Search

Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To explore the effects of tactile stimulation using air pressure at the auricular branch of the vagus nerve on autonomic activity in healthy individuals. Methods Three types of tactile stimulation were used in this study: continuous low-amplitude, continuous high-amplitude, and pulsed airflow. The tactile stimulations were provided to the cymba concha to investigate autonomic activity in 22 healthy participants. The mean heart rate (HR) and parameters of HR variability, including the standard deviation of R-R intervals (SDNN) and root mean square of successive R-R interval differences (RMSSD) were compared at baseline, stimulation, and recovery periods. Results Two-way repeated measures ANOVA indicated a significant main effect of time on HR (p=0.001), SDNN (p=0.003), and RMSSD (p

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are incurable autoimmune diseases characterized by chronic inflammation of the gastrointestinal tract. There is increasing evidence that inappropriate interaction between the enteric nervous system and central nervous system and/or low activity of the vagus nerve, which connects the enteric and central nervous systems, could play a crucial role in their pathogenesis. Therefore, it has been suggested that appropriate neuroprosthetic stimulation of the vagus nerve could lead to the modulation of the inflammation of the gastrointestinal tract and consequent long-term control of these autoimmune diseases. In the present paper, we provide a comprehensive overview of (1) the cellular and molecular bases of the immune system, (2) the way central and enteric nervous systems interact and contribute to the immune responses, (3) the pathogenesis of the inflammatory bowel disease, and (4) the therapeutic use of vagus nerve stimulation, and in particular, the transcutaneous stimulation of the auricular branch of the vagus nerve. Then, we expose the working hypotheses for the modulation of the molecular processes that are responsible for intestinal inflammation in autoimmune diseases and the way we could develop personalized neuroprosthetic therapeutic devices and procedures in favor of the patients. [ABSTRACT FROM AUTHOR]

Auricular vagus nerve stimulation (aVNS) is a novel neuromodulatory therapy used for treatment of various chronic systemic disorders. Currently, aVNS is non-individualized, disregarding the physiological state of the patient and therefore making it difficult to reach optimum therapeutic outcomes. A closed-loop aVNS system is required to avoid over-stimulation and under-stimulation of patients, leading to personalized and thus improved therapy. This can be achieved by continuous monitoring of individual physiological parameters that serve as a basis for the selection of optimal aVNS settings. In this work we developed a novel aVNS hardware for closed-loop application, which utilizes cardiorespiratory sensing using embedded sensors (and/or external sensors), processes and analyzes the acquired data in real-time, and directly governs settings of aVNS. We show in-lab that aVNS stimulation can be arbitrarily synchronized with respiratory and cardiac phases (as derived from respiration belt, electrocardiography and/or photo plethysmography) while mimicking baroreceptor-related afferent input along the vagus nerve projecting into the brain. Our designed system identified > 90% of all respiratory and cardiac cycles and activated stimulation at the target point with a precision of ± 100 ms despite the intrinsic respiratory and heart rate variability reducing the predictability. The developed system offers a solid basis for future clinical research into closed-loop aVNS in favour of personalized therapy. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are incurable autoimmune diseases characterized by chronic inflammation of the gastrointestinal tract. There is increasing evidence that inappropriate interaction between the enteric nervous system and central nervous system and/or low activity of the vagus nerve, which connects the enteric and central nervous systems, could play a crucial role in their pathogenesis. Therefore, it has been suggested that appropriate neuroprosthetic stimulation of the vagus nerve could lead to the modulation of the inflammation of the gastrointestinal tract and consequent long-term control of these autoimmune diseases. In the present paper, we provide a comprehensive overview of (1) the cellular and molecular bases of the immune system, (2) the way central and enteric nervous systems interact and contribute to the immune responses, (3) the pathogenesis of the inflammatory bowel disease, and (4) the therapeutic use of vagus nerve stimulation, and in particular, the transcutaneous stimulation of the auricular branch of the vagus nerve. Then, we expose the working hypotheses for the modulation of the molecular processes that are responsible for intestinal inflammation in autoimmune diseases and the way we could develop personalized neuroprosthetic therapeutic devices and procedures in favor of the patients.

