Visceral Pain - From Bench to Bedside (May 28, 2024)_(9819991668)_(Springer)

Patients with chronic visceral pain present a challenge for medical providers because of their vague presenting symptoms and frequent lack of identifiable pathology. Despite this, chronic visceral pain can be a debilitating medical condition that increases morbidity and decreases quality of life; the long-term consequences of which cause significant socioeconomic burden and debility. Covering the newest trends, studies, diagnosis and treatments in visceral pain care, as well as the pain treatment strategies that have been successfully employed in the past, this book brings readers fully up to date with effective recognitions and treatments for visceral pain. The clinical evaluation and presentation of common chronic visceral pain conditions and multimodal treatment options that can be used to assist patients and providers are focused. Contents Contributors Editors Associate Editors 1: Introduction 1.1 An Overview of Visceral Pain 1.1.1 Concept of Pain 1.1.2 Classification of Pain 1.2 Concept and Classification of Visceral Pain 1.3 Clinical Features of Visceral Pain 1.3.1 Clinical Visceral Pain 1.3.2 Specific Types of Visceral Pain or Abdominal Pain Syndrome 1.4 Summary References 2: Anatomy of the Visceral Nerves 2.1 Visceral Motor Nerves 2.1.1 Differences Between Visceral Motor Nerves and Somatic Motor Nerves 2.1.2 Sympathetic Nerve Anatomy 2.1.3 Anatomy of Parasympathetic Nerves 2.1.4 Main Differences Between Sympathetic and Parasympathetic Nerves 2.1.5 Visceral Plexus 2.1.6 The Enteric Nervous System 2.2 Visceral Sensory Nerves 2.2.1 Characteristics of Visceral Sensory Nerves 2.2.2 Endoreceptors 2.2.3 Visceral Sensory Nerve Conduction Pathway 2.2.4 Referred Pain References 3: Physiological Mechanisms of Visceral Pain 3.1 Introduction 3.2 Visceral Sensory Nerves 3.3 Physiological Features of Visceral Pain 3.4 Visceral Nociception 3.4.1 Noxious Visceral Stimuli 3.5 Visceral Afferent Fibers 3.5.1 Vagal Afferents 3.5.2 Spinal Afferents 3.6 Mechanisms of Visceral Pain 3.6.1 Peripheral Mechanisms of Visceral Pain Production 3.6.2 Central Processing of Visceral Pain 3.7 Summary References 4: Pathophysiological Mechanisms of Visceral Pain 4.1 Etiology of Visceral Pain 4.1.1 Chest Visceral Pain 4.1.1.1 Respiratory Organ Diseases 4.1.1.2 Circulatory Organ Diseases 4.1.1.3 Esophageal Disease 4.1.1.4 Referred Chest Pain Caused by Abdominal Visceral Pain 4.1.1.5 Others 4.1.2 Abdominal Visceral Pain 4.1.2.1 Pain of Gastrointestinal Diseases 4.1.2.2 Pain in Pancreatic Diseases 4.1.2.3 Pain of Hepatobiliary Diseases 4.1.2.4 Pain of Urinary System Diseases 4.1.2.5 Pain of Retroperitoneal Disease 4.1.2.6 Pain of Vascular Disease 4.1.2.7 Abdominal Pain of Spinal Origin 4.1.2.8 Functional Abdominal Pain Syndrome 4.1.3 Gynecological and Obstetric Internal Pain 4.1.3.1 Labor Pains 4.1.3.2 Dysmenorrhea 4.1.3.3 Supernumerary Ovary 4.1.3.4 Adenomyosis of the Uterus 4.1.3.5 Adhesions 4.1.3.6 