Insula modulation effects of transcutaneous auricular vagus nerve stimulation treating functional dyspepsia.

This study aimed to develop and validate an atherosclerosis-induced chronic bladder ischemia (CBI) model in female rats and to evaluate mechanosensitive single-unit afferent activity (SAA) in bladder-innervating fibers in both male and female CBI models. Sprague-Dawley rats of both sexes were divided into sham and CBI groups. The CBI group underwent balloon-induced endothelial injury of the iliac arteries and received a 2% cholesterol diet for 8 weeks. Sham rats underwent bilateral inguinal incisions without arterial injury and were fed a regular diet. In female rats, iliac arterial wall thickening, 24-h voiding behavior, cystometric parameters, bladder blood flow, and fibrosis were assessed to evaluate CBI-induced bladder dysfunction. SAAs were recorded under urethane anesthesia. Bladder-innervating fibers were identified via electrical stimulation of the left pelvic nerve and bladder distension. Fibers were classified as Aδ- or C-fibers based on conduction velocity. Female CBI rats showed thickening of the common iliac arteries, increased voiding frequency, shortened intercontraction intervals, reduced bladder blood flow, and detrusor smooth muscle fibrosis, consistent with previous studies in male rats. In both sexes, the CBI group showed significantly higher SAAs in C-fibers than the sham group. No significant differences were found in SAAs of Aδ-fibers, although there was a tendency for female CBI rats to show higher activity. This study successfully established arteriosclerosis-induced CBI accompanied by frequent voiding in female rats, similar to males. In addition, the present findings suggest that C-fiber, but not Aδ-fiber, afferent activity is selectively facilitated under CBI conditions.

Rett syndrome is a neurodevelopmental disorder caused by an X-linked mutation of the MeCP2 gene. Individuals with Rett syndrome, as well as rodent models of this disorder, demonstrate abnormal cortical responses to sound, which impair auditory discrimination ability. Vagus nerve stimulation (VNS) paired with tones has been shown to drive robust changes in the auditory cortex physiology of Mecp2+/- rats and has the potential to improve the communication abilities of individuals with Rett syndrome. The aim of this study was to describe the proteomic differences present in the auditory cortex of the Mecp2+/- rat model of Rett syndrome, as well as the molecular effect of VNS paired with tones. This study used global proteomic analysis of auditory cortex tissue taken from Mecp2+/- rats exposed to VNS paired with tones compared to untreated Mecp2+/- rats and wild-type (WT) littermate controls with no VNS exposure. Our results demonstrate dysregulation of mitochondrial and synaptic proteins in the Mecp2+/- rat auditory cortex. In addition, we show that VNS-tone pairing induces significant alterations to the auditory cortex proteome of Mecp2+/- rats by changing the expression of proteins involved in regulating synaptic vesicles and synaptic transmission. This work provides evidence of key mechanisms that may drive auditory processing dysfunction in Rett syndrome and demonstrates that VNS-tone pairing is sufficient to alter protein expression in the auditory cortex.

Frequent premature atrial complexes (PACs) can increase the risk of atrial fibrillation or atrial tachycardia, and pharmacological therapy can be challenging. To report the use of three-dimensional electro-anatomical mapping of PAC originating from the right atrial free wall and treatment by radiofrequency ablation in three horses. Retrospective case report. Frequent premature atrial complexes (PACs) were diagnosed in three horses. Twelve-lead ECG and vectorcardiography suggested an origin in the right lateral free wall in two horses and the caudal right atrium in one horse. Three-dimensional electro-anatomical mapping (3D EAM) and radiofrequency ablation using the CARTO™ 3 system were performed. Isoprenaline or dobutamine administration allowed activating the focus of PACs during general anaesthesia. Activation mapping using Pattern Matching Filtering identified the origin of PACs at the mid portion of the right atrial free wall in all horses. In the first horse, ablation was not performed due to pacing-induced phrenic nerve stimulation at the site of earliest activation. In the second horse, PACs disappeared after the 18th energy application and were no longer inducible by dobutamine. In the last horse, ablation was not successful in eliminating PACs. Small number of cases. The 3D EAM identified the focus of PACs at the right atrial free wall in three horses, revealing it as a possible arrhythmogenic area. Although still challenging, radiofrequency ablation has promise as a treatment to provide a permanent solution for frequent PACs.

