An experimental model of peripheral nerve electrical injury in rats.

INTRODUCTION: Although several studies have investigated models of nerve electrical injury, only a few have focused on electrical injury to peripheral nerves, which is a common and intractable problem in clinical practice. Here, we describe an experimental rat model of peripheral nerve electrical injury and its assessment. METHODS: A total of 120 animals were subjected to short-term corrective electrostimulation (50 Hz, 1-s duration) applied at varying voltages (control, 65, 75, 100, 125, and 150 V) to the exposed left sciatic nerve. Behavioural testing, electrophysiological measurements, and histopathological observation of the sciatic nerve were conducted at 1-, 2-, 4-, and 8-w follow-ups. RESULTS: No functional defects were noted in the groups that received 65-V stimulation at any time point. Sciatic nerve functional defects were found after 2 w in animals that received 75-V stimulation, but function returned to normal after 4 w. In animals that received 100-V and 125-V stimulation, functional defects were observed at 4 w, but had partially recovered by 8 w. Conversely, animals that received 150-V stimulation did not show recovery after 8 w. CONCLUSION: We presented a model of peripheral nerve electrical injury that avoided the interference of various external factors, such as current instability, compression of the surrounding tissues, and altered blood supply. The model allowed quantitation and ranking of the nerve injury into four degrees. It facilitated effective evaluation of nerve function impairment and repair after injury. It can be used post-surgically to evaluate peripheral nerve impairment and reconstruction and enables translational interpretation of results, which may improve understanding of the mechanisms underlying the progression of peripheral nerve electrical injury.

Investigation of the Neuro-Regenerative Effects of Bioresonance and Magnetotherapy in Sciatic Nerve Damage-Induced Rats / Investigación de los Efectos Neurorregenerativos de Biorresonancia y Magnetoterapia en Ratas Inducidas por Daño del Nervio Ciático

SUMMARY: Peripheral nerve damage is a significant clinical problem that can lead to severe complications in patients. Regarding the regeneration of peripheral nerves, it is crucial to use experimental animals' nerves and use different evaluation methods. Epineural or perineural suturing is the gold standard in treating sciatic nerve injury, but nerve repair is often unsuccessful. This study aimed to investigate the neuroregenerative effects of magnetotherapy and bioresonance in experimental animals with sciatic nerve damage. In this study, 24 female Wistar rats were divided into 7 groups (n=6) as follows: Group 1 (Control), Group 2 (Axonotmesis control), Group 3 (Anastomosis control), Group 4 (Axonotmesis + magnetotherapy), Group 5 (Anastomosis + magnetotherapy), Group 6 (Axonotmesis + bioresonance), Group 7 (Anastomosis + bioresonance). Magnetotherapy and bioresonance treatments were applied for 12 weeks. Behavioural tests and EMG tests were performed at the end of the 12th week. Then the rats were sacrificed, and a histopathological evaluation was made. The statistical significance level was taken as 5 % in the calculations, and the SPSS (IBM SPSS for Windows, ver.21) statistical package program was used for the calculations. Statistically significant results were obtained in animal behaviour tests, EMG, and pathology groups treated with magnetotherapy. There was no statistically significant difference in the groups treated with bioresonance treatment compared to the control groups. Muscle activity and nerve repair occurred in experimental animals with acute peripheral nerve damage due to 12 weeks of magnetotherapy, and further studies should support these results.