Adnexal Cysts 4.1.3.7 Endometriosis 4.1.3.8 Smooth Muscle Tumor 4.1.3.9 Preserved Ovary Syndrome 4.1.3.10 Pelvic Stasis Syndrome 4.1.3.11 Peritoneal Cysts 4.1.3.12 Symptomatic Pelvic Relaxation Disorder 4.1.3.13 Other 4.1.4 Cancer Pain 4.1.4.1 Pain Caused by Cancer Development 4.1.4.2 Pain Caused by Cancer Treatment 4.1.4.3 Cancer Pain Syndrome 4.2 Conduction of Visceral Pain 4.2.1 Visceral Pain Receptors 4.2.1.1 General Concept and Characteristics of Receptors 4.2.1.2 Characteristics of Visceral Pain Receptors 4.2.1.3 Injurious Stimuli and the Transduction of Injurious Receptors 4.2.2 Visceral Pain Afferent to Nerve Fibers 4.2.2.1 Visceral Pain Afferent Fibers 4.2.2.2 Differences Between Visceral Pain Afferent Fibers and Somatic Pain Afferent Fibers 4.2.2.3 Visceral Sensory Nerves 4.2.2.4 Excitability of Visceral Afferent Neurons 4.2.3 Visceral Pain Conduction Pathway 4.2.3.1 Synapse-Mediated Conduction Mechanism 4.2.3.2 Conduction Pathways 4.2.4 Characteristics of the Visceral Pain Centers and Their Information Transmission 4.2.4.1 Subcortical Centers 4.2.4.2 Higher Centers 4.2.4.3 Characteristics of Visceral Information Central Transmission 4.3 Perception and Regulation of Visceral Pain 4.3.1 Feeling Characteristics of Different Organs 4.3.2 Central Sensory Characteristics 4.3.2.1 Performance of Pain Conduction Tracts 4.3.2.2 Performance of Subcortical Centers 4.3.2.3 Performance of Higher Centers 4.3.3 Regulatory Mechanisms of Visceral Pain 4.3.3.1 Feedback Regulation of Receptors 4.3.3.2 Inter-synaptic Inhibition 4.3.3.3 Convergence 4.3.3.4 Multisynaptic Transmission 4.3.4 Modulation of Nociception by the Central Nervous System at All Levels 4.3.4.1 Cortical Modulation 4.3.4.2 Modulation of the Mesencephalon 4.3.4.3 Modulation of the Brainstem 4.3.4.4 Modulation of the Spinal Cord 4.3.5 Nociceptive Hypersensitivity 4.3.5.1 Peripheral and Central Mechanisms of Pain Sensitization 4.3.5.2 Generation of Central Sensitization 4.3.5.3 Primary and Secondary Nociceptive Hypersensitivity 4.3.5.4 Hyperalgesia Due to Psychological Factors 4.4 Pathophysiological Mechanisms of Visceral Pain 4.4.1 Neurophysiological Mechanisms of Visceral Pain 4.4.2 Endogenous Biochemical Mechanisms of Visceral Pain 4.4.3 Psychological Mechanisms of Visceral Pain 4.4.4 Mechanism of Referred Pain 4.4.4.1 Nerve Convergence 4.4.4.2 Convergence-Facilitation 4.4.4.3 Gate Mechanism 4.4.4.4 Convergence-Projection 4.4.4.5 Axonal Reflex Theory References 5: Evaluation and Examination of Visceral Pain 5.1 Introduction 5.2 Assessment of Visceral Pain in Animal Models 5.2.1 Recording of Abdominal Muscle Contraction 5.2.2 Histological Analysis 5.2.3 Electrophysiology of Nerve Bundles or a Neuron 5.2.4 Response of the Model to Drug Disposition 5.3 Assessment of Visceral Pain in Humans 5.3.1 Principles of Pain Assessment 5.3.2 Pain Evaluation Approach 5.3.3 Determination of Location of Pain 5.3.4 Commonly Used Self-Report and Behavioral Analysis Methods for Evaluating Pain Level 5.4 