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Emerging Trends in Neurostimulation and Neuromodulation Research

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 6693

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Special Issue Editors

Dr. Mayank Gupta

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Guest Editor

Kansas Pain Management, Overland Park, KS 66217, USA
Interests: chronic pain; pain management; neuromodulation; spinal cord stimulation; radiofrequency ablation

Dr. Brittni Levasseur

E-Mail Website
Guest Editor Assistant

Neuroscience Research Center, LLC., Overland Park, KS 66217, USA
Interests: chronic pain; pain management; neuromodulation

Special Issue Information

Dear Colleague,

The alteration of nerve activity via the target delivery of a stimulus to a precise neurological site, otherwise known as neuromodulation, has been an established clinical tool in the treatment of numerous chronic pain conditions for over fifty years and continues to grow and evolve. Electrical and magnetic stimulation are neuromodulation techniques that can be either noninvasive or invasive, such as peripheral nerve stimulation or spinal cord stimulation. Several studies have reported that nerve stimulation therapies safely and effectively provide pain relief with fewer side effects, as well as minimize the need for opioids and the utilization of healthcare resources. However, several important aspects of neuromodulation technology, such as waveform delivery and electrical programing variables, require additional research in order to optimize and personalize the stimulation to the patient’s unique pain condition. Moreover, the mechanism of action and the pathophysiology of neuromodulation need to be further investigated in order to optimize the application of nerve stimulation for more widespread conditions. Therefore, we invite researchers and investigators in their respective areas to submit both original research and review articles regarding the following topics:

Neuromodulation mechanism of action
Pathophysiology of neuromodulation
New indications and targets of nerve stimulation

Dr. Mayank Gupta
Guest Editor
Dr. Brittni Levasseur
Guest Editor Assistant

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

neuromodulation
nerve stimulation
neurostimulation waveforms
chronic pain treatment
pathophysiology

Published Papers (7 papers)

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Research

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11 pages, 1213 KiB

Open AccessArticle

Non-Invasive Radiofrequency Diathermy Neuromodulation Added to Supervised Therapeutic Exercise in Patellofemoral Pain Syndrome: A Single Blind Randomized Controlled Trial with Six Months of Follow-Up

by Manuel Albornoz-Cabello, Alfonso Javier Ibáñez-Vera, Cristo Jesús Barrios-Quinta, Luis Espejo-Antúnez, Inmaculada Carmen Lara-Palomo and María de los Ángeles Cardero-Durán

Biomedicines 2024, 12(4), 850; https://doi.org/10.3390/biomedicines12040850 - 11 Apr 2024

Viewed by 484

Abstract

The evidence-based treatment of patellofemoral pain (PFP) suggests that therapeutic exercise (TE) focused on improving muscle strength and motor control be the main conservative treatment. Recent research determined that the success of the TE approach gets improved in the short term by the addition of neuromodulation via radiofrequency diathermy (RFD). As there is no follow up data, the objective of this research is to assess the long-term effects of adding RFD to TE for the pain, function and quality of life of PFP patients. To this aim, a single-blind randomized controlled trial was conducted on 86 participants diagnosed of PFP. Participants who met the selection criteria were randomized and allocated into either a TE group or an RFD + TE group. TE consisted of a 20 min daily supervised exercise protocol for knee and hip muscle strengthening, while RFD consisted of the application of neuromodulation using a radiofrequency on the knee across 10 sessions. Sociodemographic data, knee pain and lower limb function outcomes were collected. The RFD + TE group obtained greater improvements in knee pain (p < 0.001) than the TE group. Knee function showed statistically significant improvements in Kujala (p < 0.05) and LEFS (p < 0.001) in the RFD + TE group in the short and long term. In conclusion, the addition of RFD to TE increases the beneficial effects of TE alone on PFP, effects that remain six months after treatment. Full article

(This article belongs to the Special Issue Emerging Trends in Neurostimulation and Neuromodulation Research)

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15 pages, 4350 KiB

Open AccessArticle

Structural and Functional Changes in Supraspinatus Tendinopathy through Percutaneous Electrolysis, Percutaneous Peripheral Nerve Stimulation and Eccentric Exercise Combined Therapy: A Single-Blinded Randomized Clinical Trial

by Jorge Góngora-Rodríguez, Miguel Ángel Rosety-Rodríguez, Daniel Rodríguez-Almagro, Rocío Martín-Valero, Pablo Góngora-Rodríguez and Manuel Rodríguez-Huguet

Biomedicines 2024, 12(4), 771; https://doi.org/10.3390/biomedicines12040771 - 30 Mar 2024

