerve block, including KHFAC, should include measurement of the BT. The High-Low method is recommended for most experimental situations but the Binary method could also be a viable option, especially where onset responses are minimal.

A Carbon Slurry Separated Interface Nerve Electrode for Electrical Block of Nerve Conduction.

Direct current (DC) nerve block has been shown to provide a complete block of nerve conduction without unwanted neural firing. Previous work shows that high capacitance electrodes can be used to safely deliver a DC block. Another way of delivering DC safely is through a separated interface nerve electrode (SINE), such that any reactive species that are generated by the passage of DC are contained in a vessel away from the nerve. This design has been enhanced by using a high capacitance carbon "slurry" as the electrode in the external vessel to extend the capacity of the electrode (CSINE). With this new design, it was possible to provide 50 min of continuous nerve block without recharge while still maintaining complete recovery of neural signals. Up to 46 C of charge delivery was applied for a total of 4 h of nerve block with complete recovery. Because of the extended delivery time, it was possible to explore several properties of DC block that would not be revealed without the capability of a long-duration continuous block. It was possible to achieve complete block at lower values of DC if the block was applied for a longer period of time. Depending on the amount of charge applied during the block, the recovery was delayed for a period of time before complete force recovery was restored. These new properties provide novel techniques for device development to optimize charge delivery time and device powering concerns.

Variable patterned pudendal nerve stimuli improves reflex bladder activation.

We evaluated variable patterns of pudendal nerve (PN) stimuli for reflex bladder excitation. Reflex activation of the bladder has been demonstrated previously with 20-33 Hz continuous stimulation of PN afferents. Neuronal circuits accessed by afferent mediated pathways may respond better to physiological patterned stimuli than continuous stimulation. Unilateral PN nerve cuffs were placed in neurologically intact male cats. PN stimulation (0.5-100 Hz) was performed under isovolumetric conditions at bladder volumes up to the occurrence of distension evoked reflex contractions. Stimulus evoked reflex bladder contractions were elicited in eight cats. Across all experiments, bursting of 2-10 pulses at 100-200 Hz repeated at continuous stimulation frequencies evoked significantly larger bladder responses than continuous (single pulse) stimulation (52.0+/-44.5%). Bladder excitation was also effective at 1 Hz continuous stimuli, which is lower than typically reported. Variable patterned pulse bursting resulted in greater evoked reflex bladder pressures and increased the potential stimulation parameter space for effective bladder excitation. Improved bladder excitation should increase the efficacy of neuroprostheses for bladder control.

Temporary persistence of conduction block after prolonged kilohertz frequency alternating current on rat sciatic nerve.

OBJECTIVE: Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve conduction block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5-10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes. APPROACH: Varying durations of KHFAC at signal amplitudes for conduction block with intervals of no stimulus were studied. Nerve conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a blocking electrode. The PS signal traveled through the block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of conduction patency of the nerve in the block zone. MAIN RESULTS: Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-block levels for cumulative stimulus of 50 ± 20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60-80% recovery), followed by a slower phase. No permanent conduction block was seen at the end of the observation period during any experiment. SIGNIFICANCE: This carry-over block effect may be exploited to provide continuous conduction block in peripheral nerves without continuous application of KHFAC.

Reversible conduction block in peripheral nerve using electrical waveforms.

INTRODUCTION: Electrical nerve block uses electrical waveforms to block action potential propagation. MATERIALS & METHODS: Two key features that distinguish electrical nerve block from other nonelectrical means of nerve block: block occurs instantly, typically within 1 s; and block is fully and rapidly reversible (within seconds). RESULTS: Approaches for achieving electrical nerve block are reviewed, including kilohertz frequency alternating current and charge-balanced polarizing current. We conclude with a discussion of the future directions of electrical nerve block. CONCLUSION: Electrical nerve block is an emerging technique that has many significant advantages over other methods of nerve block. This field is still in its infancy, but a significant expansion in the clinical application of this technique is expected in the coming years.

Continuous Direct Current Nerve Block Using Multi Contact High Capacitance Electrodes.

