Nat Commun. 2024 Nov 13;15(1):9824. doi: 10.1038/s41467-024-54056-w.

ABSTRACT

Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS-LPB-PVT-PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS-LPB-PVT-PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain.

PMID:39537596 | PMC:PMC11561356 | DOI:10.1038/s41467-024-54056-w

Epilepsy Behav. 2024 Nov 12;161:110138. doi: 10.1016/j.yebeh.2024.110138. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effects of vagus nerve stimulation (VNS) on the seizure frequency in patients with drug-resistant epilepsy (DRE) and bilateral temporal lobe epilepsy (bi-TLE). Additionally, we aimed to determine the safety of VNS and its side effects.

METHODS: Our retrospective study included 17 patients with bi-TLE who underwent VNS-device implantation at our center from 1997 to 2019. The main outcome was a reduction in seizure frequency. Bitemporal cases were confirmed using scalp electroencephalography (EEG) or invasive electroencephalography (iEEG).

RESULTS: The median age at seizure onset was 18 years. Bi-TLE was confirmed by scalp EEG in 47 % and by iEEG in 53 % of the patients. The median follow-up period was 36 months. The median seizure frequency per month before and after VNS was 9.5 (IQR = 4.3-35.3) and 2 (IQR = 0.8-4.2), respectively. Compared to baseline, 70.5 % of the patients achieved ≥ 50 % reduction in seizure frequency, whereas 35.3 % experienced either no or minimal reduction in seizure frequency. The response rate (>50 % reduction in seizure frequency) was 87.5 % in patients who underwent scalp EEG and 55.5 % in those who underwent iEEG. For VNS treatment, the median follow-up was at 36 months (IQR = 17-46.5). Adverse effects were observed in 59 % of the patients, including cough and hoarseness.

DISCUSSION: Therapeutic choices are limited in cases of drug-resistant bi-TLE. Our study on VNS-device implantation in bi-TLE suggests a positive outcome.

PMID:39536365 | DOI:10.1016/j.yebeh.2024.110138

Innovation (Camb). 2024 Oct 21;5(6):100721. doi: 10.1016/j.xinn.2024.100721. eCollection 2024 Nov 4.

ABSTRACT

Cough is a vital defensive reflex for expelling harmful substances from the airway. The sensory afferents for the cough reflex have been intensively studied. However, the brain mechanisms underlying the cough reflex remain poorly understood. Here, we developed a paradigm to quantitatively measure cough-like reflexes in mice. Using this paradigm, we found that prodynorphin-expressing (Pdyn+) neurons in the nucleus of the solitary tract (NTS) are critical for capsaicin-induced cough-like reflexes. These neurons receive cough-related neural signals from Trpv1+ vagal sensory neurons. The activation of Pdyn+ NTS neurons triggered respiratory responses resembling cough-like reflexes. Among the divergent projections of Pdyn+ NTS neurons, a glutamatergic pathway projecting to the caudal ventral respiratory group (cVRG), the canonical cough center, was necessary and sufficient for capsaicin-induced cough-like reflexes. These results reveal that Pdyn+ NTS neurons, as a key neuronal population at the entry point of the vagus nerve to the brainstem, initiate cough-like reflexes in mice.

PMID:39529953 | PMC:PMC11551472 | DOI:10.1016/j.xinn.2024.100721

Ann Surg Oncol. 2024 Nov 11. doi: 10.1245/s10434-024-16426-y. Online ahead of print.

ABSTRACT

BACKGROUND: Leiomyomas are benign smooth muscle tumors found at the gastroesophageal junction (GEJ) ( Mathew G, Osueni A, Carter YM. Esophageal Leiomyoma. StatPearls. StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC; 2024.). Traditional management often involves total gastrectomy with esophagojejunostomy, a highly morbid procedure that impacts quality of life ( Teh JL, Shabbir A. Resection of Gastroesophageal Junction Submucosal Tumors (SMTs). In: Lomanto D, Chen WT-L, Fuentes MB (eds). Mastering Endo-Laparoscopic and Thoracoscopic Surgery: ELSA Manual. Springer Nature Singapore; 2023. pp. 207-211.). We present a case of a large endophytic GEJ leiomyoma managed with robotic-assisted endoluminal mass resection and transoral specimen extraction.