Abstract Background Rheumatoid arthritis (RA) is a chronic and debilitating inflammatory disease characterized by extensive joint tissue inflammation. Implantable bioelectronic devices targeting the inflammatory reflex reduce TNF production and inflammation in preclinical models of inflammatory disease, and in patients with RA and Crohn’s disease. Here, we assessed the effect of applying a vibrotactile device to the cymba concha of the external ear on inflammatory responses in healthy subjects, as well as its effect on disease activity in RA patients. Methods Six healthy subjects received vibrotactile treatment at the cymba concha, and TNF production was analyzed at different time points post-stimulation. In a separate study, nineteen healthy subjects were enrolled in a randomized cross-over study, and effects of vibrotactile treatment at either the cymba concha or gastrocnemius on cytokine levels were assessed. In addition, the clinical efficacy of vibrotactile treatment on disease activity in RA was assessed in nine patients with RA in a prospective interventional study. Results Vibrotactile treatment at the cymba concha reduced TNF levels, and the suppressive effect persisted up to 24 h. In the cross-over study with 19 healthy subjects, vibrotactile treatment at the cymba concha but not at the gastrocnemius significantly reduced TNF, IL-1β, and IL-6 levels compared to pre-treatment baseline (TNF p

Background: Migraine is a common disabling primary headache condition. Although strives have been made in treatment, there remains an unmet need for safe, effective acute, and preventative treatments. The promising concept of neuromodulation of relevant neuronal targets in a noninvasive fashion for the treatment of primary headache disorders has led to the trial of numerous devices over the years.Objective: We aimed to review the evidence on current neuromodulation treatments available for the management of primary headache disorders.Methods: Randomized controlled trial as well as open-label and real-world studies on central and peripheral cephalic and noncephalic neuromodulation modalities in primary headaches were critically reviewed.Results: The current evidence suggests a role of single-pulse transcranial magnetic stimulation, supraorbital nerve stimulation, and remote noncephalic electrical stimulation as migraine abortive treatments, with stronger evidence in episodic rather than in chronic migraine. Single-pulse transcranial magnetic stimulation and supraorbital nerve stimulation also hold promising evidence in episodic migraine prevention and initial positive evidence in chronic migraine prevention. More evidence should clarify the therapeutic role of the external vagus nerve stimulation and transcranial direct current stimulation in migraine. However, external vagus nerve stimulation may be effective in the acute treatment of episodic but not chronic cluster headache, in the prevention of hemicrania continua and paroxysmal hemicrania but not of short-lasting neuralgiform headache attacks. The difficulty in setting up sham-controlled studies has thus far prevented the publication of robust trials. This limitation along with the cost of these therapies has meant that their use is limited in most countries.Conclusion: Neuromodulation is a promising nonpharmacological treatment approach for primary headaches. More studies with appropriate blinding strategies and reduction of device cost may allow more widespread approval of these treatments and in turn increase clinician's experience in neuromodulation. [ABSTRACT FROM AUTHOR]

