Front Cardiovasc Med. 2024 May 16;11:1381721. doi: 10.3389/fcvm.2024.1381721. eCollection 2024.

ABSTRACT

The vagus nerve belongs to the parasympathetic nervous system, which is involved in the regulation of organs throughout the body. Since the discovery of the non-neuronal cardiac cholinergic system (NNCCS), several studies have provided evidence for the positive role of acetylcholine (ACh) released from cardiomyocytes against cardiovascular diseases, such as sympathetic hyperreactivity-induced cardiac remodeling and dysfunction as well as myocardial infarction. Non-neuronal ACh released from cardiomyocytes is believed to regulate key physiological functions of the heart, such as attenuating heart rate, offsetting hypertrophic signals, maintaining action potential propagation, and modulating cardiac energy metabolism through the muscarinic ACh receptor in an auto/paracrine manner. Moreover, the NNCCS may also affect peripheral remote organs (e.g., liver) through the vagus nerve. Remote ischemic preconditioning (RIPC) and NNCCS activate the central nervous system and afferent vagus nerve. RIPC affects hepatic glucose and energy metabolism through the central nervous system and vagus nerve. In this review, we discuss the mechanisms and potential factors responsible for NNCCS in glucose and energy metabolism in the liver.

PMID:38818213 | PMC:PMC11137232 | DOI:10.3389/fcvm.2024.1381721

Seizure. 2024 May 30;119:84-91. doi: 10.1016/j.seizure.2024.05.005. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies have suggested that transcutaneous vagus nerve stimulation (tVNS) may be effective for the treatment of epilepsy. However, auricular acupoint therapy (including auricular acupuncture and auricular point-sticking therapy), a method of stimulating the vagus nerve, has been poorly reviewed. This systematic review is the first to categorize auricular acupoint therapy as transcutaneous auricular vagus nerve stimulation (taVNS), aiming to assess the efficacy of taVNS in patients with epilepsy (PWE), and to analyse the results of animal experiments on the antiepileptic effects of taVNS.

METHODS: We searched MEDLINE, EMBASE, Web of Science, Scopus, and various Chinese databases from their inception to June 10, 2023 and found nine clinical studies (including a total of 788 PWE) and eight preclinical studies. We performed a meta-analysis and systematic review of these articles to assess the efficacy of taVNS in PWE and the association between taVNS and electroencephalogram (EEG) changes. We also analysed the effects on epileptic behaviour, latency of the first seizure, and seizure frequency in epileptic animals. The PRISMA 2020 checklist provided by the EQUATOR Network was used in this study.

RESULTS: taVNS had a higher response rate in PWE than the control treatment (OR = 2.94, 95 % CI = 1.94 – 4.46, P < 0.05). The analysis showed that the taVNS group showed wider EEG changes than the control group (OR = 2.17, 95 % CI 1.03 to 4.58, P < 0.05). The preclinical studies analysis revealed significant differences in epileptic behaviour (SMD = -4.78, 95 % CI -5.86 to -3.71, P < 0.05) and seizure frequency (SMD = -5.06, 95 % CI -5.96 to -4.15, P < 0.05) between the taVNS and control groups. No statistical difference was found in the latency of the first seizure between the two groups (SMD =13.54; 95 % CI 7.76 to 19.33, P < 0.05).

CONCLUSION: Based on the available data, PWE may benefit from the use of taVNS. taVNS is an effective procedure for improving epileptic behaviour in animal models.

PMID:38820674 | DOI:10.1016/j.seizure.2024.05.005

BMJ Open. 2024 May 31;14(5):e083888. doi: 10.1136/bmjopen-2024-083888.

ABSTRACT

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC).

METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 μs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events.

ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences.

TRIAL REGISTRATION NUMBER: ChiCTR2300073950.

PMID:38821572 | DOI:10.1136/bmjopen-2024-083888

Front Psychiatry. 2024 May 15;15:1397102. doi: 10.3389/fpsyt.2024.1397102. eCollection 2024.

ABSTRACT

A variety of neuromodulation treatments are available today and more are on the way, but are tomorrow’s psychiatrists prepared to incorporate these tools into their patients’ care plans? This article addresses the need for training in clinical neuromodulation for general psychiatry trainees. To ensure patient access to neuromodulation treatments, we believe that general psychiatrists should receive adequate education in a spectrum of neuromodulation modalities to identify potential candidates and integrate neuromodulation into their multidisciplinary care plans. We propose curricular development across the four FDA-cleared modalities currently available in psychiatric practice: electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). With a focus on psychiatry residency training, the article delineates core learning components for each neuromodulation technique. For each modality, we review the clinical training status, the respective FDA-cleared indications, mechanisms of action, clinical indications and contraindications, adverse effects, informed consent process, dosing considerations, and clinical management guidelines. The approach outlined in this article aims to contribute to the development of a well-rounded generation of psychiatry trainees with the capacity to navigate the growing field of neuromodulation. Whether or not a psychiatrist specializes in delivering neuromodulation therapies themselves, it is incumbent on all psychiatrists to be able to identify patients who should be referred to neuromodulation therapies, and to provide comprehensive patient care before, during and after clinical neuromodulation interventions to optimize outcomes and prevent relapse.