Special Features of Visceral Pain Assessment 5.4.1 True Visceral Pain and Pseudovisceral Pain 5.4.2 Visceral Referred Pain 5.5 Initial Diagnosis of Visceral Pain 5.5.1 Medical History 5.5.2 Physical Examination 5.6 Diagnostic Testing 5.7 Summary References 6: Medication Treatment for Visceral Pain 6.1 Current Status of Pharmacological Treatment of Visceral Pain and Commonly Used Drugs 6.2 Current Medications for Visceral Pain 6.2.1 Opioids 6.2.1.1 κ-Opioid Receptor Drugs 6.2.1.2 μ-Opioid Receptor Class of Drugs 6.2.1.3 κ, μ Double Receptor Drugs: Oxycodone Hydrochloride 6.2.2 Non-opioid Drugs 6.2.2.1 NSAID 6.2.2.2 Beneficial Intestinal Bacteria 6.2.2.3 Corticotropin-Releasing Factor Receptor-1 (CRF1R) Antagonists 6.2.2.4 Pregabalin 6.2.2.5 TRP Ion Channel Orange Resistance Drug 6.3 Combination Therapy 6.4 Summary References 7: Neuromodulation Therapy for Visceral Pain 7.1 Nerve Block or Neurolysis 7.1.1 Abdominal Plexus or Visceral Nerve Block/Neurolysis 7.1.2 Superior Hypogastric Plexus Block 7.1.3 Inferior Hypogastric Plexus Block 7.1.4 Ganglion Impar Block 7.1.5 Intraspinal Infusion 7.2 Neuroelectrical Stimulation Techniques 7.2.1 Gastrointestinal Electrical Stimulation Techniques and Gastrointestinal Tract Movement Disorders 7.2.2 Spinal Cord Stimulation (SCS) 7.2.3 Peripheral Nerve Electrical Stimulation 7.2.4 Transcutaneous Electrical Nerve Stimulation 7.2.5 Non-invasive In Vitro Neuromodulation 7.2.6 Motor Cortex Stimulation 7.2.7 Deep Brain Stimulation 7.2.8 Non-invasive Transcranial Stimulation References 8: Traditional Chinese Medicine for Visceral Pain 8.1 Introduction 8.1.1 Pathogenesis and Etiology of Visceral Pain 8.1.2 Classification of Visceral Pain 8.2 TCM for Visceral Cancer Pain 8.2.1 Perception of Visceral Cancer Pain in TCM 8.2.2 TCM in the Treatment of Visceral Cancer Pain 8.2.2.1 Internal Treatment Methods 8.2.2.2 External Treatment Methods 8.2.2.3 A Combination of Internal and External Treatment Methods 8.2.3 Integration and Complementation of TCM with Western Medicine Treatments 8.2.3.1 Opioid-Induced Constipation 8.2.3.2 Combination of TCM and Three-Step Analgesic Ladder 8.2.3.3 TCM in Three-Step Analgesic Ladder 8.2.3.4 TCM for Cancer Pain Relief 8.2.3.5 TCM with Chemotherapy 8.2.3.6 TCM with Radiotherapy 8.2.4 TCM Five-Element Emotional Therapy in Visceral Pain 8.2.4.1 Music Delighting Emotions 8.2.4.2 Following Desires with Understanding 8.2.4.3 Comfort and Uplift Emotions 8.2.4.4 Providing Comfortable Environment 8.2.4.5 Exchanging Feelings and Experience 8.2.4.6 Elimination of Psychogenic Factors 8.2.4.7 Suggestion Therapy 8.2.4.8 Overcoming One Emotion by Another Emotion 8.2.4.9 Emotion Activation Method 8.3 TCM in Noncancer Visceral Pain 8.3.1 Functional Abdominal Pain Syndrome 8.3.1.1 Spleen and Stomach Weakness Type 8.3.1.2 Liver Depression and Qi Stagnation Type 8.3.1.3 Cold Accumulation and Qi Stagnation Type 8.3.1.4 Indigestion and Heat Accumulation Type 8.3.1.5 Summary 8.3.2 Biliary Colic 8.3.3 Chronic