Vagus Nerve Stimulation

1st Edition - November 16, 2024
Editors: Peter Staats, Cenk Ayata, Imanuel Lerman, Alaa Abd-Elsayed
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 1 6 9 9 6 - 4
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 6 9 9 7 - 1

In the complex realm of our physiology, the vagus nerve stands as a silent orchestrator, influencing health and disease in ways that have long been underestimated. Vagus Nerve… Read more

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In the complex realm of our physiology, the vagus nerve stands as a silent orchestrator, influencing health and disease in ways that have long been underestimated. Vagus Nerve Stimulation delves into the profound significance of this 10th cranial nerve, tracing its course through the body and illuminating its role as a vital component of the parasympathetic nervous system.

This comprehensive reference, contributed by leading experts at the forefront of medical science, unveils the groundbreaking field of vagus nerve stimulation—a non-invasive approach to harness the body's innate potential for health optimization, inflammation control, and disease modification. Contributed by leading experts in the field, this comprehensive volume serves as a compendium of current knowledge about stimulating the vagus nerve in many different disease states. This book starts with the foundational insights in Basic Science and Technical Considerations. From there, it continues to Neurologic Conditions, where chapters explore applications for epilepsy, cluster headaches, and concussions. Evolving Therapy for Neurologic Conditions introduces cutting-edge treatments for acute ischemic stroke, synaptic plasticity, and neurodegenerative disorders. The book extends into Psychiatric and Somatic Conditions, providing insights into anxiety, depression, addiction disorders, and more. Conventional Inflammatory Conditions shed light on vagus nerve stimulation's role in combatting sepsis, immune-mediated inflammatory diseases, and metabolic syndrome, among others. Concluding with a foray into Oncology, the book highlights the potential of vagus nerve stimulation in addressing the lingering effects of long covid and migraine. With an authoritative blend of scientific rigor and practical application, this reference serves as an indispensable guide to the vast landscape of vagus nerve stimulation, transforming our understanding of health and wellness.