Charge-balanced direct current (CBDC) nerve block can be used to block nerve conduction in peripheral nerves. Previous work demonstrated that the CBDC waveform could be used to achieve a 10% duty cycle of block to non-block repeatedly for at least two hours. We demonstrate that the duty cycle of this approach can be significantly increased by utilizing multiple electrode contacts and cycling the CBDC waveform between each contact in a "carousel" configuration. Using this approach, we demonstrated in an acute rat sciatic nerve preparation, that a 30% duty cycle complete block can be achieved with two contacts; and a 100% duty cycle block (>95% complete block) can be achieved with four contacts. This latter configuration utilized a 4-s block plateau, with 3 s between successive plateaus at each contact and a recharge phase amplitude that was 34% of the block amplitude. Further optimization of the carousel approach can be achieved to improve block effectiveness and minimize total electrode length. This approach may have significant clinical use in cases where a partial or complete block of peripheral nerve activity is required. In one example case, we achieved continuous block for 22 min without degradation of nerve conduction. Future study will be required to further optimize this technique and to demonstrate safety for chronic human use.

Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first, charge-balanced, biphasic pulses for 0.566 ⩽ k ⩽ 2.3 in rat subcutaneous tissues.

OBJECTIVE: Our mission is twofold: (1) find a way to safely inject more charge through platinum electrodes than the Shannon limit (k = 1.75) permits and (2) nurture an interest in the neural stimulation community to understand the electron transfer process occurring on neural stimulating electrodes. APPROACH: We report here on measurements of the electrode potential, performed on platinum neural stimulating electrodes in the subcutaneous space of an anesthetized rat under neural stimulation conditions. MAIN RESULTS: The results for six platinum electrodes with areas ranging from 0.2 mm2 to 12.7 mm2 were similar to prior results in sulfuric acid, except that the measured potentials were shifted negative 0.36 V because of the pH difference between the two media. The anodic 'end' potential, measured at t = 20 ms after the onset of the biphasic current pulse, was the primary focus of the data collected because previous results had shown that as charge injection crosses the Shannon limit (k = 1.75), this potential moves into a range where platinum surface oxidation and dissolution is likely to occur. The behavior of V e(t = 20 ms) over a range of electrode surface areas studied was consistent with our sulfuric acid study. Implicit, but little noticed, in Shannon's formulation is that small and large platinum electrodes behave the same in terms of k value; our data supports this idea. SIGNIFICANCE: We hypothesize that the k = 1.75 Shannon limit for safe stimulation designates a charge-injection boundary above which platinum toxicity becomes a relevant consideration for living cells around an electrode, a possibility that can be directly tested, and is a vital step forward in mission (1).

High frequency electrical conduction block of the pudendal nerve.

A reversible electrical block of the pudendal nerves may provide a valuable method for restoration of urinary voiding in individuals with bladder-sphincter dyssynergia. This study quantified the stimulus parameters and effectiveness of high frequency (HFAC) sinusoidal waveforms on the pudendal nerves to produce block of the external urethral sphincter (EUS). A proximal electrode on the pudendal nerve after its exit from the sciatic notch was used to apply low frequency stimuli to evoke EUS contractions. HFAC at frequencies from 1 to 30 kHz with amplitudes from 1 to 10 V were applied through a conforming tripolar nerve cuff electrode implanted distally. Sphincter responses were recorded with a catheter mounted micro-transducer. A fast onset and reversible motor block was obtained over this range of frequencies. The HFAC block showed three phases: a high onset response, often a period of repetitive firing and usually a steady state of complete or partial block. A complete EUS block was obtained in all animals. The block thresholds showed a linear relationship with frequency. HFAC pudendal nerve stimulation effectively produced a quickly reversible block of evoked urethral sphincter contractions. The HFAC pudendal block could be a valuable tool in the rehabilitation of bladder-sphincter dyssynergia.

Characterization of high capacitance electrodes for the application of direct current electrical nerve block.

