Investigating Hemodynamic Responses to Electrical Neurostimulation

Since the 1900s, the number of deaths attributable to cardiovascular disease has steadily risen. With the advent of antihypertensive drugs and non-invasive surgical procedures, such as intravascular stenting, these numbers have begun to level off. Despite this trend, the number of patients diagnosed with some form of cardiovascular disease has only increased. By 2030, prevalence of coronary heart disease is expected to increase approximately by 18% in the United States. By 2050, prevalence of peripheral arterial occlusive disease is expected to increase approximately by 98% in the U.S. No single drug or surgical intervention offers a complete solution to these problems. Thus, a multi-faceted regimen of lifestyle changes, medication, and device or surgical interventions is usually necessary. A potential adjunct therapy and cost-effective solution for treating cardiovascular disease that has been overlooked is neurostimulation. Recent studies show that using neurostimulation techniques, such as transcutaneous electrical nerve stimulation (TENS), can help to reduce ischemic pain, lower blood pressure, increase blood flow to the periphery, and decrease systemic vascular resistance. The mechanisms by which these hemodynamic changes occur is still under investigation. The primary aim of this thesis is to elucidate these mechanisms through a thorough synthesis of the existing literature on this subject. Neurostimulation, specifically TENS, is thought to modulate both the metaboreflex and norepinephrine release from sympathetic nerve terminals. To test the hypothesis that TENS increases local blood flow, decreases mean arterial pressure, and decreases cutaneous vascular resistance compared to placebo, in which the electrodes are attached but no electrical stimulation is applied, a protocol was developed to test the effect of neurostimulation on healthy subjects. Implementation of this protocol in a pilot study will determine if neurostimulation causes significant changes in blood flow using the most relevant perfusion measurement instrumentation. Before conducting this study, pre-pilot comparison studies of interferential current therapy (IFC) versus TENS, low frequency (4 Hz) TENS versus high frequency (100 Hz) TENS, and electrode placement on the back versus the forearm were conducted. The only statistically significant difference found was that the application of IFC on the back decreased the reperfusion time, meaning that the time required to reach the average baseline perfusion unit value after occlusion decreased. Further pre-pilot work investigating these different modalities and parameters is necessary to ensure that favorable hemodynamic changes can be detected in the pilot study

Noninvasive vagus nerve stimulation alters neural response and physiological autonomic tone to noxious thermal challenge.

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output

Interferential electrical stimulation improves peripheral vasodilatation in healthy individuals

BACKGROUND:Interferential electrical stimulation (IES), which may be linked to greater penetration of deep tissue, may restore blood flow by sympathetic nervous modulation; however, studies have found no association between the frequency and duration of the application and blood flow. We hypothesized that 30 min of IES applied to the ganglion stellate region might improve blood flow redistribution.OBJECTIVES:The purpose of this study was to determine the effect of IES on metaboreflex activation in healthy individuals.METHOD:Interferential electrical stimulation or a placebo stimulus (same protocol without electrical output) was applied to the stellate ganglion region in eleven healthy subjects (age 25±1.3 years) prior to exercise. Mean blood pressure (MBP), heart rate (HR), calf blood flow (CBF) and calf vascular resistance (CVR) were measured throughout exercise protocols (submaximal static handgrip exercise) and with recovery periods with or without postexercise circulatory occlusion (PECO+ and PECO -, respectively). Muscle metaboreflex control of calf vascular resistance was estimated by subtracting the area under the curve when circulation was occluded from the area under the curve from the AUC without circulatory occlusion.RESULTS:At peak exercise, increases in mean blood pressure were attenuated by IES (p<0.05), and the effect persisted under both the PECO+ and PECO- treatments. IES promoted higher CBF and lower CVR during exercise and recovery. Likewise, IES induced a reduction in the estimated muscle metaboreflex control (placebo, 21±5 units vs. IES, 6±3, p<0.01).CONCLUSION:Acute application of IES prior to exercise attenuates the increase in blood pressure and vasoconstriction during exercise and metaboreflex activation in healthy subjects.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FIPE-HCPA, Porto Alegre, BrazilUniversidade Federal de São Paulo (UNIFESP) Cardiovascular Surgery DepartmentHospital de Clinicas de Porto AlegreUniversidade de Brasilia Physical Therapy DepartmentUNIFESP, Cardiovascular Surgery DepartmentSciEL

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Development, Safety, Parametric Optimization, and Neurophysiological Effects