Vagus nerve stimulation (VNS) is a neuromodulatory intervention with antiinflammatory and autonomic regulatory properties. Although its clinical applications have primarily been explored in neurological disorders, its potential role in pulmonary and respiratory outcomes across preclinical and clinical settings remains incompletely characterized and dispersed across different study domains. This scoping review aimed to map the available evidence on the effects of VNS on the pulmonary and respiratory systems, with particular emphasis on inflammatory and autonomic mechanisms. This scoping review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Three reviewers systematically searched PubMed, Web of Science, and the Cochrane Library for studies published between January 2020 and February 2026. Original preclinical and clinical studies investigating invasive or noninvasive VNS and reporting pulmonary, respiratory physiology, autonomic, or inflammatory outcomes were included. A total of 159 records were identified, of which 12 studies met the inclusion criteria. The evidence base was predominantly preclinical. In animal studies, invasive cervical VNS was frequently associated with reductions in pulmonary inflammation, histopathological lung injury, and proinflammatory cytokine expression. Clinical studies were limited and heterogeneous, but generally indicated variable modulation of autonomic function, including changes in parasympathetic activity, as well as heterogeneous effects on systemic inflammatory markers and limited respiratory outcomes. Current evidence suggests that VNS may modulate pulmonary inflammatory responses in preclinical models. However, clinical evidence remains limited and heterogeneous, particularly regarding autonomic and respiratory outcomes. Well-designed clinical trials using standardized stimulation protocols and predefined respiratory end points are needed to clarify its therapeutic potential in respiratory disorders.

Neuromodulation and sudden unexpected death in epilepsy: A systematic review of SUDEP rates across VNS, DBS, and RNS therapies.

The stress-myopia pathway: A pivotal hub in myopia pathogenesis.

Juvenile myasthenia gravis (JMG) is a rare autoimmune disease acquired in childhood, comprising 8%-15% of all myasthenia gravis cases depending on geographic and ethnic populations. Ocular myasthenia gravis presents as ptosis with extraocular movement restriction and is frequently misdiagnosed as third nerve palsy or congenital ptosis when bilateral. Early diagnosis prevents disease progression and unnecessary interventions. We report a case of JMG initially misdiagnosed as Guillain-Barré syndrome (GBS) to highlight diagnostic pitfalls. A 4-year-old girl presented with left eye ptosis, followed by bilateral ptosis after 2 days, then gait disorder and inability to stand after 5 days. She had a previous admission 2 months earlier with severe respiratory distress, for which she received intravenous immunoglobulin (IVIG) under the suspicion of GBS. In the current admission, bilateral ptosis was evident, and repetitive nerve stimulation (RNS) showed a decremental response of > 10%, consistent with myasthenia gravis. Anti-acetylcholine receptor (AChR) antibody was positive. She was treated with pyridostigmine (5 mg/kg/day) and showed good response. JMG should be considered in the differential diagnosis of acute muscle weakness with cranial nerve involvement, even when respiratory failure dominates, and normal cerebrospinal fluid protein in suspected GBS should prompt re-evaluation.