Direct current (DC) can briefly produce a reversible nerve conduction block in acute experiments. However, irreversible reactions at the electrode-tissue interface have prevented its use in both acute and chronic settings. A high capacitance material (platinum black) using a charge-balanced waveform was evaluated to determine whether brief DC block (13 s) could be achieved repeatedly (>100 cycles) without causing acute irreversible reduction in nerve conduction. Electrochemical techniques were used to characterize the electrodes to determine appropriate waveform parameters. In vivo experiments on DC motor conduction block of the rat sciatic nerve were performed to characterize the acute neural response to this novel nerve block system. Complete nerve motor conduction block of the rat sciatic nerve was possible in all experiments, with the block threshold ranging from -0.15 to -3.0 mA. DC pulses were applied for 100 cycles with no nerve conduction reduction in four of the six platinum black electrodes tested. However, two of the six electrodes exhibited irreversible conduction degradation despite charge delivery that was within the initial Q (capacitance) value of the electrode. Degradation of material properties occurred in all experiments, pointing to a possible cause of the reduction in nerve conduction in some platinum black experiments .

Electron transfer processes occurring on platinum neural stimulating electrodes: a tutorial on the i(V e) profile.

The aim of this tutorial is to encourage members of the neuroprosthesis community to incorporate electron transfer processes into their thinking and provide them with the tools to do so when they design and work with neurostimulating devices. The focus of this article is on platinum because it is the most used electrode metal for devices in commercial use. The i(V e) profile or cyclic voltammogram contains information about electron transfer processes that can occur when the electrode-electrolyte interface, V e, is at a specific potential, and assumed to be near steady-state conditions. For the engineer/designer this means that if the potential is not in the range of a specific electron transfer process, that process cannot occur. An i(V e) profile, recorded at sweep rates greater than 0.1 mVs(-1), approximates steady-state conditions. Rapid transient potential excursions, like that seen with neural stimulation pulses, may be too fast for the reaction to occur, however, this means that if the potential is in the range of a specific electron transfer process it may occur and should be considered. The approach described here can be used to describe the thermodynamic electron transfer processes on other candidate electrode metals, e.g. stainless steel, iridium, carbon-based, etc.

Direct current contamination of kilohertz frequency alternating current waveforms.

Kilohertz frequency alternating current (KHFAC) waveforms are being evaluated in a variety of physiological settings because of their potential to modulate neural activity uniquely when compared to frequencies in the sub-kilohertz range. However, the use of waveforms in this frequency range presents some unique challenges regarding the generator output. In this study we explored the possibility of undesirable contamination of the KHFAC waveforms by direct current (DC). We evaluated current- and voltage-controlled KHFAC waveform generators in configurations that included a capacitive coupling between generator and electrode, a resistive coupling and combinations of capacitive with inductive coupling. Our results demonstrate that both voltage- and current-controlled signal generators can unintentionally add DC-contamination to a KHFAC signal, and that capacitive coupling is not always sufficient to eliminate this contamination. We furthermore demonstrated that high value inductors, placed in parallel with the electrode, can be effective in eliminating DC-contamination irrespective of the type of stimulator, reducing the DC contamination to less than 1 µA. This study highlights the importance of carefully designing the electronic setup used in KHFAC studies and suggests specific testing that should be performed and reported in all studies that assess the neural response to KHFAC waveforms.

Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block.

OBJECTIVE: Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. APPROACH: A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. MAIN RESULTS: The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p < 0.001). The area under the force curve was reduced from 6.8 Ns (range: 3.5-21.9 Ns) to 0.54 Ns (range: 0.18-0.86 Ns) (p < 0.01). No change in nerve conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. SIGNIFICANCE: The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity.

Alternating current and infrared produce an onset-free reversible nerve block.

Nerve block can eliminate spasms and chronic pain. Kilohertz frequency alternating current (KHFAC) produces a safe and reversible nerve block. However, KHFAC-induced nerve block is associated with an undesirable onset response. Optical inhibition using infrared (IR) laser light can produce nerve block without an onset response, but heats nerves. Combining KHFAC with IR inhibition [alternating current and infrared (ACIR)] produces a rapidly reversible nerve block without an onset response. ACIR can be used to rapidly and reversibly provide onset-free nerve block in the unmyelinated nerves of the marine mollusk Aplysia californica and may have significant advantages over either modality alone. ACIR may be of great clinical utility in the future.