Myelinated Nerve Research Articles

Lee's "Transmembrane Electrostatically-Localized Proton" model does NOT offer a better understanding of neuronal transmembrane potentials.

Recently, in a paper entitled "Protonic conductor: Better understanding [sic] neural resting and action potential," Lee applied his Transmembrane Electrostatically-Localized Protons (TELP) hypothesis to neuronal signaling. He stated that Hodgkin's cable theory "could not fully explain the different conductive patterns in unmyelinated and myelinated nerves," whereas his TELP hypothesis "enables much better understanding of neural resting/action potential and [the biological significance of] axon myelination…" However, Lee's TELP hypothesis predicts that under resting conditions, the neuron "accumulat[es] excess negative charge (anions) inside," whereas resting chloride gradients actually feature excess Cl- outside of the cell. Experiments on the neuron have shown that raising external [K+] and decreasing external [Cl-] cause membrane potential depolarization, which is predicted by the Goldman equation, but opposite to TELP hypothesis predictions. Finally, based on his TELP hypothesis, Lee predicted that the main purpose of myelin is to insulate the axonal plasma membrane specifically against proton permeability. However, he cited literature showing that myelin contains proteins that may "serve as a proton conductor with the localized protons." Thus, we show here that Lee's TELP hypothesis is highly problematic, and does NOT offer a "better understanding" of neuronal transmembrane potentials.NEW & NOTEWORTHY In this manuscript I critique a 2020 J. Neurophysiol. paper by James W. Lee. His TELP hypothesis 1) mispredicts the resting neuron's excess of external chloride; 2) predicts the preponderance of surface H+ over Na+ using ΔG° rather than ΔG; 3) mispredicts the dependence of the neuronal resting potential on external [Na+], [K+], and [Cl-]; 4) neither cites experimental results nor proposes experiments to test his hypothesis; and 5) presents a problematic characterization of the purpose of myelin.

A RhoA-mediated biomechanical response in Schwann cells modulates peripheral nerve myelination

Myelin improves axonal conduction velocity and is essential for nerve development and regeneration. In peripheral nerves, Schwann cells depend on bidirectional mechanical and biochemical signaling to form the myelin sheath but the mechanism underlying this process is not understood. Rho GTPases are integrators of “outside-in” signaling that link cytoskeletal dynamics with cellular architecture to regulate morphology and adhesion. Using Schwann cell-specific gene inactivation in the mouse, we discovered that RhoA promotes the initiation of myelination, and is required to both drive and terminate myelin growth at different stages of peripheral myelination, suggesting developmentally-specific modes of action. In Schwann cells, RhoA targets actin filament turnover, via Cofilin 1, actomyosin contractility and cortical actin-membrane attachments. This mechanism couples actin cortex mechanics with the molecular organization of the cell boundary to target specific signaling networks that regulate axon-Schwann cell interaction/adhesion and myelin growth. This work shows that RhoA is a key component of a biomechanical response required to control Schwann cell state transitions for proper myelination of peripheral nerves.

Guidance in botulinum neurotoxin injection for lower extremity spasticity: Sihler's staining technique.

Spasticity is a motor disease characterized by a velocity-dependent acceleration in muscle tone or tonic stretch reflexes linked to hypertonia. Lower limb spasticity has been successfully treated with botulinum neurotoxin; however, the injection sites have not been generalized. Sihler's stain has been used to visualize intramuscular nerve distribution to guide botulinum neurotoxin injection. Sihler staining is a whole-mount nerve staining technique that allows visualization of nerve distribution and mapping of entire nerve supply patterns in skeletal muscle with hematoxylin-stained myelinated nerve fibers. This study reviewed and summarized previous lower extremity spasticity studies to determine the ideal injection site for botulinum neurotoxin.

Role of SNAREs and Rabs in Myelin Regulation.

The myelin sheath is an insulating layer around the nerves of the brain and spinal cord which allows a fast and efficient nerve conduction. Myelin is made of protein and fatty substances and gives protection for the propagation of the electrical impulse. The myelin sheath is formed by oligodendrocytes in the central nervous system (CNS) and by Schwann cells in the peripheral nervous system (PNS). The myelin sheath presents a highly organized structure and expands both radially and longitudinally, but in a different way and with a different composition. Myelin alterations determine the onset of several neuropathies, as the electrical signal can be slowed or stopped. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and ras (rat sarcoma)-associated binding proteins (rabs) have been proved to contribute to several aspects regarding the formation of myelin or dysmyelination. Here, I will describe the role of these proteins in regulating membrane trafficking and nerve conduction, myelin biogenesis and maintenance.

