Title: The Mystery of Medicine: The Autonomic Nervous System Dysfunction

Abstract: The autonomic nervous system in our body adapts to changes in the internal and external environment and controls vital structures such as the heart, vessels, intestines, and reproductive organs in our body. It mainly consists of two components: the sympathetic system, which causes the “fight or flight” response, especially in the presence of danger, a threat or in a state of panic, etc.; and the parasympathetic nervous system, whose intrinsic properties shortly referred to as “rest and digest” help to calm down the body, allow growth and development and lower the level of stress.

As the stress factors in our routine life rise, the autonomic nervous system dysfunction may cause numerous disorders and diseases including depression, headaches, gastrointestinal disorders, sleep problems, cardiac problems, and etc. Understanding the autonomic nervous system and its dysfunctions will actually increase your awareness with regard to these problems, and potential solutions.

Author: Ali Veysel Özden, M.D., Ph.D.

Articles and Clinical Researches

Title: Acute Effect of Auricular Vagus Nerve Stimulation on Cycle
Ergometer Test and Physiological Parameters in Healthy
Young Individuals: A Pilot Study

Background: This study is to investigate the effect of non-invasive auricular VNS on cycle ergometer test and physiological parameters in healthy individuals.

Methods: 46 people participated in the study. The participants were randomly divided into 3 groups as Above Threshold, Under Threshold and Control according to the sensation of electrical current on ears. The participants were evaluated 3 times; before the application, after the first and second bicycle exercises. Numerical pain scale, pulse rate, blood pressure, respiratory rate, and distance travelled during exercise for cycle ergometer test.

Results: There was no significant difference in 1st measurement, 2nd measurement, 3rd measurement of pulse rate, saturation value and performance in the control group, sub-threshold group and above threshold group (p ˃ 0.05). The 2nd measurement of NPS value was significantly lower in the above threshold group than in the control group and the below threshold group (p ˂ 0.05). The 1st measurement, 2nd measurement, 3rd measurement respiratory rate and 3rd measurement diastolic pressure values were significantly higher in the sub-threshold group (p ˂ 0.05).

Conclusion: In healthy individuals, short-term non-invasive auricular VNS does not affect cycle ergometer test during exercise. This may be due to the fact that the application time is kept short and the application is a single time. In VNS application, feeling the current and/or current intensity may affect parameters such as respiratory rate and blood pressure.

Authors: Sefa Haktan HATIK, PT, Berkay Eren Pehlivanoğlu, Mesut ARSLAN, Çilem TAŞKIN, and Ali Veysel ÖZDEN

Title: Short-term effectiveness of auricular vagus nerve stimulation in patients with myofascial pain syndrome

Objectives: To evaluate the effect of auricular vagus nerve stimulation (VNS) applied in addition to ischemic compression and stretching exercises on pain, trigger point (TP) sensitivity, grip strength, quality of life and autonomic functions in patients with myofascial pain syndrome (MPS).

Methods: Sixty patients, who had neck pain, met the diagnostic MPS criteria of Travell and Simons were included in the study. The subjects were randomly divided into VNS group (n = 30) or control group (n = 30). Each group performed 10 sessions of TP ischemic compression and stretching exercises (5 days/week). Ten sessions of 30-minute long auricular VNS were added to the treatment in VNS group. Pain severity [Visual Analogue Scale (VAS)], TP sensitivity (algometer), grip strength (Jamar dynamometer), quality of life [Short Form-36 (SF-36)] and autonomic function [Composite Autonomic Symptom Scale-31 (Compass-31)] were evaluated before and after 10 sessions of treatment.

Results: The VAS, algometer and Jamar measurements showed significant improvement in both groups. A statistically significant improvement was found in orthostatic intolerance, secretomotor and pupillomotor subscales of Compass-31 scale in the VNS group following the treatment (p < 0.05) while no significant difference was observed in the control group (p > 0.05). The control group showed significant improvement in all parameters of SF-36 scale, while the VNS group showed significant improvement in physical function, social functionality and pain parameters (p < 0.05). The changes in the VAS, algometer, Jamar scores and secretomotor subscale of the Compass-31 scale were statistically higher in the VNS group than in the control group (p < 0.001, p < 0.001, p = 0.001 and p = 0.011, respectively).

Conclusions: It can be argued that auricular VNS increases the effectiveness of ischemic compression and stretching exercises in patients with MPS. Further and detailed studies are needed in which the effect of VNS alone or in combination with other treatments in patients with MPS is examined and the physiological mechanisms are investigated.