We investigated the impact of an 8-week tailored balance program, with or without superimposed sensory stimulation (local vibration [LV], and/or transcutaneous electrical nerve stimulation [TENS]), on balance and walking performance in older adults. Seventy-five healthy elderly participants (age 79.9 ± 3.9 years) were randomly assigned to one of four groups: postural exercises only ( n = 17), exercises with LV ( n = 19), exercises with TENS ( n = 19), and exercises with LV+TENS ( n = 20). For LV, TENS, and LV+TENS groups, proprioceptive stimulation targeted the triceps surae and tibialis anterior. Participants completed a baseline assessment including the Berg Balance Scale, Short Physical Performance Battery, 6-min walk test, 10-meter walk test, and Timed Up and Go test. A similar assessment was performed 8 weeks later, and after the 8-week tailored intervention, which consisted of two 1-h sessions per week. Balance and walking capacities were finally reassessed 8 weeks after training. In all groups, reliability of the outcome measures was moderate to high between baseline and preintervention values (intraclass correlation coefficients >0.63). Postintervention, linear mixed-effects models revealed significant improvements in Berg Balance Scale and Short Physical Performance Battery scores (53.1 ± 2.4 and 10.9 ± 0.9 vs 54.9 ± 2.4 and 11.5 ± 0.9, P < 0.001), and reduced times for Timed Up and Go test (7.3 ± 1.7 s vs 6.6 ± 1.7 s, P < 0.001) and increased 10-meter walk test velocity (3.6 ± 0.7 m/sec vs 3.4 ± 0.7 m/sec, P = 0.004), with no group differences nor interactions. Benefits were partially maintained 8 weeks after training. The interventions did not affect 6-min walk test performance (525.5 ± 75.1 m vs 527.8 ± 74.1 m, P = 0.143). Tailored balance exercises alone significantly enhanced postural control and walking capacity in healthy older adults. Additional sensory stimulation provided no extra benefit, suggesting that for healthy older adults without major balance impairments, exercises alone may suffice to achieve meaningful functional improvements.

Neuromuscular junction (NMJ) disorders such as myasthenia gravis, Lambert-Eaton myasthenic syndrome, and botulism are characterized by impaired synaptic transmission leading to weakness. This review examines the electrodiagnostic evaluation of these conditions, emphasizing the importance of techniques such as repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG) for confirming the diagnosis and distinguishing presynaptic from postsynaptic defects. The reduced safety factor of neuromuscular transmission (NMT) in postsynaptic disorders produces a decrement in compound muscle action potential (CMAP) amplitude and area with low-frequency stimulation, whereas presynaptic disorders show small baseline CMAPs that increase markedly in amplitude and area (postactivation facilitation) after brief exercise or during high-frequency stimulation. SFEMG, the most sensitive test of abnormal NMT, measures neuromuscular jitter-temporal variability in action potential generation-and also reflects a compromised safety factor. Fiber density remains normal in primary NMJ disorders, distinguishing them from conditions with neuropathic reinnervation, such as motor neuron disease. Proper performance and interpretation of these electrodiagnostic studies are essential for accurate diagnosis, assessment of disease severity, and guiding management of NMJ disorders.

Neuromodulation through transcutaneous electrical nerve stimulation in knee osteoarthritis: A systematic review and meta-analysis of pain, function, and its role in multimodal rehabilitation.

Vascular cognitive impairment (VCI) is a prevalent and heterogeneous condition, both clinically and pathophysiologically, that still lacks approved treatment. Peripheral electrical nerve stimulation (PENS) shows promise for VCI management, yet its underlying neurobiological mechanisms are not well understood. VCI was induced in rats via permanent bilateral common carotid artery occlusion. Cognitive function was assessed using the Morris water maze, Y-maze, and novel object recognition. Synaptic plasticity was evaluated through long-term potentiation recordings and Golgi staining. The nucleus tractus solitarius (NTS)-medial septum-hippocampus circuit was dissected using fiber photometry recording, immunofluorescence multiplex labeling, in vivo multichannel recordings, anterograde/retrograde tracing, and chemogenetic manipulation. We found that PENS at Zusanli (ST36) acupoint significantly elevated hippocampal acetylcholine levels, enhanced synaptic plasticity, and rescued spatial and nonspatial memory deficits in VCI rats. Chemogenetic activation of cholinergic neurons in the NTS enhanced the cognitive function of VCI rats, whereas chemogenetic inhibition of these neurons counteracted the cognitive benefits of PENS. The NTS sends cholinergic projections to the hippocampal cornu ammonis 1 region through the medial septum. Specific inhibition of NTSChAT-medial septumChAT-cornu ammonis 1 circuit reversed the enhancement of spatial memory observed in VCI rats treated with PENS, while leaving the nonspatial memory unaffected. Our findings identify the NTS-medial septum-cornu ammonis 1 cholinergic circuit as a critical mechanism mediating PENS-induced reversal of spatial memory deficits in VCI, revealing a novel and spatially selective therapeutic target for VCI.