Changes in myelinated fibers in the hippocampus of streptozotocin-induced diabetic rats: a stereological investigation.

Diabetes causes cognitive impairment, and the hippocampus is important for long-term and permanent memory function. However, the mechanism of their interaction is still unclear. In this study, rat models of diabetes mellitus were generated by a single injection of streptozotocin (STZ). This study aims to explore the changes in myelinated fibers in the hippocampus of type 1 diabetic rats. The unbiased stereological methods and transmission electron microscopy were used to obtain the total volume of the hippocampus, the total volume of the myelin sheath, the total length of the myelinated nerve fibers, the distribution of the length with different diameters of the myelinated fibers, and the distribution of the length with different thickness of the myelin sheath. Stereological analysis revealed that, compared to that of the control group, the total myelinated fibers volumes and the total myelinated fibers length were decreased slightly, while the total volume and the thickness of myelin sheaths were significantly decreased in the diabetic group. Finally, when compared with the control group, the total length of myelinated fibers in the diabetes group was significantly reduced, with diameters ranging from 0.7 to 1.1 μm and thicknesses of myelin sheaths from 0.15 to 0.17 μm. This study provides the first experimental evidence by stereological means to demonstrate that myelinated nerve fibers may be the key factor in cognitive dysfunction in diabetes.

Bioengineered particles expand myelin-specific regulatory T cells and reverse autoreactivity in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease characterized by autoreactive immune cells damaging myelinated nerves, impairing brain function. Treatments aim for tolerance induction to reeducate the immune system to recognize myelin as "self" rather than "foreign." As peripheral immune tolerance is primarily mediated by regulatory T cells (Tregs), we developed a therapy to support Treg expansion and activity in vivo. To target, engage, and activate myelin-specific Tregs, we designed a biodegradable microparticle (MP) loaded with rapamycin and functionalized with a biased interleukin-2 (IL-2) fusion protein and a major histocompatibility complex (MHC) class II loaded with a myelin peptide. These tolerogenic MPs (Tol-MPs) were validated in vitro and then evaluated in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Tol-MPs promoted sustained disease reversal in 100% of mice and full recovery in 38% of mice with symptomatic EAE. Tol-MPs are a promising platform for treatment of autoimmune diseases.

LncRNA Kcnq1ot1relieves neuropathic pain through downregulation of Myd88.

Long non-coding RNAs (lncRNAs) have already been documented to become the therapeutic targets for neuropathic pain. Here, this work focused on exploring the specific mechanism underlying Kcnq1 overlapping transcript 1 (kcnq1ot1) in neuropathic pain. Sciatic nerve chronic constriction injury (CCI) in vivo and LPS-stimulated microglia BV2 cell injury in vitro were adopted to construct neuropathic pain models. Expressions of kcnq1ot1, MyD88, and microglia activation marker Iba-1 were measured. In this study, we carried out fluorescence in-situ Hybridization (FISH) and immunofluorescence for examining Kcnq1ot1 localization within microglial cells in mouse spinal dorsal horn. Subsequently, we evaluated binding between Kcnq1ot1 and Myd88, together with the expressions of IL-1β, IL-6, TNF-α, and Myd88 ubiquitination. Kcnq1ot1 levels decreased within CCI mice and LPS-induced BV2 cells. According to the results of FISH and immunofluorescence, Kcnq1ot1 is located in microglia. Overexpression of Kcnq1ot1 suppressed Iba-1, IL-1β, IL-6 together with TNF-α expression. RNA pull-down and RIP assay confirmed that Kcnq1ot1 bound to Myd88. In addition, Kcnq1ot1 overexpression promoted the degradation, enhanced the ubiquitination, and reduced protein level of Myd88. Overexpression of Myd88 eliminated the effects of Kcnq1ot1 overexpression on Iba-1level and production of pro-inflammatory cytokines. Further in vivo results revealed that increased Kcnq1ot1 level alleviated neuropathic pain and myelinated nerve fiber injury of CCI mice. Kcnq1ot1 downregulated Myd88 protein expression by binding to Myd88 and promoting its ubiquitination, which in turn suppressed microglia activation, pro-inflammatory cytokine production, and relieved neuropathic pain.

