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

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

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

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

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

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 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

Epilepsy Res. 2024 May 21;203:107383. doi: 10.1016/j.eplepsyres.2024.107383. Online ahead of print.

ABSTRACT

The aim of this single-centre, retrospective, observational study was to evaluate long-term effectiveness of vagus nerve stimulation (VNS) in drug-resistant epilepsy (DRE) by using retention rate as a surrogate measure for seizure reduction. We included all patients with DRE, treated at the adult neurology department of the University Hospitals Leuven and who started VNS therapy from January 1, 1994, until May 1, 2021, with follow-up data cutoff on January 1, 2023. Retention rate of VNS was defined as the percentage of patients who maintain VNS at established time points. We estimated cumulative retention rate and battery replacement rate and correlated these with seizure reduction, using Kaplan-Meier analysis. Statistical analysis of potential predictors of VNS outcome (age, sex and epilepsy duration at implantation) was performed using mono- and multivariate analyses. VNS was started in 110 patients with DRE, with a mean follow-up of 8.7 years (SD 6.5). VNS was discontinued in 55 patients (50%), with ineffectiveness as the main reason for discontinuation (98%). The battery was replaced at least once in 42 patients (38%). Estimated retention rates were 70%, 52%, 45% and 33% after 5, 10, 15 and 20 years, respectively. Estimated first battery replacement rates were 16%, 42% and 47% after 5, 10 and 15 years, respectively. Both estimates showed a statistically significant correlation with seizure reduction. No independent predictors of long-term outcome of VNS were found. This is the first long-term study using retention rate of VNS to assess effectiveness. VNS is a well-tolerated therapy, but retention rates decline with long follow-up.

PMID:38795656 | DOI:10.1016/j.eplepsyres.2024.107383

Neuromodulation. 2024 May 25:S1094-7159(24)00065-5. doi: 10.1016/j.neurom.2024.03.002. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to conduct a systematic review and meta-analysis assessing the antiinflammatory effects of various VNS methods while exploring multiple antiinflammatory pathways.

MATERIALS AND METHODS: We included clinical trials that used electrical stimulation of the vagus nerve and assessed inflammatory markers up to October 2022. We excluded studies lacking control groups, those with combined interventions, or abstracts without full text. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews. For each inflammatory marker, a random-effects meta-analysis using the inverse variance method was performed. Methods used include transcutaneous auricular VNS (taVNS), transcutaneous cervical VNS (tcVNS), invasive cervical VNS (iVNS), and electroacupuncture VNS (eaVNS). Main reported outcomes included tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, C-reactive protein (CRP), and IL-10. Risk of bias was evaluated using the Cochrane Collaboration Tool (RoB 2.0).

RESULTS: This review included 15 studies, involving 597 patients. No statistically significant general VNS effect was observed on TNF-α, IL-6, and IL-1ß. However, CRP, IL-10, and interferon (IFN)-γ were significantly modulated by VNS across all methods. Subgroup analysis revealed specific stimulation techniques producing significant results, such as taVNS effects in IL-1ß and IL-10, and iVNS in IL-6, whereas tcVNS and eaVNS did not convey significant pooled results individually. Cumulative exposure to VNS, higher risk of bias, study design, and pulse width were identified as effect size predictors in our meta-regression models.

CONCLUSIONS: Pooling all VNS techniques indicated the ability of VNS to modulate inflammatory markers such as CRP, IL-10, and IFN-γ. Individually, methods such as taVNS were effective in modulating IL-1ß and IL-10, whereas iVNS modulated IL-6. However, different VNS techniques should be separately analyzed in larger, homogeneous, and powerful studies to achieve a clearer and more consistent understanding of the effect of each VNS method on the inflammatory system.

PMID:38795094 | DOI:10.1016/j.neurom.2024.03.002

Pharmaceuticals (Basel). 2024 Apr 24;17(5):547. doi: 10.3390/ph17050547.

ABSTRACT

BACKGROUND: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs).

METHODS: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury.

RESULTS: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury.

CONCLUSIONS: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

PMID:38794117 | DOI:10.3390/ph17050547