Pancreatitis Pain 8.3.3.1 Treatment Based on Syndrome Differentiation 8.3.3.2 Precautions 8.3.4 Stomach Pain 8.3.5 Irritable Bowel Syndrome 8.3.5.1 External Treatment Methods in TCM Ancient Classics 8.3.5.2 Clinical External Treatment Methods of TCM 8.3.5.3 Summary 8.3.6 Chronic Pelvic Inflammatory Disease 8.3.7 Dysmenorrhea 8.3.7.1 TCM Treatment 8.3.7.2 Acupuncture Therapy 8.3.7.3 Massage Therapy 8.3.7.4 Moxibustion Therapy 8.3.7.5 Acupoint Injection Therapy 8.3.7.6 Auricular Point Pressing Therapy 8.3.7.7 Other Treatments 8.3.7.8 Summary 8.3.8 Testicular Pain 8.3.9 Interstitial Cystitis 8.3.9.1 Etiology and Pathogenesis of Interstitial Cystitis [26] 8.3.9.2 Prescriptions for Treating Interstitial Cystitis 8.3.9.3 Summary 8.3.10 Ulcerative Colitis 8.3.10.1 Etiology and Pathogenesis 8.3.10.2 Treatment Based on Syndrome Differentiation 8.3.10.3 Treatment Methods 8.3.10.4 Summary 8.3.11 Chronic Pelvic Pain Syndrome 8.3.11.1 Etiology and Pathogenesis 8.3.11.2 TCM Internal Treatment 8.3.11.3 TCM External Application 8.3.11.4 Acupuncture 8.3.11.5 TCM Retention Enema 8.3.11.6 Summary 8.3.12 Postoperative Pain 8.3.12.1 Prostate-Related Postoperative Pain 8.3.12.2 TCM External Treatment 8.3.12.3 TCM Internal Treatment 8.4 Summary References 9: Other Treatments for Visceral Pain 9.1 Surgical Treatment 9.1.1 Anterolateral Cordotomy 9.1.2 Dorsal Root Entry Zone Dissection 9.1.3 Anterior Commissurotomy 9.1.4 Posterior Median Spinal Cord Punctal Dissection 9.2 Psychological Treatment 9.2.1 Relaxation Therapy 9.2.2 Biofeedback 9.2.3 Hypnotherapy 9.2.4 Psychological Counseling 9.2.5 Mind–Body Intervention 9.2.6 Multidisciplinary Integrated Therapy References 10: Chest Pain 10.1 Introduction 10.2 Causes of Acute Chest Pain 10.2.1 Myocardial Ischemia (MI) The most common cause of acute chest discomfort is 10.2.2 Pericardial Disease 10.2.3 Vascular Disease 10.2.4 Pulmonary Disease 10.2.5 Gastrointestinal Disorders 10.2.6 Musculoskeletal and Other Causes 10.3 Classifications of Chest Pain 10.3.1 Noncardiac Chest Pain (NCCP) 10.3.1.1 Etiologies of NCCP 10.3.1.2 Evaluation of NCCP 10.3.1.3 Summary 10.3.2 Cardiac Chest Pain 10.4 Clinical Assessment 10.5 Assessment and Diagnostic Testing 10.5.1 Medical History 10.5.2 Physical Examination 10.5.3 Electrocardiography 10.5.4 Chest Radiography 10.5.5 Biomarkers 10.5.6 HEART Score 10.5.7 Conclusion 10.6 Treatments 10.6.1 Acute Coronary Syndrome (ACS) 10.6.2 Pneumothorax (PTX) 10.6.3 Pericardial Tamponade 10.6.4 Aortic Dissection 10.6.5 Esophageal Perforation 10.6.6 Gastrointestinal Reflux Disease (GERD) 10.6.7 Pulmonary Embolism (PE) 10.6.8 Costochondritis 10.6.9 Generalized Anxiety Disorder (GAD) 10.6.10 Cognitive Therapy References 11: Pain in Abdominal Viscera 11.1 Abdominal Pain in Irritable Bowel Syndrome 11.1.1 Definition and Classification of Irritable Bowel Syndrome 11.1.2 The Etiology and Pathogenesis of Abdominal Pain in Irritable Bowel Syndrome 11.1.3 Diagnosis and Treatment of Abdominal Pain and Irritable Bowel