scholarly journals ASCENT (Automated Simulations to Characterize Electrical Nerve Thresholds): A pipeline for sample-specific computational modeling of electrical stimulation of peripheral nerves

2021 ◽  
Vol 17 (9) ◽  
pp. e1009285
Author(s):  
Eric D. Musselman ◽  
Jake E. Cariello ◽  
Warren M. Grill ◽  
Nicole A. Pelot

Electrical stimulation and block of peripheral nerves hold great promise for treatment of a range of disease and disorders, but promising results from preclinical studies often fail to translate to successful clinical therapies. Differences in neural anatomy across species require different electrodes and stimulation parameters to achieve equivalent nerve responses, and accounting for the consequences of these factors is difficult. We describe the implementation, validation, and application of a standardized, modular, and scalable computational modeling pipeline for biophysical simulations of electrical activation and block of nerve fibers within peripheral nerves. The ASCENT (Automated Simulations to Characterize Electrical Nerve Thresholds) pipeline provides a suite of built-in capabilities for user control over the entire workflow, including libraries for parts to assemble electrodes, electrical properties of biological materials, previously published fiber models, and common stimulation waveforms. We validated the accuracy of ASCENT calculations, verified usability in beta release, and provide several compelling examples of ASCENT-implemented models. ASCENT will enable the reproducibility of simulation data, and it will be used as a component of integrated simulations with other models (e.g., organ system models), to interpret experimental results, and to design experimental and clinical interventions for the advancement of peripheral nerve stimulation therapies.

1962 ◽  
Vol 46 (2) ◽  
pp. 267-275 ◽  
Author(s):  
Georges Ungar ◽  
Dominick V. Romano

It was previously assumed, on the basis of changes in the ultraviolet absorption spectrum and of increase in ionizable sulfhydryl groups, that during excitation the proteins of excitable structures undergo some structural rearrangements, and these rearrangements may be similar to those designated by the term transconformation. In the present experiments, it was observed that electrical stimulation of peripheral nerves from rat, guinea pig, frog, and crab causes a decrease in their fluorescence. The peaks of the emission and activation spectra correspond to those attributed to proteins. Denaturing agents, such as urea, were also found to decrease the fluorescence of nerve extracts. It is, therefore, probable that the decrease in fluorescence, associated with the excited state, is due to a change in the configuration of the nerve proteins. The fluorescent method is applicable not only to tissue extracts but allows the observation of surviving nerve fibers before, during, and after stimulation. It showed that fluorescence of the fibers decreases invariably during stimulation and tends to return to the control level during restoration. The reduction in fluorescence is quantitatively related to the number of stimuli received by the nerve.


1981 ◽  
Vol 44 (4) ◽  
pp. 207-217 ◽  
Author(s):  
Don M. Long ◽  
Donald Erickson ◽  
James Campbell ◽  
Richard North

2003 ◽  
Vol 95 (2) ◽  
pp. 577-583 ◽  
Author(s):  
Jianhua Li ◽  
Nicholas C. King ◽  
Lawrence I. Sinoway

Previous studies have suggested that activation of ATP-sensitive P2X receptors in skeletal muscle play a role in mediating the exercise pressor reflex (Li J and Sinoway LI. Am J Physiol Heart Circ Physiol 283: H2636–H2643, 2002). To determine the role ATP plays in this reflex, it is necessary to examine whether muscle interstitial ATP (ATPi) concentrations rise with muscle contraction. Accordingly, in this study, muscle contraction was evoked by electrical stimulation of the L7 and S1 ventral roots of the spinal cord in 12 decerebrate cats. Muscle ATPi was collected from microdialysis probes inserted in the muscle. ATP concentrations were determined by the HPLC method. Electrical stimulation of the ventral roots at 3 and 5 Hz increased mean arterial pressure by 13 ± 2 and 16 ± 3 mmHg ( P < 0.05), respectively, and it increased ATP concentration in contracting muscle by 150% ( P < 0.05) and 200% ( P < 0.05), respectively. ATP measured in the opposite control limb did not rise with ventral root stimulation. Section of the L7 and S1 dorsal roots did not affect the ATPi seen with 5-Hz ventral root stimulation. Finally, ventral roots stimulation sufficient to drive motor nerve fibers did not increase ATP in previously paralyzed cats. Thus ATPi is not largely released from sympathetic or motor nerves and does not require an intact afferent reflex pathway. We conclude that ATPi is due to the release of ATP from contracting skeletal muscle cells.


1990 ◽  
Vol 68 (6) ◽  
pp. 2305-2311 ◽  
Author(s):  
J. N. Baraniuk ◽  
M. L. Kowalski ◽  
M. A. Kaliner

Electrical stimulation of rat sensory nerves produces cutaneous vasodilation and plasma protein extravasation, a phenomenon termed “neurogenic inflammation”. Rat skin on the dorsum of the paw developed neurogenic inflammation after electrical stimulation of the saphenous nerve. In tissue sections, the extravasation of the supravital dye monastral blue B identified permeable vessels. Mast cells were identified by toluidine blue stain. Permeable vessels were significantly more dense in the superficial 120 microns of the dermis than in the deeper dermis, whereas mast cells were significantly more frequent in the deeper dermis. The relationships between nociceptive sensory nerve fibers, permeable vessels, and mast cells were examined by indirect immunohistochemistry for calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and substance P (SP). CGRP-, NKA-, and SP-containing nerves densely innervated the superficial dermis and appeared to innervate the vessels that became permeable during neurogenic inflammation. In contrast, mast cells were not associated with either permeable vessels or nerve fibers. These data suggest that electrical stimulation of rat sensory nerves produces vascular permeability by inducing the release of neuropeptides that may directly stimulate the superficial vascular bed. Mast cells may not be involved in this stage of cutaneous neurogenic inflammation in rat skin.


2009 ◽  
Vol 89 (2) ◽  
pp. 181-190 ◽  
Author(s):  
Alex R Ward

Transcutaneous electrical stimulation using kilohertz-frequency alternating current (AC) became popular in the 1950s with the introduction of “interferential currents,” promoted as a means of producing depth-efficient stimulation of nerve and muscle. Later, “Russian current” was adopted as a means of muscle strengthening. This article reviews some clinically relevant, laboratory-based studies that offer an insight into the mechanism of action of kilohertz-frequency AC. It provides some answers to the question: “What are the optimal stimulus parameters for eliciting forceful, yet comfortable, electrically induced muscle contractions?” It is concluded that the stimulation parameters commonly used clinically (Russian and interferential currents) are suboptimal for achieving their stated goals and that greater benefit would be obtained using short-duration (2–4 millisecond), rectangular bursts of kilohertz-frequency AC with a frequency chosen to maximize the desired outcome.


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