Keywords: Myofascial pain syndrome, auricular vagus nerve stimulation, ischemic compression, autonomic nervous system, quality of life

Authors: Simay Ünal, Dilber Karagözoğlu Çoşkunsu, Sefa Haktan Hatık, Ali Veysel Özden

Title: The Effect of Vagus Nerve Stimulation Applications on Taste and Smell Loss in COVID-19 Syndrome: Case Report

Abstract: Loss of the sense of taste and smell is a common side effect of Covid 19. It is thought that transcutaneous ear vagus nerve stimulation may affect taste and smell as a result of neural connections. We present a 27-year-old female participant diagnosed with loss of taste and smell for more than 1 year. The Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test was used to test the sense of smell. To test the sense of taste, 3 drops of taste test were applied. It was found that during the application period of 1 session per day for 15 days, there was a progressive improvement in the sense of taste and smell.

Authors: Berkay Eren Pehlivanoglu , Sanem Guven , Sefa Haktan Hatik , Ali Veysel Ozden

Title: The effect of auricular vagus nerve stimulation on electroencephalography and electromyography measurements in healthy persons.

Objectives: Auricular vagus nerve stimulation (VNS) is a non-invasive treatment
modality. Opinions that it can be used in the treatment of various clinical problems
have gained importance in recent years. In this study, it was aimed to lay the
groundwork for the use of the auricular VNS in different ears.
Methods: Healthy individuals (n = 90) were divided into three groups: unilateral
left (n = 30), unilateral right (n = 30), and bilateral (n = 30) auricular VNS.
Electroencephalography (EEG) and electromyography (EMG) measurements
were performed before and after auricular VNS (10 Hz, 300 μs, 20 min) for a
single session.
Results: An increase in wrist extensor muscles activation was detected on the
contralateral side of the auricular VNS application side. It has been observed that
there is a general decrease in the power of high-frequency waves and an increase
in the power of lower-medium frequency waves in various parts of the brain.
Conclusion: Our findings suggest that the projection of the auricular VNS in the
central nervous system may also affect the corticospinal tracts.

Authors: Gülşah Konakoğlu, Ali Veysel Özden, Hakan Solmaz, Celaleddin Bildik4

Title: Non-invasive vagus nerve stimulation in a hungry state decreases heart rate variability and wanting of a palatable drink

Abstract: Vagus nerve signals from the gut to brain carry information about nutrients and drive food reward. Such signals are disrupted by consuming large amounts of high-calorie foods, necessitating greater food intake to elicit a similar neural response. Non‐invasive vagus nerve stimulation (nVNS) via a branch innervating the ear is a candidate treatment for obesity in humans. There is disagreement on the optimal location of nVNS in the ear for experimental and clinical studies. There are also no studies comparing nVNS in hungry and full states. We aimed to compare ear position(s) for nVNS and explore the effects of nVNS during hungry and full states on proxies for autonomic outflow (heart-rate variability) and efferent metabolism (gastric frequency and resting energy expenditure).

In a within-subject design, 14 participants (10 women, on average 29.4 +/- 6.7 years old) received nVNS in four different locations (cymba conchae, tragus, earlobe, or tragus AND cymba conchae) on separate days. In each session, participants were asked to consume a palatable chocolate flavored milk. With electrography on the abdomen and indirect calorimetry in a canopy, we measured electro-cardiogram, electro-gastrogram and resting energy expenditure for 15 minutes before and at least 35 minutes after consumption of the palatable drink. We also collected ratings of the palatable drink and internal and other states.

Pre-drink consumption (in a hungry state) we observed no differences in the effect of location of acute nVNS on resting energy expenditure and gastric frequency. However, nVNS in cymba conchae decreases heart-rate variability and ratings of how much participants want to consume the drink. After drink consumption and with continued nVNS, gastric frequency is unchanged, and resting energy expenditure increases regardless of stimulation location. Heart-rate variability decreases in all locations, except cymba conchae. We also observe a trend for an increase in gastric frequency in late post-drink consumption time-points in cymba conchae. These results suggest that nVNS in the cymba conchae in a hungry state has a similar acute effect on vagal tone as food consumption: to decrease heart rate variability. This effect then negates the usual postprandial effects of a decrease in heart rate variability as seen in the other nVNS locations. This suggests that nVNS in cymba conchae may act primarily on vagal afferent autonomic (and only modestly on metabolic output) in a similar way as food consumption does.

Authors: Zeynep Altınkaya, Lina Öztürk, İlkim Büyükgüdük, Hüseyin Yanık, Dilan Deniz Yılmaz, Berçem Yar, Evren Değirmenci, Uğur Dal, Maria Geraldine Veldhuizen

Title: The use of positive airway pressure and transauricular vagus nerve stimulation in a paroxysmal hemicranias and assessment of sympathetic skin response

Abstract: Paroxysmal hemicrania is characterised by severe short-term unilateral headaches that are associated with ipsilateral cranial autonomic symptoms. A rare headache type, paroxysmal hemicrania is included in the trigeminal autonomic cephalgia group of primary headache. The relationship between paroxysmal hemicrania and sleep apnoea has not been previously reported in the literature. Noninvasive vagus nerve stimulation offers an alternative treatment option for patients who cannot tolerate indomethacin or other traditional treatments. We report the case of a female patient with sleep apnoea and paroxysmal hemicrania who could not use indomethacin and other therapies. Her headaches temporarily regressed with positive airway pressure treatments and positively responded to transauricular vagus nerve stimulation. We evaluated the stimulatory effect of this treatment by examining the patient’s sympathetic skin responses.