Myelin histology: a key tool in nervous system research.

The myelin sheath is a lipoprotein-rich, multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers. Due to the complex structure and composition of myelin, various histological techniques have been developed over the centuries to evaluate myelin under normal, pathological or experimental conditions. Today, methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience research. In this review, we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures, from tissue fixation and processing techniques to the most used and practical myelin histological staining methods. Considering the lipoprotein nature of myelin, the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described, as well as the precise ultrastructural techniques.

Morphological Distribution Patterns and Neuroimmune Communication of Ganglia in Molly Fish (Poecilia sphenops, Valenciennes 1846)

Twenty-four adult molly fish (Poecilia sphenops, Valenciennes 1846) were collected to study the morphology and distribution of ganglia using histological, immunohistochemical, and electron microscopy and focusing on their relation to the immune cells. The ganglia were classified spatially into cranial and spinal, and functionally into sensory and autonomic. Spinal ganglia (dorsal root ganglia, DRG) contained large close ganglionic cells, enclosed by satellite cells, as well as bundles of both myelinated and non-myelinated nerve fibers. There are glial cells, immune cells and telocytes close to the ganglion. In addition, oligodendrocytes were closely related to myelinated axons. Glial fibrillary acidic protein (GFAP) expression was confined to the glia cells and the nerve fibers in the cervical ganglia next to the gills, and surprisingly, in the large ganglionic cells of the DRG. The vestibular ganglia were large, connected to the hind brain, and contained numerous neurons packed in columns. The cervical ganglia were large and observed around the pseudobranch, head kidney, and thymus. Their neurons are randomly distributed, and nerve fibers are peripherally situated. CD3-positive T-lymphocytes, dendritic cells, and CD68-positive macrophages were in close contact with the ganglia. Furthermore, the ganglia around the head kidney showed positive Iba1-expressing cells. Most ganglion cells and nerve fibers in the DRG, autonomic, and vestibular ganglia showed moderate to strong S-100 immunoreactivity. The enteric glia, CD68-expressing macrophages, and acetylcholine (Ach)-expressing neurons were observed along the muscular layer of the intestinal wall. In conclusion, different ganglia of molly fish displayed direct communication with immune cells which support and maintain healthy ganglionic cells.

In vitro myelination using explant culture of dorsal root ganglia: An efficient tool for analyzing peripheral nerve differentiation and disease modeling.

Peripheral nerves conducting motor and somatosensory signals in vertebrate consist of myelinated and unmyelinated axons. In vitro myelination culture, generated by co-culturing Schwann cells (SCs) and dorsal root ganglion (DRG) neurons, is an indispensable tool for modeling physiological and pathological conditions of the peripheral nervous system (PNS). This technique allows researchers to overexpress or downregulate molecules investigated in neurons or SCs to evaluate the effect of such molecules on myelination. In vitro myelination experiments are usually time-consuming and labor-intensive to perform. Here we report an optimized protocol for in vitro myelination using DRG explant culture. We found that our in vitro myelination using DRG explant (IVMDE) culture not only achieves myelination with higher efficiency than conventional in vitro myelination methods, but also can be used to observe Remak bundle and non-myelinating SCs, which were unrecognizable in conventional methods. Because of these characteristics, IVMDE may be useful in modeling PNS diseases, including Charcot Marie Tooth disease (CMT), in vitro. These results suggest that IVMDE may achieve a condition more similar to peripheral nerve myelination observed during physiological development.