Therapeutic applications of auricular vagus nerve stimulation (VNS) have drawn recent attention. Since the targeted stimulation process and parameters depend on the electrode–tissue interaction, the lack of structural anatomical information on innervation and vascularization of the auricle restrain the current optimization of stimulation paradigms. For the first time, we employed high-resolution episcopic imaging (HREM) to generate histologic volume data from donated human cadaver ears. Optimal parameters for specimen preparation were evaluated. Anatomical 3D vascular and nerve structures were reconstructed in one sample of an auricular cymba conchae (CC). The feasibility of HREM to visualize anatomical structures was assessed in that diameters, occupied areas, volumes, and mutual distances between auricular arteries, nerves, and veins were registered. The selected region of CC (3 × 5.5 mm) showed in its cross-sections 21.7 ± 2.7 (mean ± standard deviation) arteries and 14.66 ± 2.74 nerve fibers. Identified nerve diameters were 33.66 ± 21.71 μm, and arteries had diameters in the range of 71.58 ± 80.70 μm. The respective occupied area showed a share of, on average, 2.71% and 0.3% for arteries and nerves, respectively, and similar volume occupancy for arteries and nerves. Inter-centroid minimum distance between arteries and nerves was 274 ± 222 μm. The density of vessels and nerves around a point within CC on a given grid was assessed, showing that 50% of all vessels and nerves were found in a radial distance of 1.6–1.8 mm from any of these points, which is strategically relevant when using stimulation needles in the auricle for excitation of nerves. HREM seems suitable for anatomical studies of the human ear. A 3D model of CC was established in the micrometer scale, which forms the basis for future optimization of the auricular VNS. Obviously, the presented single cadaver study needs to be validated by additional anatomical data on the innervation and vascularization of the auricle.

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects – a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Therapeutic applications of auricular vagus nerve stimulation (VNS) have drawn recent attention. Since the targeted stimulation process and parameters depend on the electrode–tissue interaction, the lack of structural anatomical information on innervation and vascularization of the auricle restrain the current optimization of stimulation paradigms. For the first time, we employed high-resolution episcopic imaging (HREM) to generate histologic volume data from donated human cadaver ears. Optimal parameters for specimen preparation were evaluated. Anatomical 3D vascular and nerve structures were reconstructed in one sample of an auricular cymba conchae (CC). The feasibility of HREM to visualize anatomical structures was assessed in that diameters, occupied areas, volumes, and mutual distances between auricular arteries, nerves, and veins were registered. The selected region of CC (3 × 5.5 mm) showed in its cross-sections 21.7 ± 2.7 (mean ± standard deviation) arteries and 14.66 ± 2.74 nerve fibers. Identified nerve diameters were 33.66 ± 21.71 μm, and arteries had diameters in the range of 71.58 ± 80.70 μm. The respective occupied area showed a share of, on average, 2.71% and 0.3% for arteries and nerves, respectively, and similar volume occupancy for arteries and nerves. Inter-centroid minimum distance between arteries and nerves was 274 ± 222 μm. The density of vessels and nerves around a point within CC on a given grid was assessed, showing that 50% of all vessels and nerves were found in a radial distance of 1.6–1.8 mm from any of these points, which is strategically relevant when using stimulation needles in the auricle for excitation of nerves. HREM seems suitable for anatomical studies of the human ear. A 3D model of CC was established in the micrometer scale, which forms the basis for future optimization of the auricular VNS. Obviously, the presented single cadaver study needs to be validated by additional anatomical data on the innervation and vascularization of the auricle. [ABSTRACT FROM AUTHOR]

Objective: To explore the effects of tactile stimulation using air pressure at the auricular branch of the vagus nerve on autonomic activity in healthy individuals., Methods: Three types of tactile stimulation were used in this study: continuous low-amplitude, continuous high-amplitude, and pulsed airflow. The tactile stimulations were provided to the cymba concha to investigate autonomic activity in 22 healthy participants. The mean heart rate (HR) and parameters of HR variability, including the standard deviation of R-R intervals (SDNN) and root mean square of successive R-R interval differences (RMSSD) were compared at baseline, stimulation, and recovery periods., Results: Two-way repeated measures ANOVA indicated a significant main effect of time on HR (p=0.001), SDNN (p=0.003), and RMSSD (p<0.001). These parameters showed significant differences between baseline and stimulation periods and baseline and recovery periods in the post-hoc analyses. There were no significant differences in the changes induced by stimulation type and the interaction between time and stimulation type for all parameters. One-way repeated measures ANOVA showed that HR, SDNN, and RMSSD did not differ significantly among the three time periods during sham stimulation., Conclusion: Parasympathetic activity can be enhanced by auricular tactile stimulation using air pressure, targeting the cymba concha. Further studies are warranted to investigate the optimal stimulation parameters for potential clinical significance.