El daño a los nervios periféricos es un problema clínico importante que puede conducir a complicaciones graves en los pacientes. En cuanto a la regeneración de los nervios periféricos, es crucial utilizar los nervios de los animales de experimentación y diferentes métodos de evaluación. La sutura epineural o perineural es el gold estándar en el tratamiento de lesiones del nervio ciático, pero la reparación del nervio a menudo no tiene éxito. Este estudio tuvo como objetivo investigar los efectos neuroregenerativos de la magnetoterapia y la biorresonancia en animales de experimentación con daño del nervio ciático. En el estudio, 24 ratas hembras Wistar se dividieron en 7 grupos (n=6) de la siguiente manera: Grupo 1 (Control), Grupo 2 (Control de axonotmesis), Grupo 3 (Control de anastomosis), Grupo 4 (Axonotmesis + magnetoterapia), Grupo 5 (Anastomosis + magnetoterapia), Grupo 6 (Axonotmesis + biorresonancia), Grupo 7 (Anastomosis + biorresonancia). Se aplicaron durante 12 semanas tratamientos de magnetoterapia y biorresonancia. Las pruebas de comportamiento y las pruebas de EMG se realizaron al final de la semana 12. Luego se sacrificaron las ratas y se realizó una evaluación histopatológica. El nivel de significación estadística se tomó como 5 % en los cálculos, y se utilizó el programa de paquete estadístico SPSS (IBM SPSS para Windows, ver.21). Se obtuvieron resultados estadísticamente significativos en pruebas de comportamiento animal, EMG y grupos de patología tratados con magnetoterapia. No hubo diferencia estadísticamente significativa en los grupos con tratamiento de biorresonancia en comparación con los grupos controles. La actividad muscular y la reparación nerviosa, se produjeron en animales de experimentación con daño nervioso periférico agudo, debido a 12 semanas de magnetoterapia.Estudios adicionales deberían respaldar estos resultados.

Pulsed Electromagnetic Fields Improved Peripheral Nerve Regeneration After Delayed Repair of One Month.

The goal of this study was to determine if postoperative pulsed electromagnetic fields (PEMFs) could improve the neuromuscular rehabilitation after delayed repair of peripheral nerve injuries. Thirty-six Sprague-Dawley rats were randomly divided into sham group, control group, and PEMFs group. The sciatic nerves were transected except for the control group. One month later, the nerve ends of the former two groups were reconnected. PEMFs group of rats was subjected to PEMFs thereafter. Control group and sham group received no treatment. Four and 8 weeks later, morphological and functional changes were measured. Four and eight weeks postoperatively, compared to sham group, the sciatic functional indices (SFIs) of PEMFs group were higher. More axons regenerated distally in PEMFs group. The fiber diameters of PEMFs group were larger. However, the axon diameters and myelin thicknesses were not different between these two groups. The brain-derived neurotrophic factor and vascular endothelial growth factor expressions were higher in PEMFs group after 8 weeks. Semi-quantitative IOD analysis for the intensity of positive staining indicated that there were more BDNF, VEGF, and NF200 in PEMFs group. It's concluded that PEMFs have effect on the axonal regeneration after delayed nerve repair of one month. The upregulated expressions of BDNF and VEGF may play roles in this process. © 2023 Bioelectromagnetics Society.

Electroceuticals for Regeneration of Long Nerve Gap Using Biodegradable Conductive Conduits and Implantable Wireless Stimulator.

Regeneration of over 10 mm long peripheral nerve defects remains a challenge due to the failure of regeneration by prolonged axotomy and denervation occurring in long-term recovery. Recent studies reveal that conductive conduits and electrical stimulation accelerate the regeneration of long nerve defects. In this study, an electroceutical platform combining a fully biodegradable conductive nerve conduit and a wireless electrical stimulator is proposed to maximize the therapeutic effect on nerve regeneration. Fully biodegradable nerve conduit fabricated using molybdenum (Mo) microparticles and polycaprolactone (PCL) can eliminate the unwanted effects of non-degradable implants, which occupy nerve paths and need to be removed through surgery increasing the risk of complications. The electrical and mechanical properties of Mo/PCL conduits are optimized by controlling the amounts of Mo and tetraglycol lubricant. The dissolution behavior and electrical conductivity of biodegradable nerve conduits in the biomimetic solutions are also evaluated. In in vivo experiments, the integrated strategy of a conductive Mo/PCL conduit with controlled therapeutic electrical stimulation shows accelerated axon regeneration for long sciatic nerve defects in rats compared to the use of the Mo/PCL conduit without stimulation and has a significant therapeutic effect based on the results obtained from the functional recovery test.

Electrical Stimulation Induced Current Distribution in Peripheral Nerves Varies Significantly with the Extent of Nerve Damage: A Computational Study Utilizing Convolutional Neural Network and Realistic Nerve Models.