(001) How many Nerve Fibers Innervate the Human Clitoris? A Histomorphometric Evaluation of the Dorsal Nerve of the Clitoris

Abstract Introduction It is frequently quoted in mainstream media that the clitoris has “8000 nerve endings”. However, no study has yet quantified the number of nerve fibers (axons) innervating the human clitoris. The dorsal nerve of the clitoris (DNC) is the primary source of somatic clitoral innervation. Reporting the number of axons in the DNC is an important step in our understanding of clitoral innervation and sexual response with implications for many fields of medical practice. Reconstruction following iatrogenic injuries to the dorsal clitoral nerve and restoration following cases of genital mutilation will benefit from a better understanding of the DNC. This knowledge will also be an important factor contributing to the optimization of nerve selection and sensory outcomes in gender-affirming genital surgery. Objective The purpose of this study is to quantify the number of nerve fibers in the human dorsal nerve of the clitoris (DNC) and report the approximate number of nerve fibers that innervate the human clitoris. Methods Following institutional approval and informed consent, dorsal clitoral nerve samples were obtained from 7 transmasculine patients undergoing gender-affirming phalloplasty surgery. In phalloplasty one of the two dorsal clitoral nerves is used to coapt to a sensory nerve in the phallus in order to provide for erogenous phallic sensation. At the time of nerve coaptation, a small excess of dorsal clitoral nerve (5 mm) was collected for analysis at the proximal level of the clitoral body, just after appearance of the dorsal clitoral nerve from underneath the pubic symphysis. The samples were placed into 3% glutaraldehyde fixative, post-fixed in 1% osmium tetroxide and serially dehydrate in ethanol and toluene. They were then embedded in araldite, sectioned on ultramicrotome into 1 μm cross sections and counter-stained with 1% toluidine blue. Histomorphometric evaluation was performed at 1000x magnification using a Leitz Laborlux S microscope and image analysis software (Clemex Vision Professional, Longueuil, Quebec) in order to obtain a nerve fiber count from each dorsal clitoral nerve specimen. Descriptive statistics were performed to yield a mean and range of the number of nerve fibers in the DNC. Assuming anatomic symmetry between bilateral DNC, the total number of somatic nerve fibers innervating the human clitoris was obtained by doubling the mean count of the DNC. Results 7 samples of the DNC were collected. The mean number of nerve fibers in the human dorsal clitoral nerve was 5140 with a range of 4926 to 5543. The mean number of myelinated nerve fibers innervating the human clitoris was 10281 (range 9852 to 11086). Conclusions This study is the first to report the number of myelinated nerve fibers in the human dorsal clitoral nerve and approximate the number of nerve fibers innervating the human clitoris. Findings demonstrate high and consistent myelinated axon counts and density. When taking into account the presence of uncounted unmyelinated axons, it is clear that far more than 8000 fibers innervate the human clitoris. Disclosure No

Branched-chain aminotransferase 1 promotes Schwann cell migration and proliferation to accelerate facial nerve regeneration through the Twist/FoxC1 and Sox2 pathways

Facial paralysis caused by injury to the facial nerve is common clinical presentation resulting in significant physical and psychological damage. In addition, due to the lack of understanding about the mechanisms of injury and repair and the lack of effective treatment targets, the clinical treatment outcomes for such patients remain poor. Schwann cells (SCs) have a central role in the regeneration of nerve myelin. In a rat model of facial nerves crush injury, we found that branched-chain aminotransferase 1 (BCAT1) was upregulated after injury. Moreover, it had a positive role in nerve repair. Using intervention methods such as gene knockdown, overexpression, and protein-specific inhibitors, combined with detection methods such as CCK8, Transwell, EdU, and flow cytometry, we demonstrated that BCAT1 significantly enhanced the migration and proliferation of SCs. It affected SC cell migration by regulating the Twist/Foxc1 signal axis and promoted cell proliferation by directly regulating the expression of SOX2. Similarly, animal experiments demonstrated that BCAT1 promotes facial nerve repair, improving nerve function and myelin regeneration by activating both the Twist/Foxc1 and SOX2 axes. In sum, BCAT1 promotes SC migration and proliferation, suggesting its potential as a key molecular target for improving the outcome of facial nerve injury repairs.