Vagus Nerve Stimulation
Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Preface
Introduction
Section I: Why is the vagus getting so much attention
Chapter 1 Vagus insufficiency syndrome
Abstract
Keywords
Introduction
Anatomy of the vagus nerve
Explaining medically unexplained symptoms
Traditional treatment of MUSs
Vagus insufficiency syndrome
History of vagus nerve stimulation
Noninvasive VNS
Cervical nVNS
Headache disorders
Episodic cluster headache
Chronic cluster
Acute treatment of migraine
Prevention of migraine
Novel diseases being studied for treatment with VNS
Fibromyalgia
Rheumatoid arthritis
Sjögren’s Syndrome
Asthma
Posttraumatic stress disorder
Gastrointestinal dysfunction
Anxiety and depression
Building the rationale for vagal control of MUS
Exploring the economic impact of MUS
Vagus nerve stimulation in vagus insufficiency
Conclusion
References
Chapter 2 Randomized controlled studies do not reflect the complexity of chronic disease, including the vagal response
Abstract
Keywords
Conflict of interest statements
Acknowledgments
Common links to chronic illnesses
Threat physiology
Allostatic load
Overall resilience of the nervous system
Root causes
Obstacles to treatment
Prospective randomized studies are insufficient in defining “standard of care”
An example treatment paradigm
Overview of solutions
Conclusion
References
Chapter 3 Vagus nerve stimulator (VNS)—What the surgeon needs to know
Abstract
Keywords
Introduction
Indications
Contraindications
VNS hardware
Leads
Implantable pulse generators
Surgical noninplantable accessories
Nonsurgical accessories
De novo VNS system implantation
Preoperative work-up
Surgical technique
Programming
Postoperative regimen
Complications
Side effects of VNS
MRI compatibility
Electrosurgery
IPG replacement
Lead revision
Explantation of entire VNS system
References
Chapter 4 Noninvasive vagus nerve stimulation: History, mechanisms, indications, and obstacles
Abstract
Keywords
Introduction
History of vagus nerve stimulation
Relevant anatomy of the vagus nerve
Mechanism
Indications
Measurement of vagus nerve function
Part one: Cognitive approaches
Mindfulness and biofeedback
Deep breathing and muscle relaxation techniques
External approaches to vagus nerve stimulation
Cold water immersion
Safe and sound protocol
Vagal maneuvers
Noninvasive vagus nerve stimulation
Electromagnetic field therapy
Obstacles to the use of noninvasive vagus nerve stimulation
Technical challenges
Variable response rates
Device limitations
Patient education and acceptance
Regulatory and reimbursement issues
Lack of long-term data
Future directions
Conclusions
References
Chapter 5 Exploring vagus nerve stimulation through the lens of the polyvagal theory☆
Abstract
Keywords
Evolution and the emergence of a ventral vagal circuit
A functional social engagement system
Sensory pathways of the social engagement system: Potential portals to stimulate vagal function
Vagal pathways
Vagus nerve stimulation: Assumed mode of action
Ventral vagal complex: A portal for vagus nerve stimulation
Role of afferents in vagus nerve stimulation
Recruiting the acoustic efferent limb of the social engagement system: A portal to stimulate vagal efferent activity
Vagal brake
Summary
References
Section II: Neurologic conditions
Chapter 6 Vagus nerve stimulation for the management of epilepsy
Abstract
Keywords
Introduction
Mechanism of action
Local effects
Central effects
Effects over neurochemistry, neurotransmitters, and neuroinflammatory pathways
Clinical use and efficacy
Closed-loop stimulation
Quality-of-life improvement
SUDEP and VNS
Side effects of VNS
Practical aspects of programming and maintenance of the VNS device
Predicting treatment outcomes
Patient selection
Conclusions and future directions
References
Chapter 7 Noninvasive vagus nerve stimulation in migraine treatment
Abstract
Keywords
Introduction
Migraine clinical presentation
Migraine pathophysiology
Migraine pharmacotherapy and limitations
Mechanism of action of noninvasive vagus nerve stimulation
Noninvasive vagus nerve stimulation efficacy in migraine treatment
Noninvasive vagus nerve stimulation safety
Migraine treatment with noninvasive vagus nerve stimulation
References
Chapter 8 Vagal nerve stimulation in rare headache disorders
Abstract
Keywords
Introduction
History of VNS
Epilepsy studies
Depression studies
Physiology of VNS in headache disorders
Modalities of VNS
VNS in cluster headache
VNS in indomethacin-sensitive headaches
VNS in SUNA/SUNCT
References
Chapter 9 Vagus nerve stimulation for the management of traumatic brain injury
Abstract
Keywords
Introduction
The history of electrical neuromodulation
Electroconvulsive therapy
Deep brain stimulation
Vagus nerve stimulation
Cranial nerve X: Vagus nerve
Anatomy
Mechanisms of action
Vagus nerve stimulation approaches
Implanted devices
Transcutaneous
Off-label uses and future applications
tVNS for TBI: A pilot study
Rationale for the study
Study design
Preliminary results
Limitations
Conclusion
References
Section III: Evolving therapy for neurologic conditions
Chapter 10 Vagus nerve stimulation in acute stroke: Review based on current modalities and emerging trends
Abstract
Keywords
Introduction
Overview of acute strokes
Pathophysiology of acute strokes
Clinical manifestations and consequences
Introduction to vagus nerve stimulation
Historical background of VNS
Application of VNS in neurological disorders