Cervically implanted vagus nerve stimulation (VNS) is a FDA-approved treatment for epilepsy and major depressive disorder (MDD). Additionally, VNS is a reemerging area of interest, showing promise in numerous animal studies with significant translatable applications. The cost, surgical risk, and human translation difficulty makes noninvasive VNS a highly-desired alternative. We have developed a transcutaneous auricular vagus nerve stimulation (taVNS) system that electrically stimulates the auricular branch of the vagus nerve (ABVN). We aimed to answer the following questions in this body of work: 1) whether taVNS is safe and feasible 2) if taVNS stimulates the vagus system similarly to implanted VNS 3) if the neurobiological effect of taVNS is similar to implanted VNS. We measured physiological recordings in healthy adults during taVNS to determine whether taVNS has vagus-mediated effects. In our first trial (n=15), we explored the physiological effects of 9 various stimulation parameter combinations (various pulse widths and frequencies) as a broad search of the physiological effect. A second, follow up trial was conducted (n=20) to determine the best candidate parameter that optimally activates the parasympathetic nervous system. Lastly, we developed and conducted a novel concurrent taVNS/fMRI trial (n=17) to determine the neurobiological effect of taVNS and its afferent targets. All three trials consisted of 2 visits each, in a randomized, controlled, crossover design in which taVNS was delivered to either the left tragus (active) or earlobe (control). The first physiological trial revealed relevant, immediate heart rate decreases during taVNS followed by a sympathetic rebound upon termination of stimulation. Of the nine parameters tested, two had the largest effect on heart rate (500µs, 10Hz; 500µs, 25Hz). These two parameters were tested in the follow-up trial, which demonstrated that both parameters decrease heart rate, with 500µs 10Hz having the largest physiologic effect. Lastly, findings from the taVNS/fMRI trial demonstrate the neurobiological effect of taVNS mimics that of cervically implanted VNS and targets several cortical and subcortical vagus afferent pathway targets. taVNS in our paradigms was feasible, safe, and demonstrated neurobiological effects that are similar to implantable VNS. Future trials should conduct parametric optimization using the taVNS/fMRI protocol as it reliably targets vagus nerve afferents as well as further explore optimizing taVNS as a possible therapeutic and research tool

The feasibility of implementing a novel electrical stimulation device in the self-management of hand burn pain

Burns are widely acknowledged as one of the most painful injuries experienced, and poorly controlled pain following burn injury has been linked to reduced psychological adjustment, lower quality of life, and increased risk of developing a chronic pain state. Transcutaneous electrical nerve stimulation has been used for pain relief in a range of medical conditions, and may have the potential to reduce pain and analgesic consumption for burns patients. The burn care environment presents unique challenges to the introduction of new interventions, and the feasibility of introducing a novel form of electrical stimulation into this environment has not been tested. This single case experimental design study explores the feasibility of engaging burns patients and staff in the use of a novel electrical stimulation device, which may offer solutions for some of the limitations previously identified with traditional electrical stimulation. Four outpatients, with minor hand burns, self-applied the device over a period of up to 13 days. Multiple sources of data were gathered, both at home, and in the clinic during wound care procedures; from participants, nursing staff and the researcher, to obtain different perspectives. Each case was analysed separately regarding changes at the time the device was introduced. Data collected included ratings of pain, anxiety and confidence in the ability to manage their own pain. Participant and staff ratings on ease of use and interference of the device with regular activities were also explored, along with the level of motivation to use the device. Analysis of trends and relationships between multiple data sources demonstrated that, for these participants with hand burns, the self-application of a novel electrical stimulation device was feasible. Recommendations for further research and clinical practice are outlined

Complimentary Care: Opportunity to Explore Non-Drug Pain Management

Aristotle (4th century B.C.), he said pain as emotion, being the opposite of pleasure. But Buddha says “Pain is the outcome of sin”, as proof that an independently was possessed by demons. In some religions it is the cost of attachment. Medical management thus may be less of a preference than Spiritual counseling. Many non-physiologic factors (psychological, familial and societal attitudes, life stressors, and cultural or spiritual) contributing to the experience of and response to pain. Emotional stress, like, anxiety and depression known a key play in understanding of pain. Endless hurt is related with expanded dimensions of burdensome side effects, anxiety, and insomnia paying little heed to disability status. It has both modifiable factors (mental health, co-morbidities, smoking, alcohol, obesity, physical activity/exercise, sleep, nutrition, economic status and occupational) and non-modifiable factors (age, sex, cultural and socioeconomic background, history of trauma/ injury/ interpersonal violence, heritage). Chronic pain affects 20% of the European population and is commoner in women, older people, and with relative deprivation

Use Of Different Electrical Stimulations For Treating Pain In Women With Temporomandibular Disorders [utilização De Diferentes Estimulações Elétricas Para O Tratamento Da Dor Em Mulheres Com Disfunção Temporomandibular]