A biocompatible gelatin sponge scaffold confers robust tissue remodeling after spinal cord injury in a non-human primate model

We previously constructed a three-dimensional gelatin sponge (3D-GS) scaffold as a delivery vehicle for therapeutic cells and trophic factors in the treatment of spinal cord injury (SCI), and this study aimed to assess the biosafety and efficacy of the scaffold in a non-human primate SCI model. However, because it has only been tested in rodent and canine models, the biosafety and efficacy of the scaffold should ideally be assessed in a non-human primate SCI model before its use in the clinic. No adverse reactions were observed over 8 weeks following 3D-GS scaffold implantation into in a Macaca fascicularis with hemisected SCI. Scaffold implantation also did not add to neuroinflammatory or astroglial responses already present at the injured site, suggesting good biocompatibility. Notably, there was a significant reduction in α-smooth muscle actin (αSMA)-positive cells at the injury/implantation interface, leading to alleviation of fibrotic compression of the residual spinal cord tissue. The regenerating tissue in the scaffold showed numerous cells migrating into the implant secreting abundant extracellular matrix, resulting in a pro-regenerative microenvironment. Consequently, nerve fiber regeneration, myelination, vascularization, neurogenesis, and electrophysiological improvements were achieved. These results indicated that the 3D-GS scaffold had good histocompatibility and effectiveness in the structural repair of injured spinal cord tissue in a non-human primate and is suitable for use in the treatment of patients with SCI.

Myelinated Retinal Nerve Fibers, a Complicating Factor in Amblyopia Rehabilitation?

Myelinated Retinal Nerve Fibers, a Complicating Factor in Amblyopia Rehabilitation?

Gadolinium contrast agents: dermal deposits and potential effects on epidermal small nerve fibers

Small fiber neuropathy (SFN) affects unmyelinated and thinly myelinated nerve fibers causing neuropathic pain with distal distribution and autonomic symptoms. In idiopathic SFN (iSFN), 30% of the cases, the underlying aetiology remains unknown. Gadolinium (Gd)-based contrast agents (GBCA) are widely used in magnetic resonance imaging (MRI). However, side-effects including musculoskeletal disorders and burning skin sensations were reported. We investigated if dermal Gd deposits are more prevalent in iSFN patients exposed to GBCAs, and if dermal nerve fiber density and clinical parameters are likewise affected. 28 patients (19 females) with confirmed or no GBCA exposure were recruited in three German neuromuscular centers. ISFN was confirmed by clinical, neurophysiological, laboratory and genetic investigations. Six volunteers (two females) served as controls. Distal leg skin biopsies were obtained according to European recommendations. In these samples Gd was quantified by elemental bioimaging and intraepidermal nerve fibers (IENF) density via immunofluorescence analysis. Pain phenotyping was performed in all patients, quantitative sensory testing (QST) only in a subset (15 patients; 54%). All patients reported neuropathic pain, described as burning (n = 17), jabbing (n = 16) and hot (n = 11) and five QST scores were significantly altered. Compared to an equal distribution significantly more patients reported GBCA exposures (82%), while 18% confirmed no exposures. Compared to unexposed patients/controls significantly increased Gd deposits and lower z-scores of the IENF density were confirmed in exposed patients. QST scores and pain characteristics were not affected. This study suggests that GBCA exposure might alter IENF density in iSFN patients. Our results pave the road for further studies investigating the possible role of GBCA in small fiber damage, but more investigations and larger samples are needed to draw firm conclusions.

Schwannoma in the nasal cavity: A benign nerve sheath tumor at an odd location

Schwannomas are neurogenic tumors arising from the Schwann cells present in the neural sheath of the myelinated nerves. These are benign tumors that can arise anywhere in the body. Schwannomas are rarely seen in the nose and paranasal sinuses representing <4% of all head-and-neck schwannomas. Surgical excision is the treatment of choice in these cases. Nasal polyps are common nasal cavity lesions which are usually inflammatory polyps. Schwannoma of the nasal cavity usually presented with headache, unilateral nasal obstruction due to mass obliterating the nasal cavity, and epistaxis. Here, we report the case of a 47-year-old female who presented with a mass in the left nasal cavity causing the nasal blockage.

Withametelin, a steroidal lactone, isolated from datura innoxa attenuates STZ-induced diabetic neuropathic pain in rats through inhibition of NF-kB/MAPK signaling.