Repetitive peripheral magnetic stimulation (rPMS) can improve motor dysfunction and spasticity in individuals with central nervous system lesions. However, its underlying neural mechanisms remain poorly understood. This study investigated the effects of 15-min rPMS applied to the wrist extensor muscles on reciprocal inhibition between the wrist flexor and extensor muscles in healthy adults. First, to assess distinct inhibitory mechanisms, the effects of rPMS on reciprocal inhibition directed from extensor carpi radialis (ECR) to the flexor carpi radialis (FCR) were examined using the FCR H-reflex conditioned by radial nerve stimulation by assessing disynaptic Ia inhibition and D1 inhibition at conditioning-test intervals of -0.3 ± 0.2 ms and 13 ms, respectively. At an intensity sufficient to elicit muscle contraction, rPMS significantly enhanced disynaptic Ia inhibition, but had no significant effect on D1 inhibition. Next, we assessed the effects of rPMS on disynaptic Ia inhibition and D1 inhibition directed in the opposite direction from FCR to ECR. In this case, rPMS significantly reduced disynaptic Ia inhibition but had no significant effect on D1 inhibition. Furthermore, rPMS did not alter the excitability of monosynaptic reflex pathways in the stimulated ECR or its antagonist FCR. Taken together, these findings indicate that rPMS applied to the wrist extensor muscles enhances disynaptic Ia inhibition from the stimulated muscles to their antagonist motoneurons and attenuates disynaptic Ia inhibition in the opposite direction, suggesting that rPMS modulates disynaptic Ia inhibition in a direction-dependent manner.NEW & NOTEWORTHY Repetitive peripheral magnetic stimulation (rPMS) is a promising therapeutic tool for motor recovery, yet the underlying mechanisms remain unclear. We demonstrated rPMS applied to the wrist extensors induces direction-dependent modulation of spinal reciprocal inhibition, selectively enhancing disynaptic Ia inhibition toward the antagonist while attenuating it in the opposite direction. These results provide novel evidence that rPMS can modulate specific spinal inhibitory interactions and provide a physiological basis for developing targeted neuromodulation protocols to promote motor recovery.

The study aimed to investigate whether a 5-week sprint interval training (SIT) could improve neuromuscular function (NMF), alter electromyographic activity (EMG), and attenuate fatigability, ultimately resulting in improved cycling performance during constant work rate (CWR) exercise within the severe-intensity domain. Twenty-one recreational active males were randomly assigned into a SIT group (SITG; n=11) that underwent 5weeks of SIT (4-6, 30-s Wingate bouts) and a control group (CON; n=10). The study was conducted in a parallelindependent group study. At the pre- and post-training periods, participants performed (i) a ramp incremental test; (ii) CWR exercise at 150% of the pre- and post-training power output at the respiratory compensation point (RCP-PO) until task failure, with the NMF assessed at baseline (NMFBL) and immediately after exercise [isometric maximal voluntary contraction+peripheral nerve stimulations with measurement of the force and EMG]. Pre- and post-training NMFBL was used to assess isometric performance, whereas the difference between NMFBL and NMF after exercise was used to assess performance fatigability. Furthermore, EMG was also measured during exercise. SITG showed a significant increase in absolute RCP-PO compared to CON (+11.0% vs. -0.7%, respectively; p<0.01), performing the post-training CWR at a greater power output than in pre-training. Despite this, no significative differences were observed for the NMFBL, fatigability, and EMG during CWR exercise. These findings suggest that SIT may improve EMG activity efficiency (i.e.,requiring the same level of activation to sustain a greater absolute power output) during CWR exercise within the severe-intensity domain. However, NMFBL, fatigability, and time-to-task failure performance remained unchanged.