VNS in acute stroke: Mechanisms and rationale
Mechanisms underlying VNS in stroke recovery
Rationale for using VNS in acute stroke management
Preclinical studies supporting the use of VNS in stroke
Overview of clinical trials investigating VNS in acute stroke patients
Ongoing trials
Current modalities of VNS in acute stroke
Noninvasive vagus nerve stimulation
Electrical parameters of VNS
Clinical efficacy of VNS in acute stroke
Summary of clinical studies evaluating the efficacy of VNS in acute stroke patients
Analysis of outcomes such as functional recovery, neurological deficits, and quality of life
Emerging modalities and future directions
Noninvasive VNS techniques
Potential advantages and limitations compared to invasive VNS
Investigation of VNS combined with other therapeutic modalities
Synergistic effects and rationale for combination therapies
Novel targets and mechanisms
Advances in understanding the neurobiological mechanisms underlying VNS efficacy
Predictive biomarkers
Personalized medicine approaches for optimizing VNS treatment in acute stroke patients
Conclusion
References
Chapter 11 Using vagus nerve stimulation to direct synaptic plasticity and treat neurological disease
Abstract
Keywords
Introduction
Summary of findings from nonclinical studies
Rationale for the use of VNS paired with rehabilitation
VNS paired with rehabilitative training improves recovery of motor function in multiple rat models of brain injury
VNS paired with rehabilitative training improves recovery in rat models of SCI
Summary of findings from clinical research
VNS is widely used and safe
VNS paired with rehabilitation improves recovery after neurological injury
Conclusions
References
Chapter 12 Vagus nerve stimulation for the management of tinnitus
Abstract
Keywords
Introduction
Pathophysiology
Treatments for tinnitus
Sound paired vagus nerve stimulation for tinnitus
How does sound paired VNS exert its clinical benefit?
Vagus nerve stimulation and tinnitus
Conclusion
References
Chapter 13 Vagus nerve stimulation for the management of neurodegenerative disorders
Abstract
Keywords
Introduction
Mechanism of action
Contraindications
Indications
Parkinson’s disease
Alzheimer’s disease
Traumatic brain injury
Stroke
Mild cognitive impairment
Complications
References
Chapter 14 Vagal nerve stimulation for cognitive and performance enhancement
Abstract
Keywords
Introduction
The historical context of VNS in medical applications
The concept of enhancing cognition through VNS
Anatomy and function of the vagus nerve
Role of the vagus nerve in the autonomic nervous system
The connection between the vagus nerve and cognitive processes
Types of devices
Mechanisms of VNS in performance enhancement
Norepinephrine pathways
Acetylcholine pathway
GABA
Dopamine
Cognitive functions and VNS
Human conditions
Anxiety
Posttraumatic stress disorder
Sleep disorder
VNS and Alzheimer’s
Challenges and considerations
Future directions and research opportunities
Conclusion
References
Chapter 15 Vagus nerve stimulation for the management of chronic pain
Abstract
Keywords
Introduction
Anatomy and physiology of the vagus nerve with regards to nociceptive pathways
Influence of vagal activity on pain levels
Rationale for treatment
Animal studies
Human studies
Areas for future research
Conclusion
References
Section IV: Psychiatric and somatic conditions
Chapter 16 Vagus nerve stimulation for the management of depression and anxiety
Abstract
Keywords
Major depressive disorder
Anxiety disorders
Pathophysiology of depression and anxiety
Vagus nerve anatomy and VNS
Mechanism of action of vagus nerve stimulation in depression and anxiety
The history of VNS
The beginning of VNS for depression
VNS randomized control studies for depression
Further VNS studies for depression
Meta-analysis of VNS for depression
VNS for anxiety-related disorders
Noninvasive VNS
Clinical indications
Adverse effects
Conclusions
References
Chapter 17 Application of vagal nerve stimulation to post-traumatic stress disorder
Abstract
Keywords
Introduction
Neurobiology of PTSD and stress-related psychiatric disorders
Neural changes
Hypothalamic–pituitary–adrenal Axis and PTSD
Inflammatory responses in PTSD and related disorders
Cognitive decline in PTSD
Neuromodulation in stress-related psychiatric disorders
Vagus as a treatment target for PTSD
Vagal nerve stimulation as a PTSD treatment modality
Acute effects of tVNS in trauma-exposed individuals without PTSD
Acute physiological effects of tVNS in individuals with PTSD
Future directions and conclusions for PTSD and vagal nerve stimulation
Avenues for future research
Conclusions
References
Chapter 18 Vagus nerve stimulation for the management of fibromyalgia
Abstract
Keywords
Part 1: Introduction to and pathophysiology of fibromyalgia
Part 2: Mechanisms of vagus nerve stimulation
Autonomic modulation and neuroplasticity
Cholinergic antiinflammatory pathway
Clinical trials of VNS for fibromyalgia and chronic overlapping pain conditions
Part 5: Safety considerations
Conclusions/key points/recommendations
References
Chapter 19 Vagus nerve stimulation for the management of visceral pain
Abstract
Keywords
Vagus nerve stimulation in chronic visceral pain
Visceral pain
Anatomy of the vagus nerve
Mechanism of action of VNS in chronic visceral pain
Mechanism of vagus nerve stimulation in antinociception
Vagus nerve stimulation techniques and devices
Evidence for vagus nerve stimulation for chronic visceral pain