Diabetic neuropathic pain is one of the microvascular complications of diabetes mellitus characterized by symmetrical pain and sensory abnormalities. A steroidal lactone isolated from the datura innoxa plant, withametelin (WMT), exhibited significant neuroprotective, anti-inflammatory, antioxidant, and anticancer properties. The current study aimed to investigate anti-neuropathic pain activity and the molecular mechanism of WMT against streptozotocin (STZ)-induced diabetic neuropathy. Rats were given a single injection of STZ (60mg/kg, intraperitoneally (i.p.)) for induction of diabetes on the first day of the study. After the onset of diabetic neuropathy, pregabalin (10mg/kg, i.p.) and WMT (0.1 and 1mg/kg, i.p.) treatments were started from day 14 up to day 42. It was found that STZ-induced neuropathic pain behaviors were markedly reduced by WMT. It inhibited the STZ-associated histopathological changes and genotoxicity in the sciatic nerve and spinal cord. Additionally, Fourier transforms infrared (FTIR) spectroscopy results revealed that STZ-induced alterations in the biochemical components of the sciatic nerve's myelin sheath were inhibited by WMT. In the spinal cord, it markedly reduced the immunoreactivity of mitogen-activated protein kinases (MAPKs) signaling components such as p38-MAPK, c-Jun N-terminal kinase (JNK), extracellular-signal-regulated-kinase (ERK), and activator-protein 1 (AP-1). It also reduced the expression levels of nuclear factor-kappa-B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The production of inflammatory cytokines was considerably reduced by WMT. This study provides convincing evidence that WMT treatment attenuated STZ-induced diabetic neuropathic pain by inhibition of MAPK/NF-κB signaling.

Establishment of a Rat Model of Infraorbital Neuroinflammation Under CT Guidance.

The aim is to establish a rat model of infraorbital neuroinflammation with less trauma, stable pain, and a long duration of pain. The pathogenesis of trigeminal neuralgia (TN) is not fully clear. There are various models of TN in rats with different disadvantages, such as damaging the surrounding structures and inaccuracy of location for infraorbital nerve (ION). We aim to establish a rat model of infraorbital neuroinflammation with minimal trauma, a simple operation, and accurate positioning under CT guidance to help us study the pathogenesis of trigeminal neuralgia. Thirty-six adult male Sprague Dawley rats (180-220 g) were randomly divided into 2 groups and injected with talc suspension or saline through the infraorbital foramen (IOF) under CT guidance. Mechanical thresholds were measured in the right ION innervation region of 24 rats over 12 postoperative weeks. At 4 weeks, 8 weeks, and 12 weeks after the operation, the inflammatory involvement of the surgical area was evaluated by MRI, and neuropathy was observed using a transmission electron microscope (TEM). The talc group had a significant decrease in the mechanical threshold at 3 days after surgery that continued until 12 weeks post-operation, and the talc group had a significantly lower mechanical threshold than the saline group 10 weeks post-operation. The talc group had significantly impaired trigeminal nerve (TGN) myelin after 8 weeks post-operation. The rat model of infraorbital neuroinflammation established by CT-guided injection of talc into the IOF is a simple operation that results in less trauma, stable pain, and a long duration of pain. Moreover, infraorbital neuroinflammation in peripheral branches of the TGN can cause demyelination of the TGN in the intracranial segment.

Radial peripapillary capillary network in optic disc anomalies with abnormal tissues on disc surface.

Optic disc anomalies with abnormal tissue on the disc surface includes, myelinated nerve fiber, optic disc drusen, and Bergmeister papillae. Imaging the radial peripapillary capillary (RPC) network in optic disc anomalies with optical coherence tomography-angiography (OCTA) can give information on the RPC network in these conditions. This video describes the OCTA of optic nerve head and RPC network using the angio disc mode in cases of optic disc anomalies with abnormal tissue on the disc surface. This video presents characteristic features of RPC network in one eye each of myelinated nerve fiber, optic disc drusen, and Bergmeister papillae. OCTA in optic disc anomalies with abnormal tissue on the disc surface show a dense RPC microvascular network. OCTA is an effective imaging modality to study vascular plexus/RPC and their alteration in these disc anomalies. https://youtu.be/zlflgijy56c.

The possibility of anesthesia stimulated by a train of current pulses

This study considers a simple theoretical model of blocking the passage of signals (action potentials) from sensory neurons, thereby affecting anesthesia without the use of anesthetics as a result of a sequence of unipolar current pulses generated by an external source. The proposed model allows the selection of parameters and the required frequency of the repetition of current pulses for the possible implementation of anesthesia, depending on the electrical characteristics of the skin and the conductivity of the saline solution in which the myelinated nerve fibers are located.