Electrical stimulation of the peripheral nervous system is a promising therapeutic option for several conditions; however, its effects on tissue and the safety of the stimulation remain poorly understood. In order to devise stimulation protocols that enhance therapeutic efficacy without the risk of causing tissue damage, we constructed computational models of peripheral nerve and stimulation cuffs based on extremely high-resolution cross-sectional images of the nerves using the most recent advances in computing power and machine learning techniques. We developed nerve models using nonstimulated (healthy) and over-stimulated (damaged) rat sciatic nerves to explore how nerve damage affects the induced current density distribution. Using our in-house computational, quasi-static, platform, and the Admittance Method (AM), we estimated the induced current distribution within the nerves and compared it for healthy and damaged nerves. We also estimated the extent of localized cell damage in both healthy and damaged nerve samples. When the nerve is damaged, as demonstrated principally by the decreased nerve fiber packing, the current penetrates deeper into the over-stimulated nerve than in the healthy sample. As safety limits for electrical stimulation of peripheral nerves still refer to the Shannon criterion to distinguish between safe and unsafe stimulation, the capability this work demonstrated is an important step toward the development of safety criteria that are specific to peripheral nerve and make use of the latest advances in computational bioelectromagnetics and machine learning, such as Python-based AM and CNN-based nerve image segmentation.

Electrochemical modulation enhances the selectivity of peripheral neurostimulation in vivo.

Electrical nerve stimulation serves an expanding list of clinical applications, but it faces persistent challenges in selectively activating bundled nerve fibers. In this study, we investigated electrochemical modulation with an ion-selective membrane (ISM) and whether it, used together with electrical stimulation, may provide an approach for selective control of peripheral nerves. Guided by theoretical transport modeling and direct concentration measurements, we developed an implantable, multimodal ISM cuff capable of simultaneous electrical stimulation and focused Ca2+ depletion. Acutely implanting it on the sciatic nerve of a rat in vivo, we demonstrated that Ca2+ depletion could increase the sensitivity of the nerve to electrical stimulation. Furthermore, we found evidence that the effect of ion modulation would selectively influence functional components of the nerve, allowing selective activation by electrical current. Our results raise possibilities for improving functional selectivity of new and existing bioelectronic therapies, such as vagus nerve stimulation.

Noninvasive Stimulation of Peripheral Nerves using Temporally-Interfering Electrical Fields.

Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation (PNS) noninvasively without surgically implanted devices are enabling for fundamental research and clinical translation. Here, it is demonstrated how relatively high-frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. This principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model is validated. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve is demonstrated. This method is simple, relying on the repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques.

A Highly Miniaturized, Chronically Implanted ASIC for Electrical Nerve Stimulation.

We present a wireless, fully implantable device for electrical stimulation of peripheral nerves consisting of a powering coil, a tuning network, a Zener diode, selectable stimulation parameters, and a stimulator IC, all encapsulated in biocompatible silicone. A wireless RF signal at 13.56 MHz powers the implant through the on-chip rectifier. The ASIC, designed in TSMC's 180 nm MS RF G process, occupies an area of less than 1.2 mm2. The IC enables externally selectable current-controlled stimulation through an on-chip read-only memory with a wide range of 32 stimulation parameters (90-750 µA amplitude, 100 µs or 1 ms pulse width, 15 or 50 Hz frequency). The IC generates the constant current waveform using an 8-bit binary weighted DAC and an H-Bridge. At the most power-hungry stimulation parameter, the average power consumption during a stimulus pulse is 2.6 mW with a power transfer efficiency of ∼5.2%. In addition to benchtop and acute testing, we chronically implanted two versions of the device (a design with leads and a leadless design) on two rats' sciatic nerves to verify the long-term efficacy of the IC and the full system. The leadless device had the following dimensions: height of 0.45 cm, major axis of 1.85 cm, and minor axis of 1.34 cm, with similar dimensions for the device with leads. Both devices were implanted and worked for experiments lasting from 21-90 days. To the best of our knowledge, the fabricated IC is the smallest constant-current stimulator that has been tested chronically.

Types of Vascular Response to Direct Intraoperative Electrical Stimulation of the Sciatic Nerve after Autoneuroplasty and Their Effect on Limb Function Recovery.