METHODS: A 46-year-old female with upper abdominal pain was diagnosed with a 9×3 cm lobular leiomyoma at the GEJ via computed tomography and endoscopic biopsy. The tumor was excised using the da Vinci Xi system, with transgastric endoluminal trocar placement. The GEJ defect was closed over a gastroscope, allowing visualization and continuous insufflation.

RESULTS: Complete resection was achieved without creating a full-thickness defect. The mass was retrieved transorally with an endoscope, and the defect was repaired to minimize the risk of stenosis. The procedure lasted 236 min with minimal blood loss (150 mL) and with no complications. Pathology confirmed leiomyoma with negative margins. The patient was discharged on postoperative day 4 on a full liquid diet, requiring no narcotics, and was later advanced to a regular diet. No complications, readmissions, or mortality were reported at the 7-month follow-up.

CONCLUSIONS: Robotic-assisted endoluminal GEJ mass resection is a feasible, safe technique for large benign tumors, preserving the stomach and GEJ, and thereby obviating lifestyle changes from total gastrectomy. It minimizes the risk of anastomotic leak, stricture, vagus nerve injury, gastroparesis, and reflux (Levine et al. AJR Am J Roentgenol. 157:1189-1194). Closure of the GEJ defect using an endoscope allows for adequate insufflation of the proximal stomach. When feasible, combining transoral specimen extraction enhances the benefits of this minimally invasive approach (Yin et al. Chin Clin Oncol. 13:6).

PMID:39527157 | DOI:10.1245/s10434-024-16426-y

Hepatobiliary Surg Nutr. 2024 Oct 1;13(5):891-893. doi: 10.21037/hbsn-24-516. Epub 2024 Sep 26.

NO ABSTRACT

PMID:39507731 | PMC:PMC11534763 | DOI:10.21037/hbsn-24-516

Front Aging Neurosci. 2024 Oct 23;16:1444703. doi: 10.3389/fnagi.2024.1444703. eCollection 2024.

ABSTRACT

BACKGROUND: Previous studies have evaluated the safety and efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of Parkinson’s disease (PD). However, the mechanism underlying the effect of taVNS on PD remains to be elucidated. This study aimed to investigate the immediate effects of taVNS in PD patients.

METHODS: This crossover self-controlled study included 50 PD patients. Each patient underwent three sessions of resting-state functional magnetic resonance imaging (rs-fMRI) under three conditions: real taVNS, sham taVNS, and no taVNS intervention. We analyzed whole-brain amplitude of low-frequency fluctuations (ALFF) from preprocessed fMRI data across different intervention conditions. ALFF values in altered brain regions were correlated with clinical symptoms in PD patients.

RESULTS: Forty-seven participants completed the study and were included in the final analysis. Real taVNS was associated with a widespread decrease in ALFF in the right hemisphere, including the superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus (voxel p < 0.001, GRF corrected). The ALFF value in the right superior parietal lobule during real taVNS was negatively correlated with the Unified Parkinson’s Disease Rating Scale Part III (r = -0.417, p = 0.004, Bonferroni corrected).

CONCLUSION: TaVNS could immediately modulate the functional activity of brain regions involved in superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus. These findings offer preliminary insights into the mechanism of taVNS in treating PD and bolster confidence in its long-term therapeutic potential. TaVNS appears to reduce ALFF values in specific brain regions, suggesting a potential modulation mechanism for treating PD.

PMID:39507202 | PMC:PMC11537911 | DOI:10.3389/fnagi.2024.1444703

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2024 Oct;46(5):776-782. doi: 10.3881/j.issn.1000-503X.15872.

ABSTRACT

The joints have abundant sensory nerves and sympathetic nerve fibers,which convert physical and chemical stimuli in the joints into nerve impulses that are transmitted to the central nervous system and participate in the hypersensitivity reactions of inflammatory joint diseases such as osteoarthritis (OA).This paper summarizes the distribution and functional characteristics of intra-articular nerves and focuses on the mechanism of the vagus-sympathetic autonomic circuit in regulating the immune microenvironment in joints in the case of OA.In addition,intra-articular inflammatory cytokines represented by tumor necrosis factor-α and interleukin-6 directly or indirectly induce sensory nerve action potential and activate the pain transduction pathway from the local joint to the central nervous system.The sensory nerves in the joints in the case of OA are also involved in the recruitment of immune cells and inflammatory cytokines.This neuro-immune interaction model not only provides a variety of new targets for the treatment of OA but also suggests that the treatment of OA should adopt a holistic view with comprehensive consideration of the nerve and immune microenvironment in the bone and joint and their mutual influences.