Conclusion
References
Chapter 20 Vagus nerve stimulation for the management of addiction disorders
Abstract
Keywords
Introduction and background
Vagus nerve and its multifaceted roles
The neurobiology of addiction: Reward pathway, vagus nerve, and potential therapies
The emergence of neuromodulation therapies for addiction treatment
Challenges and limitations of VNS for addiction treatment
Future directions for VNS and addiction
Summary and conclusion
References
Section V: Vagus nerve stimulation and inflammation
Chapter 21 Vagal nerve stimulation for the management of sepsis
Abstract
Keywords
Sepsis
Bidirectional communication between the immune and nervous systems
VNS in preclinical models of sepsis and systemic inflammation
Characterization of the CAP
Antiinflammatory mechanisms of vagus nerve stimulation
Vagus nerve stimulation inhibits inflammation in clinical studies
Implantable VNS systems
Transcutaneous VNS systems
Concluding remarks
References
Chapter 22 Vagus nerve stimulation for the management of immune-mediated inflammatory diseases
Abstract
Keywords
Introduction to vagus nerve and the immune reflex
The cholinergic antiinflammatory pathway
Hypothalamic–pituitary-adrenal axis
Brain-gut axis
Vagus nerve stimulation
VNS in immune-inflammatory diseases: from mouse models to humans
Rheumatoid arthritis
Inflammatory bowel disease
VNS studies in other immune-inflammatory diseases
Primary Sjögren’s syndrome
Scleroderma
Systemic lupus erythematosus
Knowledge gap/future research needs
References
Chapter 23 Vagus nerve stimulation for the management of inflammatory bowel disease and the cholinergic antiinflammatory pathway
Abstract
Keywords
Introduction
Ulcerative colitis
Crohn’s disease
Diagnosis
Treatment
Complications of IBD
Cholinergic antiinflammatory pathway and the effect of the vagus on intestinal barrier function
Where might vagus nerve stimulation fit into the IBD treatment paradigm in the future?
References
Chapter 24 Clinical applications of vagal nerve stimulation for gastrointestinal motility disorders and chronic abdominal pain
Abstract
Keywords
Introduction
Invasive vagal nerve stimulation
Noninvasive vagal nerve stimulation
Irritable bowel syndrome
Gastroparesis
Functional dyspepsia
Postoperative ileus
Visceral pain
Summary and future perspectives
References
Chapter 25 Treatment of acute asthma exacerbations with vagus nerve stimulation
Abstract
Keywords
Introduction
Preclinical animal studies
Clinical results
Mechanism of action
Conclusions
References
Chapter 26 Metabolic syndrome: Understanding its root cause, and the role of macrophages and why vagus nerve stimulation may be an effective treatment
Abstract
Keywords
Introduction
The role of macrophages in the maintenance of healthy organ and tissue function
Obesity and the failure of normal efferocytotic mechanisms
Mitochondria, calcium, ROS, and melatonin
Inflammation and mitochondrial dysfunction
The cholinergic antiinflammatory pathway
Type 2 diabetes
NADFLD-NASH
Atherosclerosis
Hypertension
Alzheimer’s disease as type 3 diabetes
Conclusions
References
Chapter 27 Vagus nerve stimulation for the management of obesity, type 2 diabetes mellitus, and metabolic syndrome
Abstract
Keywords
Introduction
Origin, branches, and pathway of vagus
Vagotomy
Vagotomy/vagus nerve blocking/vagus nerve stimulation
Vagus nerve in obesity, type 2 DM, and metabolic syndrome
VNS is beneficial, but how and why?
Vagus transmits messages between liver and brain
Vagus communicates between liver and pancreatic β cells
Vagus also regulates insulin secretion
Role of vagus in obesity, type 2 DM, and metabolic syndrome
Conclusions and future therapeutic implications
References
Chapter 28 Vagus nerve stimulation and kidney function
Abstract
Keywords
Introduction
Acute kidney injury
Chronic kidney disease
End-stage kidney disease
Kidney transplant
Chronic kidney inflammatory disorders
Lupus
Sympathetic overactivity in kidney disease
Conclusions
References
Chapter 29 The neural tourniquet
Abstract
Keywords
Introduction
The inflammatory reflex
Traumatic hemorrhage
Hemorrhage management in clinical medicine
Rationale for enhancing hemostasis
The neural tourniquet
Swine ear hemorrhage
Rodent visceral hemorrhage
Murine tail hemorrhage
Murine hemophilia A
Clinical applications
Conclusions
References
Section VI: Future applications for vagus nerve stimulation
Chapter 30 Vagus nerve stimulation for the treatment of heart failure
Abstract
Keywords
Introduction
Autonomic nervous system modulation in HF
Structural and functional organization of cardiac nervous system
Maladaptive cardiac neuronal hierarchy in HF
Relevance of vagus nerve as a target for HF
Preclinical studies of VNS for HF
Stimulation parameters
Experimental studies of VNS in animal models
Neural fulcrum
Clinical trials of VNS for HF
Avenues for future research
Conclusions
References
Chapter 31 Vagus nerve stimulation for long COVID
Abstract
Keywords
Introduction
The vagus nerve, a strong link to overcome Long COVID
Noninvasive VNS clinical trials in LC are promising
Noninvasive VNS could prevent LC
Conclusion
References
Chapter 32 Vagal nerve stimulation applications in oncology
Abstract
Keywords
Introduction
The vagus nerve
Vagus nerve stimulation
Mechanism of action
Literature review
Other applications outside of tumorigenesis and disease modification
Complications associated with VNS
Conclusion
References
Index