We studied different types of the vascular response to direct intraoperative low-frequency electrical stimulation of the sciatic nerve after autoneuroplasty of its tibial portion and analyzed their effects on the limb function recovery. Rats (n=20) underwent 40-min intraoperative electrical stimulation, and hemodynamics in the leg was recorded by photoplethysmography. Functional recovery of the tibial nerve was assessed using a walking path analysis within 12 weeks after surgery. Three types of the vascular response to electrical stimulation were identified: the absence of pronounced hemodynamic changes during the electrostimulation session, hyperkinetic type of hemodynamics, and venous outflow disturbances. In rats demonstrating vascular responses of types I and II during the postoperative period, the functional index of the tibial nerve partially recovered within 12 weeks; in type III, no recovery was observed. It was concluded that the type of hemodynamics during intraoperative electrical stimulation of the damaged nerve subjected to autoneuroplasty affects further restoration of the motor function of the limb.

Sonographic measures and sensory threshold of the normal sciatic nerve and hamstring muscles.

PURPOSE: The sciatic nerve innervates the hamstring muscles. Occasionally, the sciatic nerve is injured along with a hamstring muscle. Detailed biomechanical and sensory thresholds of these structures are not well-characterized. Therefore, we designed a prospective study that explored high-resolution ultrasound (US) at multiple sites to evaluate properties of the sciatic nerve, including cross-sectional area (CSA) and shear-wave elastography (SWE). We also assessed SWE of each hamstring muscle at multiple sites. Mechanical algometry was obtained from the sciatic nerve and hamstring muscles to assess multi-site pressure pain threshold (PPT). METHODS: Seventy-nine asymptomatic sciatic nerves and 147 hamstring muscles (25 males, 24 females) aged 18-50 years were evaluated. One chiropractic radiologist with 4.5 years of US experience performed the evaluations. Sciatic nerves were sampled along the posterior thigh at four sites obtaining CSA, SWE, and algometry. All three hamstring muscles were sampled at two sites utilizing SWE and algometry. Descriptive statistics, two-way ANOVA, and rater reliability were assessed for data analysis with p ≤ 0.05. RESULTS: A significant decrease in sciatic CSA from proximal to distal was correlated with increasing BMI (p < 0.001). Intra-rater and inter-rater reliability for CSA was moderate and poor, respectively. Elastographic values significantly increased from proximal to distal with significant differences in gender and BMI (p = 0.002). Sciatic PPT significantly decreased between sites 1 and 2, 1 and 3, and 1 and 4. Significant correlation between gender and PPT was noted as well as BMI (p < 0.001). Hamstring muscle elastographic values significantly differed between biceps femoris and semitendinosus (p < 0.001) and biceps femoris and semimembranosus (p < 0.001). All three hamstring muscles demonstrated increased PPT in males compared to females (p < 0.001). In addition, PPT of the biceps femoris correlated with BMI (p = 0.02). CONCLUSION: High-resolution US provided useful metrics of sciatic nerve size and biomechanical properties. PPT for the normal sciatic nerve and hamstring muscles was obtained for future clinical application.

Directed stimulation with interfascicular interfaces for peripheral nerve stimulation.

Objective.Computational models have shown that directional electrical contacts placed within the epineurium, between the fascicles, and not penetrating the perineurium, can achieve selectivity levels similar to point source contacts placed within the fascicle. The objective of this study is to test, in a murine model, the hypothesis that directed interfascicular contacts are selective.Approach.Multiple interfascicular electrodes with directional contacts, exposed on a single face, were implanted in the sciatic nerves of 32 rabbits. Fine-wire intramuscular wire electrodes were implanted to measure electromyographic (EMG) activity from medial and lateral gastrocnemius, soleus, and tibialis anterior muscles.Main results.The recruitment data demonstrated that directed interfascicular interfaces, which do not penetrate the perineurium, selectively activate different axon populations.Significance.Interfascicular interfaces that are inside the nerve, but do not penetrate the perineurium are an alternative to intrafascicular interfaces and may offer additional selectivity compared to extraneural approaches.

Stretchable, Fully Polymeric Electrode Arrays for Peripheral Nerve Stimulation.