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Abstract

Shoulder tendinopathies produce pain and reduce functionality. The aim of this randomized clinical trial was to analyze the effects of Percutaneous electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS) and eccentric exercise (EE) on pain (NPRS), strength, electromyographic activity, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and functionality (DASH and SPADI) in individuals with supraspinatus tendinopathy. Participants (n = 50) were divided into two groups; they received 4 treatment sessions, 1 per week, of PE and PNS (n = 25) or 10 treatment sessions of TENS and US (n = 25). Both groups performed the EE program consisting of 3 sets of 10 repetitions of each of the 3 exercises, twice a day, during the 4 weeks. Follow-up was carried out at 4, 12 and 24 weeks after the start of the intervention. There are statistically significant differences in the analysis between groups (p < 0.001) in the post-treatment and follow-up measurements favorable to the PE+PNS+EE treatment on pain (NPRS), strength, supraspinatus electromyographic amplitude, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and DASH and SPADI questionnaires. The combined treatment with PE, PNS and EE is an effective option in the clinical management of tendinopathies, with positive results in the short and long term on the variables studied. Full article

(This article belongs to the Special Issue Emerging Trends in Neurostimulation and Neuromodulation Research)

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14 pages, 1966 KiB

Open AccessArticle

Development of a Cell Culture Chamber for Investigating the Therapeutic Effects of Electrical Stimulation on Neural Growth

by Quy-Susan Huynh and R. M. Damian Holsinger

Biomedicines 2024, 12(2), 289; https://doi.org/10.3390/biomedicines12020289 - 26 Jan 2024

Viewed by 828

Abstract

Natural electric fields exist throughout the body during development and following injury, and, as such, EFs have the potential to be utilized to guide cell growth and regeneration. Electrical stimulation (ES) can also affect gene expression and other cellular behaviors, including cell migration and proliferation. To investigate the effects of electric fields on cells in vitro, a sterile chamber that delivers electrical stimuli is required. Here, we describe the construction of an ES chamber through the modification of an existing lid of a 6-well cell culture plate. Using human SH-SY5Y neuroblastoma cells, we tested the biocompatibility of materials, such as Araldite^®, Tefgel™ and superglue, that were used to secure and maintain platinum electrodes to the cell culture plate lid, and we validated the electrical properties of the constructed ES chamber by calculating the comparable electrical conductivities of phosphate-buffered saline (PBS) and cell culture media from voltage and current measurements obtained from the ES chamber. Various electrical signals and durations of stimulation were tested on SH-SY5Y cells. Although none of the signals caused significant cell death, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays revealed that shorter stimulation times and lower currents minimized negative effects. This design can be easily replicated and can be used to further investigate the therapeutic effects of electrical stimulation on neural cells. Full article

(This article belongs to the Special Issue Emerging Trends in Neurostimulation and Neuromodulation Research)

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15 pages, 1031 KiB

Open AccessArticle

Transcutaneous Posterior Tibial Nerve Stimulation: An Adjuvant Treatment for Intractable Constipation in Children

by Rebeca Mayara Padilha Rego, Nilton Carlos Machado, Mary de Assis Carvalho, Johann Souza Graffunder, Crhistiano Fraguas, Erika Veruska Paiva Ortolan and Pedro Luiz Toledo de Arruda Lourenção

Biomedicines 2024, 12(1), 164; https://doi.org/10.3390/biomedicines12010164 - 12 Jan 2024

Viewed by 1397

Abstract

Background: Functional constipation can lead to painful defecations, fecal incontinence, and abdominal pain, significantly affecting a child’s quality of life. Treatment options include non-pharmacological and pharmacological approaches, but some cases are intractable and require alternative interventions like neuromodulation. A subtype of neuromodulation, called Transcutaneous Posterior Tibial Nerve Stimulation (TPTNS), comprises electrical stimulation at the ankle level, by means of electrodes fixed to the skin. TPTNS is a minimally invasive, easy-to-apply technique that can potentially improve constipation symptoms in the pediatric population by stimulating the sacral nerves. Aim: To evaluate the clinical results and applicability of TPTNS as an adjuvant treatment for children and adolescents with functional constipation. Methods: Between April 2019 and October 2021, 36 patients diagnosed with functional constipation according to the Rome IV Criteria were invited to participate in the study. The study followed a single-center, uncontrolled, prospective cohort design. Patients received TPTNS for 4 or 8 weeks, with assessments conducted immediately after the periods of TPTNS and 4 weeks after the end of the intervention period. The data normality distribution was determined by the Shapiro–Wilk test. The Wilcoxon test and Student’s t-test for paired samples were used to compare quantitative variables, and the McNemar test was used to compare categorical variables. Results: Of the 36 enrolled patients, 28 children and adolescents with intractable function constipation completed the study, receiving TPTNS for 4 weeks. Sixteen patients (57.1%) extended the intervention period for 4 extra weeks, receiving 8 weeks of intervention. TPTNS led to significant improvements in stool consistency, frequency of defecation, and bowel function scores, with a reduction in abdominal pain. Quality of life across physical and psychosocial domains showed substantial enhancements. The quality of life-related to bowel habits also improved significantly, particularly in lifestyle, behavior, and embarrassment domains. The positive effects of this intervention are seen relatively early, detected after 4 weeks of intervention, and even 4 weeks after the end of the intervention. TPTNS was well-tolerated, with an adherence rate of approximately 78%, and no adverse effects were reported. Conclusions: TPTNS is an adjuvant treatment for intractable functional constipation, improving bowel function and quality of life. The effects of TPTNS were observed relatively early and sustained even after treatment cessation. Full article