PMID:38812486 | PMC:PMC11133724 | DOI:10.3389/fpsyt.2024.1397102

APL Bioeng. 2024 May 28;8(2):020401. doi: 10.1063/5.0209537. eCollection 2024 Jun.

ABSTRACT

The realm of implantable bioelectronics represents a frontier in medical science, merging technology, biology, and medicine to innovate treatments that enhance, restore, or monitor physiological functions. This field has yielded devices like cochlear implants, cardiac pacemakers, deep brain stimulators, and vagus nerve stimulators, each designed to address a specific health condition, ranging from sensorineural hearing loss to chronic pain, neurological disorders, and heart rhythm irregularities. Such devices underscore the potential of bioelectronics to significantly improve patient outcomes and quality of life. Recent technological breakthroughs in materials science, nanotechnology, and microfabrication have enabled the development of more sophisticated, smaller, and biocompatible bioelectronic devices. However, the field also encounters challenges, particularly in extending the capabilities of devices such as retinal prostheses, which aim to restore vision but currently offer limited visual acuity. Research in implantable bioelectronics is highly timely, driven by an aging global population with a growing prevalence of chronic diseases that could benefit from these technologies. The convergence of societal health needs, advancing technological capabilities, and a supportive ecosystem for innovation marks this era as pivotal for bioelectronic research.

PMID:38812757 | PMC:PMC11136517 | DOI:10.1063/5.0209537

Front Pain Res (Lausanne). 2024 May 15;5:1402918. doi: 10.3389/fpain.2024.1402918. eCollection 2024.

NO ABSTRACT

PMID:38812854 | PMC:PMC11133698 | DOI:10.3389/fpain.2024.1402918

Acupunct Med. 2024 May 30:9645284241248466. doi: 10.1177/09645284241248466. Online ahead of print.

ABSTRACT

BACKGROUND: Electroacupuncture (EA) has been reported to improve intestinal motility in mice with postoperative ileus (POI). Previous studies, however, have yielded heterogeneous results regarding the effect of EA on POI.

METHODS: Herein, a POI mouse model was constructed by intestinal manipulation. To evaluate the effect of EA treatment on colonic transit, the levels of inflammatory markers (macrophage inflammatory protein (MIP)-1α, interleukin (IL)-1β, IL-6, monocyte chemotactic protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1) were detected by enzyme-linked immunosorbent assay (ELISA); immune cell infiltration was detected by immunohistochemical staining of myeloperoxidase (MPO), ectodysplasin (ED)-1 and ED-2, and the percentage of CD4⁺ interferon (IFN)-γ⁺ Th1 cells and IFN-γ secretion levels were determined. Activated Th1 cells and pentoxifylline, a cell differentiation inhibitor, were used to assess the role of Th1 cells in EA treatment of POI. Neostigmine administration and unilateral vagotomy were performed to confirm whether the effects of EA treatment on Th1 cells were mediated by the vagus nerve (VN).

RESULTS: The results revealed that EA treatment at ST36 improved POI, as indicated by a decreased level of inflammatory-related markers and immune cell infiltration and shortened colonic transit time. The activated Th1 cells abolished the effects of EA treatment on POI. The effects of EA treatment on POI were enhanced by stimulation of the VN along with a decreased level of Th1 cells, but these effects were abolished by vagotomy along with an increased percentage of Th1 cells; this result indicates that the VN mediates the role of Th1 cells in the effects of EA treatment of POI.

CONCLUSION: Our findings showed that the effects of EA treatment of POI were mainly mediated by Th1 cells through the stimulation of the VN and inhibition of the inflammatory response.

PMID:38813841 | DOI:10.1177/09645284241248466

Complement Ther Clin Pract. 2024 May 28;56:101862. doi: 10.1016/j.ctcp.2024.101862. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, human and animal studies have provided increasing evidence that vagus nerve stimulation (VNS) can produce analgesic effects as well as alleviating resistant epilepsy and depression. Our study was designed to compare the efficacy of transcutaneous auricular vagus nerve stimulation with conventional low back rehabilitation in patients with chronic low back pain (CLBP).