The diagnosis of chronic low back pain is frequently complicated by the absence of identifiable pathoanatomical causes on imaging. Consequently, clinical guidelines often advocate for interventional diagnostic procedures, such as medial branch nerve blocks, for suspected facet joint syndrome. Despite their utility, these interventions involve significant resource costs and potential risks associated with needle gauges and pharmacological agents. This study describes a protocol to evaluate percutaneous electrical nerve stimulation (PENS) as a safer, drug-free, and more cost-effective alternative. A parallel and multicenter study with an experimental design through a randomized clinical trial will be conducted. Adults with chronic low back pain and facet-mediated pain confirmed by two positive comparative medial branch diagnostic blocks will be randomized into four parallel groups: PENS, diagnostic medial branch nerve block (with local anesthetic), PENS + nerve block, and PENS + placebo block (full block ritual without active perineural anesthetic). The primary outcomes will be analgesic response. Secondary outcomes include pressure pain threshold, disability, health-related quality of life, rescue analgesic consumption, and the incidence/severity of local and systemic adverse events.Clinical Trial Registration: The www.clinicaltrials.gov identifier is NCT07273006.

To integrate mechanistic and clinical evidence on vagal regulation of immunity via the cholinergic anti-inflammatory pathway, linking neural and inflammatory signaling in rheumatoid arthritis (RA). It highlights how reduced vagal tone contributes to disease onset and progression and frames neuromodulation as a rationale for adjunctive therapeutic strategies. Preclinical and clinical data demonstrate that vagal efferent activity modulates immune responses through noradrenergic circuits and activation of α7-nicotinic-acetylcholine-receptors on immune cells, inhibiting NF-κB nuclear translocation and reducing pro-inflammatory cytokines. This neuroimmune axis interacts with the hypothalamic-pituitary-adrenal axis and the microbiome, supporting an integrated model of inflammation. Vagus nerve stimulation (VNS) has been associated with reductions in inflammatory markers and clinically meaningful improvements in patients with RA. Implantable VNS has demonstrated efficacy and has received regulatory approval for moderate-to-severe RA refractory to disease-modifying antirheumatic drugs; however, the available evidence remains limited and requires confirmation in larger and more diverse populations. Noninvasive approaches show favorable safety profiles but heterogeneous efficacy and currently lack regulatory approval for immune-mediated diseases. VNS represents a promising adjunct to conventional immunosuppressive therapy for RA. Further well-designed trials are needed to standardize stimulation protocols, and define optimal strategies for clinical implementation.

Acupuncture-like transcutaneous electrical nerve stimulation for patients with irritable bowel syndrome: Pilot mixed-methods study.