There is a critical need to transition research level flexible polymer bioelectronics toward the clinic by demonstrating both reliability in fabrication and stable device performance. Conductive elastomers (CEs) are composites of conductive polymers in elastomeric matrices that provide both flexibility and enhanced electrochemical properties compared to conventional metallic electrodes. This work focuses on the development of nerve cuff devices and the assessment of the device functionality at each development stage, from CE material to fully polymeric electrode arrays. Two device types are fabricated by laser machining of a thick and thin CE sheet variant on an insulative polydimethylsiloxane substrate and lamination into tubing to produce pre-curled cuffs. Device performance and stability following sterilization and mechanical loading are compared to a state-of-the-art stretchable metallic nerve cuff. The CE cuffs are found to be electrically and mechanically stable with improved charge transfer properties compared to the commercial cuff. All devices are applied to an ex vivo whole sciatic nerve and shown to be functional, with the CE cuffs demonstrating superior charge transfer and electrochemical safety in the biological environment.

Stretchable, dynamic covalent polymers for soft, long-lived bioresorbable electronic stimulators designed to facilitate neuromuscular regeneration.

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.

Ultraflexible organic light-emitting diodes for optogenetic nerve stimulation.

Organic electronic devices implemented on flexible thin films are attracting increased attention for biomedical applications because they possess extraordinary conformity to curved surfaces. A neuronal device equipped with an organic light-emitting diode (OLED), used in combination with animals that are genetically engineered to include a light-gated ion channel, would enable cell type-specific stimulation to neurons as well as conformal contact to brain tissue and peripheral soft tissue. This potential application of the OLEDs requires strong luminescence, well over the neuronal excitation threshold in addition to flexibility. Compatibility with neuroimaging techniques such as MRI provides a method to investigate the evoked activities in the whole brain. Here, we developed an ultrathin, flexible, MRI-compatible OLED device and demonstrated the activation of channelrhodopsin-2-expressing neurons in animals. Optical stimulation from the OLED attached to nerve fibers induced contractions in the innervated muscles. Mechanical damage to the tissues was significantly reduced because of the flexibility. Owing to the MRI compatibility, neuronal activities induced by direct optical stimulation of the brain were visualized using MRI. The OLED provides an optical interface for modulating the activity of soft neuronal tissues.

Comparison between local infiltration analgesia with combined femoral and sciatic nerve block for pain management after total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is usually associated with moderate to severe postoperative pain. Peripheral nerve block (PNB) and local infiltration analgesia (LIA) are two major methods for postoperative analgesia. Femoral nerve block (FNB) leads to residual posterior knee pain; thus, currently sciatic nerve block (SNB) and LIA are two major options for supplementing FNB. However, the efficacy and safety of LIA compared with combined femoral and sciatic nerve block still remain controversial. Here, we conducted a study to analyze the postoperative analgesic efficacy of these two methods. METHOD: Two hundred six patients undergoing TKA were enrolled in a retrospective cohort study. The patients received either PNB or LIA. All patients in PNB group were conducted combined femoral and sciatic nerve block. All patients were encouraged to use patient-controlled analgesia (PCA) after surgery. The postoperative visual analog scale (VAS) at rest or with movement during the first 24 h and 48 h was recorded. We analyzed the VAS of 24 h, VAS of 48 h, opioid consumption, and adverse effects between PNB group and LIA group. Chi-square test and nonparametric test were used in this study. RESULTS: There were 82 patients in the PNB group and 124 patients in the LIA group. The patients' characteristics such as age, height, weight, and ASA showed no significant difference (P > 0.05). No significant differences were found (P > 0.05) between the two groups regarding VAS score at rest or with movement. The LIA group had less opioid consumption than the PNB group but without significant difference (P > 0.05). In both groups, the most common side effect was nausea, and the side effects showed no significant differences between groups (P > 0.05). CONCLUSION: Local infiltration analgesia provided a similar analgesic effect and complications compared with combined femoral and sciatic nerve block in the short term. Considering less opioid consumption with local infiltration analgesia though without significant difference and its convenience, local infiltration analgesia provided better postoperative analgesia.

Flat electrode contacts for vagus nerve stimulation.