Syndrome 1. Diagnosis 2. Treatment (a) Health education (b) Dietary treatment (c) Antispasmodics 11.2 Peptic Gastric Ulcer 11.2.1 Possible Pathogenesis of Peptic Ulcer Pain 11.2.2 Peptic Ulcer Abdominal Pain Site and Characteristics pain is often located in pyloric ulcers are mostly located in duodenal ulcers are mostly located in can be radiated to Ulcer disease pain may present as The intensity of pain is When the ulcer is combined with pyloric obstruction, the abdominal pain may become 11.2.3 Treatment of Peptic Ulcer Pain 11.3 Chronic Pancreatitis and Pain Due to Its Acute Attacks 11.3.1 Definition, Epidemiology, and Classification of Chronic Pancreatitis 11.3.2 Chronic Pancreatitis and Pain 11.3.3 Mechanisms of the Occurrence of Pain in Chronic Pancreatitis 11.3.4 Treatment of Chronic Pancreatitis Pain 11.3.4.1 Medical Treatment 11.3.4.2 Endoscopic Treatment 11.3.4.3 Surgical Treatment 11.3.4.4 Comparative Control Study of Surgical and Endoscopic Treatment 11.4 Biliary Dyskinesia 11.4.1 Overview 11.4.2 Possible Mechanisms of Biliary Dyskinesia 11.4.3 Diagnosis, Examination, and Treatment of Biliary Dyskinesia 11.4.3.1 Diagnosis and Examination of Biliary Dyskinesia 11.4.3.2 Treatment of Functional (Non-stone) Biliary Pain 11.4.4 Diagnosis, Examination, and Treatment of Biliary Dyskinesia After Cholecystectomy 11.4.4.1 Diagnosis and Examination of Biliary Dyskinesia After Cholecystectomy 11.4.4.2 Causes of Functional Biliary Pain After Cholecystectomy 11.4.4.3 Clinical Treatment of Functional Biliary Pain After Cholecystectomy 11.5 Visceral Pain Due to Surgery (Abdominal Adhesions) 11.5.1 Overview 11.5.2 Pathophysiology of Adhesive Pain 11.5.2.1 Pathogenesis of Abdominal Adhesions 11.5.2.2 Factors in the Development of Adhesive Pain 11.5.2.3 Differential Diagnosis of Abdominal Wall Pain 11.5.3 Treatment of Visceral Pain with Abdominal Adhesions 11.5.3.1 Diagnostic Treatment 11.5.3.2 Treatment of Pain Due to Visceral Factors 11.5.3.3 Treatment of Abdominal Wall Pain 11.5.3.4 Other Treatment Methods 11.5.4 Prevention Strategies for Abdominal Adhesions 11.5.4.1 Barrier Prevention and Control 11.5.4.2 Drug Prevention and Control 11.5.5 Summary 11.6 Common Pediatric Recurrent Abdominal Pain 11.6.1 Overview 11.6.2 Etiology, Diagnosis, and Treatment of Organic RAP 11.6.2.1 Etiology 11.6.2.2 Diagnosis and Differential Diagnosis 11.6.2.3 Treatment of Organic RAP 11.6.3 Etiology, Diagnosis, and Treatment of Functional RAP 11.6.3.1 Etiology and Diagnosis 11.6.3.2 Treatment of Functional RAP 11.6.3.3 Prognosis of Functional RAP 11.6.4 Perioperative Abdominal Pain in Children 11.6.5 Summary References 12: Chronic Abdominal Pain Due to Obstetric and Gynecological Factors 12.1 Introduction 12.2 Definition of CPP 12.3 Prevalence of CPP 12.4 Pelvic Anatomy and Pathogenesis of CPP 12.4.1 Pelvic Anatomy 12.4.1.1 Innervation of Female Genital Organs 12.4.1.2 Function of Nerves in Female Genital Organs Sensory Nerve Motor Nerve 12.4.2 Pathogenesis of CPP 12.4.2.1 