PMID:39502061 | DOI:10.3881/j.issn.1000-503X.15872

Anaesth Rep. 2024 Nov 4;12(2):e12332. doi: 10.1002/anr3.12332. eCollection 2024 Jul-Dec.

ABSTRACT

A 67-year-old woman with no history of cardiovascular disease, undergoing an elective laparoscopic cholecystectomy, experienced severe bradycardia and cardiac arrest immediately following an alveolar recruitment manoeuvre under general anaesthesia. Prompt cardiopulmonary resuscitation restored cardiac output within 2-3 min. Postoperatively, she remained stable and was discharged following 24 h of monitoring. The cardiac arrest was likely triggered by vagal nerve stimulation and activation of intrinsic cardiac reflexes by the alveolar recruitment manoeuvre. The event emphasises a rare, but significant, risk of the routine management of pulmonary atelectasis.

PMID:39498314 | PMC:PMC11532626 | DOI:10.1002/anr3.12332

Cureus. 2024 Oct 1;16(10):e70613. doi: 10.7759/cureus.70613. eCollection 2024 Oct.

ABSTRACT

The international healthcare community has encountered several difficulties because of the COVID-19 pandemic brought on by SARS-CoV-2. COVID-19 can lead to an abnormal immune response that features excessive inflammation, so targeting the vagus nerve through non-invasive vagus nerve stimulation (nVNS) may hold promise as an intervention. This meta-analysis aimed to examine the outcomes of using nVNS on different inflammatory biomarkers in COVID-19 patients. Up until May 2023, we performed a review of online databases. We included randomized controlled trials (RCTs) that discussed how nVNS affected patients with COVID-19’s clinical outcomes. Using the Revman 5.4 software (Cochrane, London, United Kingdom), a meta-analysis was carried out to find the pooled mean difference (MD), with 95% confidence intervals (CIs), of nVNS effects on different inflammatory biomarkers, including interleukin-10 (IL-10), C-reactive protein (CRP), IL-6, and cortisol levels. The review included four RCTs involving 180 COVID-19 patients. Following nVNS treatment, there was a significant increase in IL-10 levels (MD = 1.53, 95% CI: 0.77, 2.29; p < 0.001). CRP levels (MD = -2.24, 95% CI: -4.52, 0.05; p = 0.06), IL-6 levels (MD = 4.07, 95% CI: -3.16, 11.32; p = 0.27), cortisol levels (MD = 1.45, 95% CI: -11.67, 14.57; p = 0.83), and D-dimer levels (MD = -0.47, 95% CI: -1.31, 0.38; p = 0.28) did not differ significantly. These findings suggest that nVNS may positively impact certain inflammatory markers in COVID-19 patients, suggesting that nVNS could be a beneficial adjunctive treatment.

PMID:39493183 | PMC:PMC11528624 | DOI:10.7759/cureus.70613

Brain Topogr. 2024 Nov 2;38(1):11. doi: 10.1007/s10548-024-01088-6.

ABSTRACT

Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive form of electrical brain stimulation, has shown potent therapeutic potential for a wide spectrum of conditions. How taVNS influences the characterization of motion sickness – a long mysterious syndrome with a polysymptomatic onset – remains unclear. Here, to examine taVNS-induced effects on brain function in response to motion-induced nausea, 64-channel electroencephalography (EEG) recordings from 42 healthy participants were analyzed; collected during nauseogenic visual stimulation concurrent with taVNS administration, in a crossover randomized sham-controlled study. Cortical neuronal generators were estimated from the obtained EEG using exact low-resolution brain electromagnetic tomography (eLORETA). While both sham and taVNS increased insula activation during electrical stimulation, compared to baseline, taVNS additionally augmented middle frontal gyrus neuronal activity. Following taVNS, brain regions including the supramarginal, parahippocampal, and precentral gyri were activated. Contrasting sham, taVNS markedly increased activity in the middle occipital gyrus during stimulation. A repeated-measures ANOVA showed that taVNS reduced motion sickness symptoms. This reduction in symptoms correlated with taVNS-induced neural activation. Our findings provide new insights into taVNS-induced brain changes, during and after nauseogenic stimuli exposure, including accompanying behavioral response. Together, these findings suggest that taVNS has promise as an effective neurostimulation tool for motion sickness management.

PMID:39487878 | DOI:10.1007/s10548-024-01088-6