Primary cervical dystonia is characterized by abnormal, involuntary, and sustained contractions of cervical muscles. Current ways of treatment focus on alleviating symptomatic muscle activity. Besides pharmacological treatment, in severe cases patients may receive neuromodulative intervention such as deep brain stimulation. However, these (highly invasive) methods have some major drawbacks. For the first time, percutaneous auricular vagus nerve stimulation (p VNS) was applied in a single case of primary cervical dystonia. Auricular vagus nerve stimulation was already shown to modulate the (autonomous) sympathovagal balance of the body and proved to be an effective treatment in acute and chronic pain, epilepsy, as well as major depression. p VNS effects on cervical dystonia may be hypothesized to rely upon: (i) the alteration of sensory input to the brain, which affects structures involved in the genesis of motoric and nonmotoric dystonic symptoms; and (ii) the alteration of the sympathovagal balance with a sustained impact on involuntary movement control, pain, quality of sleep, and general well-being. The presented data provide experimental evidence that p VNS may be a new alternative and minimally invasive treatment in primary cervical dystonia. One female patient (age 50 years) suffering from therapy refractory cervical dystonia was treated with p VNS over 20 months. Significant improvement in muscle pain, dystonic symptoms, and autonomic regulation as well as a subjective improvement in motility, sleep, and mood were achieved. A subjective improvement in pain recorded by visual analog scale ratings (0-10) was observed from 5.42 to 3.92 (medians). Muscle tone of the mainly affected left and right trapezius muscle in supine position was favorably reduced by about 96%. Significant reduction of muscle tone was also achieved in sitting and standing positions of the patient. Habituation to stimulation leading to reduced stimulation efficiency was observed and counteracted by varying stimulation patterns. Experimental evidence is provided for significantly varied sympathovagal modulation in response to p VNS during sleep, assessed via heart rate variability ( HRV). Time domain measures like the root mean square of successive normal to normal heart beat intervals, representing parasympathetic (vagal) activity, increased from 37.8 to 67.6 ms (medians). Spectral domain measures of HRV also show a shift to a more pronounced parasympathetic activity. [ABSTRACT FROM AUTHOR]

The viability of a new biophotonic alternative to conventional prescription‐drug‐based treatments is explored for inflammatory disease and mental health disorders using a non‐invasive drug‐free optogenetics‐based therapy to treat patients by optically stimulating selected afferent branches of the auricular vagus nerve transcutaneously via the outer ear using a high‐resolution, addressable array of organic light emitting diodes (OLED) manufactured on a flexible plastic substrate. Preliminary analysis and optical measurements indicate that our 620 nm flexible red OLED display technology is bright enough to induce therapeutic optical stimulation in optogenetically modified neural tissue. [ABSTRACT FROM AUTHOR]

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects - a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Objective: To observe and evaluate the clinical efficacy of transcutaneous vagus nerve stimulation (taVNS) at auricular concha for primary insomnia (PI) and affective disorder., Methods: A total of 35 patients who met the diagnosis standard of PI in Diagnostic and statistical manual of mental disorders (5th edition) were included. The self-developed auricular vagus nerve stimulator (TENS-200A) was applied at auricular concha, 30 min per treatment, twice a day, 5 days a week for consecutive 4 weeks. The follow-up visit was conducted at the end of 6th week. The Pittsburg sleep quality index scale (PSQI), 17-items Hamilton depression scale (17HAMD) and Hamilton anxiety scale (HAMA) were applied for evaluation. The PSQI, HAMA and 17HAMD were observed before and after treatment; the safety was also observed., Results: Compared before treatment, the PSQI was significantly decreased to (13.20±3.61) at the end of 2nd week ( P <0.05); compared before treatment, the 17HAMD and HAMA were significantly decreased at the end of 4th week and 6th week (all P <0.05). No adverse reaction was observed., Conclusions: The taVNS could not only relieve PI symptoms, but also improve the depressive and anxiety symptoms, in addition, it may have positive long-term efficacy and safety.