The majority of available systems for vagus nerve stimulation use helical stimulation electrodes, which cover the majority of the circumference of the nerve and produce largely uniform current density within the nerve. Flat stimulation electrodes that contact only one side of the nerve may provide advantages, including ease of fabrication. However, it is possible that the flat configuration will yield inefficient fiber recruitment due to a less uniform current distribution within the nerve. Here we tested the hypothesis that flat electrodes will require higher current amplitude to activate all large-diameter fibers throughout the whole cross-section of a nerve than circumferential designs. Computational modeling and in vivo experiments were performed to evaluate fiber recruitment in different nerves and different species using a variety of electrode designs. Initial results demonstrated similar fiber recruitment in the rat vagus and sciatic nerves with a standard circumferential cuff electrode and a cuff electrode modified to approximate a flat configuration. Follow up experiments comparing true flat electrodes to circumferential electrodes on the rabbit sciatic nerve confirmed that fiber recruitment was equivalent between the two designs. These findings demonstrate that flat electrodes represent a viable design for nerve stimulation that may provide advantages over the current circumferential designs for applications in which the goal is uniform activation of all fascicles within the nerve.

Preparation of carboxylic graphene oxide-composited polypyrrole conduits and their effect on sciatic nerve repair under electrical stimulation.

Carboxylic graphene oxide-composited polypyrrole/poly-l-lactic acid (C-GO/PPy/PLLA) films were fabricated by electrochemical deposition of C-GO-composited PPy on PLLA fibers-film, and their conductivity and tensile strength (∼4.6 S/cm and 26.4 MPa, respectively) were stably remained after the immersion of 4 weeks, due to the hydrogen bond interaction between graphene oxide's carboxylic groups and pyrrole's imino groups. Their specific surface areas of ∼57.5 m2 /g and pore volume of ∼0.02 cm3 /g were significantly larger than those of PPy/PLLA films, due to the addition of C-GO nanosheets. Then, C-GO/PPy/PLLA conducting conduit with 2 mm inner diameter was prepared to bridge 10 mm sciatic nerve defect of rats, and the direction of fiber-axis in the conduit was the same as the conduit central axis. Electrical stimulation (ES) of 1 V and 20 Hz through the conducting conduit was exerted on the defect site. The results of in vivo electrophysiological and histological evaluation indicated that, the sciatic nerve defect could be repaired in C-GO/PPy/PLLA conduit, moreover the re-innervated gastrocnemius muscle and nerve conduction in C-GO/PPy/PLLA conduit & ES group were obviously better than the conduit without ES group. The results of transmission electron microscope analysis also demonstrated that the mean thickness of myelin sheath and diameter of axon in C-GO/PPy/PLLA conduit & ES group were significantly larger than those without ES, suggesting that the repair efficiency of ES & conduit group was closer to that of autograft group. These results indicated the great potential of C-GO/PPy/PLLA with the in vivo ES in the application of sciatic nerve repair.

Miniature electroparticle-cuff for wireless peripheral neuromodulation.

OBJECTIVE: Recent developments in peripheral nerve electrodes allow the efficient and selective neuromodulation of somatic and autonomic nerves, which has proven beneficial in specific bioelectronic medical applications. However, current most clinical devices are wired and powered by implantable batteries which suffer from several limitations. We recently developed a sub-millimeter inductively powered neural stimulator (electroparticle; EP), and in this study, we report the integration of the EP onto commercial cuff electrodes (EP-C) allowing the wireless activation of peripheral nerves. APPROACH: The current output of this device was defined at different magnetic field strenghts, and with respect to external antenna distance and activation angles. In acute in vivo testing, stimulation of the rat sciatic nerve (ScN) with the EP-C was able to evoke motor responses quantified by 3D tracking of the hind limb movement. Motor recruitment curves were obtained in response to variations in magnetic field strength (0-92.91 A m-1), stimulation frequencies (2-7 Hz), and pulse widths (50-200 µs). MAIN RESULTS: The results show constant output voltage throughout 50 400 stimulating cycles on a benchtop setting, and successful ScN motor activation with a 4 cm distance between external antenna and receiver. We achieved optimal motor recruitment indicated by maximizing range of hindlimb movement (6.01 ± 2.92 mm) with a magnetic field of 40.02 ± 2.85 A m-1 and 150 µs pulse width. Stimulating pulse width or frequency did not significantly influence motor recruitment. SIGNIFICANCE: We confirmed that continuous stimulation for 14 min using monophasic pulses did not deleteriously affect the evoked motor responses when compared to wired charge-balanced biphasic electrical stimulation. We observed, however, a 36%-44% decrease in the evoked limb movement in both groups over time due to muscle fatigue. This study shows that the EP-C device can be used effectively for peripheral nerve neuromodulation.

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.