Authors: Metin, Kübra Mehel; Meriç, Olcay Tosun; İnan, Levent Ertuğrul; Yoldaş, Tahir Kurtuluş

Objective: The aim of this study is to investigate the effect of non-invasive auricular VNS (Vagus Nerve Stimulation) on sportive performance and physiological parameters in healthy individuals.

Material and Method: 46 healthy young individuals aged 19.2(±1.5) years participated in the study. The participants were randomly divided into 3 groups as Above Threshold Group (n:15; 10 females, 5 males), Under Threshold Group (n:15; 10 females, 5 males), and Control Group (no stimulation) (n:16; 11 females, 5 males) according to the sensation of electrical current on ears. The participants were evaluated 3 times; before the application, after the first and second bicycle exercises. Numerical pain scale (NPS), pulse rate, blood pressure, respiratory rate, and distance traveled during exercise for sportive performance were recorded in kilometers as the evaluation method. The stimulation was done during the first bicycle exercise with 5 minutes of duration. The Kruskal-wallis, mann-whitney u test were used for the quantitative independent data obtained. In the analysis of qualitative independent data, chi-squared test was used.

Author: Sefa Haktan Atık

Title: The Impact of Auricular Vagus Nerve Stimulation on Pain and Life Quality in Patients with Fibromyalgia Syndrome

Abstract: The purpose of this study is to evaluate the impact of auricular vagus nerve stimulation, applied in conjunction with an exercise treatment program, on pain and life quality in patients with fibromyalgia syndrome (FMS). To achieve the study objectives, 60 female patients between the ages 18 and 50, with diagnosed FMS according to the American College of Rheumatology (ACR) 2010 diagnostic criteria, were randomly divided into 2 groups of 30. The first group was assigned 20 sessions of a home-based exercise program, while the second group was assigned 20 sessions of auricular vagus nerve stimulation and 20 sessions of a home-based exercise program. Patients were assessed before and after the treatments using the Visual Analog Scale (VAS) for pain, Beck Depression Scale for depression, Beck Anxiety Scale for anxiety, Fibromyalgia Impact Questionnaire (FIQ) for functional evaluation, and Short Form-36 (SF-36) for life quality. In this randomized controlled trial, comparisons within the groups revealed that both groups had statistically significant improvements in pain, depression, anxiety, functionality, and life quality scores (p < 0.05), while comparisons across the groups revealed that the group experiencing the vagus nerve stimulation had no statistically significant differences between the baseline scores, except for those of SF-36’s subparameters of physical function, social functionality, and pain. In fact, comparisons across the groups after the interventions revealed that the group experiencing the vagus nerve stimulation had better scores but not statistically significant. From the analysis of this data, we observed that vagus nerve stimulation in FMS treatment did not give additional benefit together with exercise, except for three subparameters of SF-36. It was identified that further studies which separately investigate the effects of vagus nerve stimulation and exercise on FMS with longer follow-up periods and an increased number of patients are needed.

Authors: Nazlı Kutlu, Ali Veysel Özden, Hasan Kerem Alptekin, Jülide Öncü Alptekin

Title: Extracellular and Intracellular Fluid Shifts on the Onset of Transcutaneous Auricular Vagus Nerve Stimulation

Abstract: In this paper, we propose multifrequency body impedance measurement technique for monitoring the onset of vagus nerve stimulation. In response to transcutaneous electrical vagus stimulation, changes occur in body fluids i.e. fluid shifts in extracellular and intracellular media that can be assessed by Cole parameters Re and Ri before and after stimulus, by measuring single side impedance spectroscopy (from 3 kHz to 1MHz) between wrist and ankle. Following a resting period of 5 minutes in supine position, auricular vagus nerve was stimulated for 3 minutes and BIS performed every 10 seconds, on 23-27 years old, 5 healthy subjects. During the stimulation phase, either an increase or a decrease was observed in extracellular and intracellular fluids. In 3 of the subjects, an ECF decrease of 0.02% per kg was compensated by 0.02 to 0.06% per kg increase in ICF; with a correlation coefficient of -0,70 to -0,79; suggesting fluid shifts between ECF and ICF. With the other 2 subjects, both ECF and ICF decreased by about 0.02% per kg. The study was performed with a limited number of participants; to reach statistically meaningful results measurements will be performed over a larger sample size.

Authors: Y. Ülgen, B. Büyüksaraç, B. Tunç and H. Solmaz

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