Shoulder pain during daily activities is a common musculoskeletal complaint affecting individuals across all age groups. Among its causes, Shoulder Impingement Syndrome (SIS) is one of the most prevalent. This study aimed to compare the effects of Visceral Manipulation (VM) and Integrated Neuromuscular Inhibition Technique (INIT) on pain intensity, shoulder function, and range of motion (ROM) in patients with upper trapezius trigger points associated with SIS, while considering the proposed role of VM in modulating musculoskeletal conditions through viscerosomatic interactions. This randomized controlled trial included (n=75) patients aged 20-40years with SIS and trigger points in the superior trapezius region were recruited. Participants were randomly assigned to three groups. Group A (n=25) received VM combined with traditional physical therapy modalities, including Transcutaneous Electrical Nerve Stimulation (TENS), hot pack application, ultrasound therapy, and therapeutic exercises. Group B (n=25) received INIT in addition to the same traditional physical therapy regimen. Group C (n=25), the control group, received only traditional physical therapy. Interventions were delivered over a 4-week period, and all outcomes were reassessed immediately following completion of the intervention. All participants were assessed using the Visual Analog Scale (VAS), pressure algometer, standard goniometer, and the Shoulder Pain and Disability Index (SPADI). Post-treatment analysis revealed statistically significant improvements across all groups in pain intensity, shoulder flexion and abduction range of motion (ROM), and functional level (SPADI) (p<0.001). Group A (VM) and Group B (INIT) showed greater reductions in VAS scores (MD=3.96 and 4.00, respectively; p=0.001), increases in pressure pain threshold (PPT) (MD=6.88 and 7.34 lb; p=0.001), and improvements in shoulder abduction (MD=98.40° and 99.68°; p=0.001) and flexion ROM (MD=103.48° and 103.16°; p=0.001) compared to Group C. SPADI scores decreased significantly in Groups A and B (MD=27.24 and 23.40; p=0.001), indicating enhanced functional recovery. Between-group comparisons confirmed that Groups A and B were significantly superior to Group C (p<0.01), with no significant difference between Groups A and B (p>0.05). These findings should be interpreted cautiously, as the exploratory nature of the comparison and the limited evidence base supporting VM preclude definitive conclusions regarding its conceptual or mechanistic superiority compared to standard physiotherapy alone in managing pain, improving shoulder function, and increasing ROM in patients with upper trapezius trigger points associated with SIS. CkinicaTrials.gov (https://clinicaltrials.gov/study/NCT06271720).

Erectile dysfunction (ED) secondary to cavernous nerve injury (CNI), such as that occurring after radical prostatectomy, remains a significant clinical challenge, particularly among patients who do not respond to phosphodiesterase Type 5 inhibitors (PDE5i). Extracellular vesicles (EVs) derived from umbilical cord blood (UCB) have recently emerged as a promising cell-free therapeutic modality owing to their potent regenerative and anti-inflammatory properties. This study aimed to investigate the therapeutic efficacy of UCB-derived EVs (UCB-EVs) in restoring erectile function in a bilateral CNI mouse model. UCB-EVs were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Their neuroregenerative effects were assessed in vitro using Neuro-2a (N2a) cell migration assays and ex vivo by evaluating neurite outgrowth in major pelvic ganglia (MPG) and dorsal root ganglia (DRG). In vivo, fluorescently labeled UCB-EVs were tracked following intracavernous administration, and erectile function was quantified using maximal ΔICP and baseline-corrected total ΔICP during cavernous nerve stimulation. Histological and biochemical analyses were conducted to assess neurovascular integrity, apoptosis, proliferation, oxidative stress, and activation of PI3K/AKT signaling in penile tissues. UCB-EVs significantly enhanced N2a cell migration in vitro and promoted neurite sprouting in MPG and DRG explants ex vivo. In CNI mice, intracavernous administration of UCB-EVs resulted in dose-dependent recovery of erectile function, as demonstrated by significant increases in maximal ΔICP and baseline-corrected total ΔICP during cavernous nerve stimulation. Biodistribution analysis demonstrated preferential localization of UCB-EVs to the penile neurovascular bundle. Histological and molecular evaluations revealed preservation of endothelial and neuronal populations, suppression of apoptosis, enhanced cellular proliferation, attenuation of reactive oxygen species (ROS) accumulation, and activation of PI3K/AKT signaling pathways in UCB-EV-treated mice. UCB-EVs promote neurovascular regeneration, mitigate oxidative stress, and improve erectile function following CNI. These findings suggest that UCB-EVs represent a promising regenerative strategy for postprostatectomy ED, particularly in patients refractory to conventional pharmacotherapy.

Sex-specific effects of chronic electrical acustimulation and sacral nerve stimulation in a rodent model of irritable bowel syndrome.