Peter Staats

Peter S. Staats, MD, MBA is a board-certified physician specializing in pain medicine. Currently, Dr. Staats is seeing patients at Premier Pain Centers, a pain management practice with seven locations throughout New Jersey. He has been consistently recognized as one of the country’s foremost pain management doctors. This includes being named one of America’s Top Doctors by U.S. News and World Report for the last decade, noted as being among the top 1% of pain management physicians in the country. He has been acknowledged as one of New Jersey’s Top Doctors from New Jersey Monthly magazine for the past seven years. Dr. Staats was also the recipient of the Outstanding Pain Physician award, a national recognition as selected by his peers in the interventional pain medicine community.Dr. Staats is certified by the National Board of Medical Examiners, the American Board of Pain Medicine, and the American Board of Anesthesiology. He is also a fellow of the World Institute of Pain and the North American Neuromodulation Society. He is the author of over 200 articles, abstracts and chapters regarding pain management, and has written several books on the science of pain medicine.

Affiliations and expertise

Premier Pain Center, Chief Medical Officer, electroCore, Chief Medical Officer, National Spine and Pain Center, New Jersey, USA

Cenk Ayata

Dr. Ayata is a Neurologist and a clinician-scientist dedicated to translational research on neurovascular function and dysfunction. He explores therapies to augment perfusion and oxygenation in acute stroke (e.g., hyperoxia, induced hypertension, Rho-kinase inhibition), the pathophysiological roles of injury depolarizations in stroke, and targeting spreading depression in migraine. Dr. Ayata is expert in non-invasive in vivo investigations of cerebrovascular physiology and pathophysiology in mice under full systemic physiological control. In collaboration with Dr. Joutel, Dr. Ayata defined a novel enhanced CSD-susceptibility phenotype in Notch3R90C mutant mice, providing an explanation for the increased incidence and severity of migraine with aura in CADASIL patients.

Affiliations and expertise

Assistant Professor,Harvard Medical School; Assistant in Neurology and Neuroscience, Massachusetts General Hospital, Boston, MA, USA

Imanuel Lerman

Dr. Lerman is a board-certified neurologist who specializes in pain management. He has extensive experience in ultrasound guidance for interventional pain procedures and interventional headache treatment, teaching and speaking nationally on these subjects. As an assistant professor in the Department of Anesthesiology at UC San Diego School of Medicine, Dr. Lerman carries out numerous clinical trials at UC San Diego Medical Center, the Altman Clinical Trial Research Institute, and the VA San Diego Healthcare System. His clinical reasarch studies primarily focus on understanding the impact of neurotechnologies (e.g. spinal cord stimulation, vagal nerve stimulation, and other central and peripheral nerve stimulation) on pain, learning and mental health disorders.. Dr. Lerman is a founding board member of the American Interventional Headache Society, faculty and founding member of the Regenerative Medicine special interest group within the American Society of Regional Anesthesiology and Pain Medicine, and faculty member for the World Academy of Pain Medicine Ultrasonography.

Affiliations and expertise

Assistant Professor of Anesthesiology, UCSD Center for Pain, La Jolla, CA, USA

Alaa Abd-Elsayed

Dr. Alaa Abd-Elsayed joined the faculty of the Anesthesiology Department at the University of Wisconsin in 2014 to provide Chronic Pain Medicine Services as part of the Interventional Pain Program. He received his medical training at Assiut University Medical School in Egypt, completed a master’s degree in Public Health, research fellowship at Cleveland Clinic, and residency in anesthesiology and pain management fellowship at University of Cincinnati. As part of the Interventional Pain Program, Dr. Abd-Elsayed evaluates patients at the Pain Clinic, and when an interventional pain treatment is appropriate, performs procedures at the Madison Surgery Center. Over the course of his career, he has received numerous research grants, published more than 70 peer-reviewed manuscripts and authored several editorials and book chapters. He has presented at more than 60 international and national conferences and has earned more than 15 awards at the state and national levels. In addition, he has served as a reviewer for more than 20 journals and as an editor to several journals.

Affiliations and expertise

University of Wisconsin, USA

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Vagus Nerve Stimulation

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Innovate. Sustain. Transform.

Institutional subscription on ScienceDirect

Peter Staats

Cenk Ayata

Imanuel Lerman

Alaa Abd-Elsayed

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