METHODS: Sixty patients with LBP were randomly divided into two groups. Group 1 received conventional rehabilitation and home exercise, and Group 2 received transcutaneous auricular VNS and home exercise. Both groups received treatment five days a week for three weeks. Trunk mobility (Modified Schober test, fingertip-to-floor test), muscle strength (CSMI-Cybex Humac-Norm isokinetic dynamometer and Lafayette manual muscle strength measuring device), trunk endurance, balance tests, Visual Analog Scale, Beck Depression Scale, Pittsburgh Sleep Quality Index, Oswestry Disability Index were evaluated.

RESULTS: At the end of three weeks, within-group assessment results showed positive effects on mobility, functional status, depression and sleep in all groups (p < 0.05). Pain level, endurance time and flexion trunk muscle strength results showed more improvement in Group 2 (p < 0.05). Some parameters of isokinetic lower extremity quadriceps muscle strength and fall risk scores showed a significant improvement in Group 1 (p < 0.05).

DISCUSSION: VNS has been observed to be more effective on pain, trunk muscle strength and endurance duration and sleep status. Auricular VNS may be included in the treatment of patients with CLBP in whom conventional physical therapy is inadequate or not applicable.

PMID:38815433 | DOI:10.1016/j.ctcp.2024.101862

Arch Phys Med Rehabil. 2024 May 28:S0003-9993(24)01014-1. doi: 10.1016/j.apmr.2024.05.018. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate differences in upper extremity (UE) segment-specific (proximal or distal segment) recovery after Vagus nerve stimulation (VNS) paired with UE rehabilitation (Paired-VNS) compared to rehabilitation with sham-VNS (Control). We also assessed whether gains in specific UE segments predicted clinically meaningful improvement.

DESIGN: This study reports on a secondary analysis of the randomized, triple-blinded, sham-controlled pivotal VNS-REHAB trial. A Rasch latent regression was used to determine differences between Paired-VNS and Controls for distal and proximal UE changes after in-clinic therapy and 3-months later. Subsequently, we ran a random forest model to assess candidate predictors of meaningful improvement. Each item of the Fugl-Meyer Assessment-Upper Extremity and Wolf Motor Function Test was evaluated as a predictor of response to treatment.

SETTING: Data analyzed in this study were obtained from the completed VNS-REHAB trial. Participants received intensive UE rehabilitation from physical and occupational therapists in an outpatient setting for 6 weeks, followed by a home-based exercise program.

PARTICIPANTS: Dataset included 108 participants with chronic ischemic stroke and moderate-to-severe UE impairments.

INTERVENTIONS: N/A MAIN OUTCOME MEASURES: Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT) RESULTS: Distal UE improvement was significantly greater in the Paired-VNS group compared to Controls immediately post-therapy (95% CI [0.27-0.73], p≤0.001) and after 3-months (95% CI [0.16-0.75], p=0.003). Both groups showed similar improvement in proximal UE at both time points. A subset of both distal and proximal items from the FMA-UE and WMFT were predictors of meaningful improvement.

CONCLUSIONS: Paired-VNS improved distal UE impairment in chronic stroke to a greater degree than intensive rehabilitation alone. Proximal improvements were equally responsive to either treatment. Given that meaningful UE recovery is predicted by improvements across both proximal and distal segments, Paired-VNS may facilitate improvement that is otherwise elusive.

PMID:38815953 | DOI:10.1016/j.apmr.2024.05.018

Medicina (Kaunas). 2024 Apr 27;60(5):729. doi: 10.3390/medicina60050729.

ABSTRACT

Background and Objectives: This review systematically evaluates the potential of electrical neuromodulation techniques-vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial nerve stimulation (TNS)-as alternative treatments for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s Disease (CD). It aims to synthesize current evidence on the efficacy and safety of these modalities, addressing the significant burden of IBD on patient quality of life and the limitations of existing pharmacological therapies. Materials and Methods: We conducted a comprehensive analysis of studies from PubMed, focusing on research published between 1978 and 2024. The review included animal models and clinical trials investigating the mechanisms, effectiveness, and safety of VNS, SNS, and TNS in IBD management. Special attention was given to the modulation of inflammatory responses and its impact on gastrointestinal motility and functional gastrointestinal disorders associated with IBD. Results: Preliminary findings suggest that VNS, SNS, and TNS can significantly reduce inflammatory markers and improve symptoms in IBD patients. These techniques also show potential in treating related gastrointestinal disorders during IBD remission phases. However, the specific mechanisms underlying these benefits remain to be fully elucidated, and there is considerable variability in treatment parameters. Conclusions: Electrical neuromodulation holds promise as a novel therapeutic avenue for IBD, offering an alternative to patients who do not respond to traditional treatments or experience adverse effects. The review highlights the need for further rigorous studies to optimize stimulation parameters, understand long-term outcomes, and integrate neuromodulation effectively into IBD treatment protocols.

PMID:38792911 | DOI:10.3390/medicina60050729