Objective: To analyze pain intensity in individuals with temporomandibular disorder (TMD) who were treated with ten sessions of transcutaneous electrical nerve stimulation (TENS) or high voltage electrical stimulation (HVES). Methods: Twenty-four women (22.98±1.86 years old) with a diagnosis of TMD in accordance with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were selected. Sixty percent of the participants had a diagnosis of TMD classified as group Ia and 40% as Ia and IIa. They were divided into two groups named TENS group (TG) and high-voltage group (HVG). Each participant received ten applications of either TENS (10Hz, modulated at 50%, 200μs and motor threshold intensity) or HVES (10Hz, twin pulses of 20μs each at intervals of 100μs between the twin pulses, 100volts and positive pole) twice a week for 30 minutes. To measure the pain intensity, a visual analog scale (VAS) was used. Statistical analyses were performed using t test and simple linear regression. Results: Comparison of the pre- and post-TENS conditions showed diminished pain intensity (p<0.05) in most sessions except for sessions 6, 7 and 8. In contrast, HVES reduced the pain intensity in all sessions (p<0.05). Evaluation of the pre-application values showed that both treatments decreased the pain intensity uniformly over the ten sessions (p<0.05). Conclusions: TENS and HVES both promoted reductions in pain intensity in women with TMD. 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Porto Alegre: Artme

Role of the autonomic nervous system in the genesis of cardiac arrhythmias : pathophysiology and therapy implications

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2021O sistema nervoso autónomo é responsável pela manutenção do normal funcionamento cardíaco, através de vias dinâmicas de feedback aferente e eferente entre os seus diferentes níveis. A doença cardíaca pode levar a um “remodelling” neuronal e disfunção simpatovagal, o que tem sido implicado na iniciação e manutenção de arritmias cardíacas auriculares e ventriculares. Os mecanismos complexos através dos quais a desregulação autonómica predispõe à arritmogénese são diferentes entre arritmias. Na fibrilhação auricular, o aumento da atividade de ambos os sistemas simpático e parassimpático é proarrítmico. Em contraste, na fibrilhação ventricular no contexto de isquemia miocárdica, a ativação simpática é o desencadeante mais comum. Na maioria dos síndromes de arritmias hereditárias, a estimulação simpática induz taquiarritmias ventriculares e morte súbita cardíaca. A identificação de desencadeantes autonómicos específicos tem sugerido que várias terapêuticas de neuromodulação poderão contribuir para a prevenção e tratamento de diferentes arritmias. A neuromodulação é uma terapêutica bem estabelecida no síndrome do QT longo, mas continua ainda sob investigação quanto à sua utilização em outras arritmias. Nesta revisão, iremos apresentar um breve resumo da anatomia e fisiologia básicas do sistema nervoso autónomo cardíaco e explicar o seu papel na patogénese de arritmias cardíacas, incluindo fibrilhação auricular e arritmias ventricualres, particularmente no contexto de isquémia miocárdica e canalopatias hereditárias. Por fim, iremos apresentar os avanços recentes bem como as potenciais limitações da neuromodulação, uma estratégia emergente na gestão de doentes com arritmias refratárias, por permitir restaurar o equilíbrio entre as componentes simpática e parassimpática do sistema nervoso autónomo.The autonomic nervous system is responsible for the maintenance of normal cardiac function, through dynamic afferent and efferent feedback loops between its different levels. Cardiac disease can lead to neural remodelling and sympathovagal imbalances, inducing autonomic dysregulation, which is known to play an important role in the initiation and maintenance of atrial and ventricular cardiac arrhythmias. The complex mechanisms by which autonomic dysregulation predisposes to arrhythmogenesis are different between arrhythmias. In atrial fibrillation, increased activity of both sympathetic and parasympathetic systems is proarrhythmic. In contrast, in ventricular fibrillation in the setting of myocardial ischaemia, sympathetic activation is the most common trigger. In most inherited arrhythmia syndromes, sympathetic stimulation induces ventricular tachyarrhythmias and sudden cardiac death. The identification of specific autonomic triggers has suggested that several neuromodulatory therapies might contribute to the prevention and treatment of different arrhythmias. Neuromodulation is a well-established therapy in long QT syndrome, but it is still under investigation regarding its use in other arrhythmias. In this review, we will present a brief resume of the basic anatomy and physiology of cardiac autonomic nervous system and explain its role in the pathogenesis of cardiac arrhythmias, including atrial fibrillation and ventricular arrhythmias, particularly in the context of myocardial ischaemia and inherited channelopathies. Then, we will present the recent advances as well as the potential limitations of neuromodulation, which is emerging as an alternative in the management of patients with refractory arrhythmias, allowing to restore the balance between sympathetic and parasympathetic branches of the autonomic nervous system