(This article belongs to the Special Issue Emerging Trends in Neurostimulation and Neuromodulation Research)

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Review

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11 pages, 452 KiB

Open AccessReview

Neuromodulation and Habituation: A Literature Review and Conceptional Analysis of Sustaining Therapeutic Efficacy and Mitigating Habituation

by Anand S. Patil, Brittni Levasseur and Mayank Gupta

Biomedicines 2024, 12(5), 930; https://doi.org/10.3390/biomedicines12050930 - 23 Apr 2024

Viewed by 455

Abstract

Spinal cord stimulation (SCS) is a therapeutic modality for the treatment of various chronic pain conditions that has rapidly evolved over the past 50 years. Unfortunately, over time, patients implanted with SCS undergo a habituation phenomenon leading to decreased pain relief. Consequently, the discovery of new stimulation waveforms and SCS applications has been shown to prolong efficacy and reduce explantation rates. This article explores various SCS waveforms, their applications, and proposes a graded approach to habituation mitigation. We suspect the neural habituation phenomenon parallels that seen in pharmacology. Consequently, we urge further exploration of the early introduction of these stimulation strategies to abate spinal cord stimulation habituation. Full article

(This article belongs to the Special Issue Emerging Trends in Neurostimulation and Neuromodulation Research)

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22 pages, 3045 KiB

Open AccessReview

Colonic Electrical Stimulation for Chronic Constipation: A Perspective Review

by Iñaki Ortego-Isasa, Juan Francisco Ortega-Morán, Héctor Lozano, Thomas Stieglitz, Francisco M. Sánchez-Margallo, Jesús Usón-Gargallo, J. Blas Pagador and Ander Ramos-Murguialday

Biomedicines 2024, 12(3), 481; https://doi.org/10.3390/biomedicines12030481 - 21 Feb 2024

Viewed by 1173

Abstract

Chronic constipation affects around 20% of the population and there is no efficient solution. This perspective review explores the potential of colonic electric stimulation (CES) using neural implants and methods of bioelectronic medicine as a therapeutic way to treat chronic constipation. The review covers the neurophysiology of colonic peristaltic function, the pathophysiology of chronic constipation, the technical aspects of CES, including stimulation parameters, electrode placement, and neuromodulation target selection, as well as a comprehensive analysis of various animal models highlighting their advantages and limitations in elucidating the mechanistic insights and translational relevance for CES. Finally, the main challenges and trends in CES are discussed. Full article

(This article belongs to the Special Issue Emerging Trends in Neurostimulation and Neuromodulation Research)

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15 pages, 1399 KiB

Open AccessReview

Transcutaneous Auricular Vagus Nerve Stimulation to Improve Emotional State

by Ainara Aranberri Ruiz

Biomedicines 2024, 12(2), 407; https://doi.org/10.3390/biomedicines12020407 - 9 Feb 2024

Viewed by 1149

Abstract

Emotional experiences are a part of our lives. The maladaptive functioning of an individual’s emotional field can lead to emotional disturbances of various kinds, such as anxiety and depression. Currently, there is an increasing prevalence of emotional disorders that cause great human suffering and high socioeconomic costs. Emotional processing has a biological basis. The major neuroscientific theories of emotion are based on biological functioning, and all of them take into account the anatomy and function of the tenth cranial nerve: the vagus nerve. The vagus nerve connects the subdiaphragmatic and supradiaphragmatic areas and modulates emotional processing as the basis of interoceptive functioning. Auricular vagus nerve stimulation is a new and innovative neuromodulation technique based on the function of the vagus nerve. Several interventions have shown that this new neurostimulation technique is a very promising resource for treating emotional disorders. In this paper, we summarise three neuroscientific theories of emotion, explain what transcutaneous auricular nerve stimulation is, and present arguments for its use and continued research. Full article

(This article belongs to the Special Issue Emerging Trends in Neurostimulation and Neuromodulation Research)

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