Common CPP-Related Syndromes Endometriosis Adenomyosis Hydrosalpinx Pelvic Inflammatory Disease (PID) Pelvic Congestion Dysmenorrhea Vulvodynia or Vestibulodynia 12.5 Diagnostic Ideas for CPP in Women 12.5.1 Medical History 12.5.2 Physical Examination 12.5.3 Laboratory Tests and Imaging 12.5.3.1 Laboratory Tests 12.5.3.2 Ultrasound 12.5.3.3 Pelvic Venography 12.5.3.4 Laparoscopy 12.6 Treatments for CPP 12.6.1 Treatments for Endometriosis 12.6.2 Treatment for Dysmenorrhea 12.7 Summary References 13: Visceral Pain and Pelvic Pain Related to Urogenital System 13.1 Introduction 13.2 Definition of Chronic Pelvic Pain 13.3 Mechanisms of CPP 13.3.1 Central Sensitization 13.3.2 Mechanisms of Spinal Cord and Visceral Hyperalgesia 13.3.3 Advanced Central Modulation of Nociceptive Pathways in Spinal Cord 13.3.4 Emotional, Cognitive, Behavioral, and Sexual Response Mechanisms 13.3.4.1 Neuromodulation and Psychology 13.3.4.2 Autonomic Nervous System 13.3.5 Other Mechanisms 13.3.5.1 Endocrine System 13.3.5.2 Genetics and Chronic Pelvic Pain 13.4 Classification of Chronic Pelvic Pain 13.4.1 Guidelines for the Classification of Chronic Pelvic Pain Syndrome 13.4.2 Classification of Common Chronic Pelvic Pain [11] 13.5 Urogenital/Pelvic Pain in Men 13.5.1 Mechanism of Urogenital/Pelvic Pain in Men 13.5.1.1 Innervation and Pelvic Floor Structure of Pelvis 13.5.1.2 Key Role of the Central Nervous System in Persistent Pain 13.5.2 Clinical Manifestations 13.5.2.1 Abnormal Urinary Function 13.5.2.2 Abnormality of Urodynamics 13.5.2.3 Hypersensitivity of Genitourinary System 13.5.3 Treatment 13.6 Common Male Pelvic Pain Syndromes 13.6.1 Primary Prostate Pain Syndrome 13.6.1.1 Pathogenesis Theories of Spastic Pain in Pelvic Floor Muscle Groups Theory of Neurogenic Inflammation Cytokines Theory Mechanism of Referred Pain 13.6.1.2 Clinical Manifestation 13.6.1.3 Diagnosis 13.6.1.4 Differential Diagnosis 13.6.1.5 Treatment 13.6.2 Bladder Pain Syndrome/Interstitial Cystitis 13.6.2.1 Definition and Overview 13.6.2.2 Etiology and Pathophysiology 13.6.2.3 Diagnosis 13.6.2.4 Treatment 13.6.3 Scrotal Pain Syndrome 13.6.3.1 Diagnosis 13.6.3.2 Treatment 13.6.4 Urethral Pain Syndrome References 14: Visceral Cancer Pain 14.1 Causes of Visceral Cancer Pain and its Clinical Manifestations 14.2 Current Treatment of Cancer Pain 14.3 Perineural Infiltration and Visceral Cancer Pain 14.3.1 Perineural Infiltration of Tumors 14.3.2 Molecular Mechanisms of Peripheral Nerve Infiltration 14.3.3 PNI and Pain Production in PDA 14.3.4 Treatment Strategies for PN and Pain 14.4 Pharmacological Treatment of Visceral Cancer Pain 14.4.1 Opioids 14.4.1.1 Routes of Drug Administration 14.4.1.2 Precautions for Clinical Application of Opioids 14.4.2 Nonsteroidal Anti-Inflammatory Drugs 14.4.3 Anticonvulsant Drugs and Antidepressants 14.5 Minimally Invasive Treatment of Visceral Cancer Pain 14.5.1 Nerve Block/Destruction 14.5.1.1 Neurolytic Celiac Plexus Block 14.5.1.2 Superior Hypogastric Plexus Block 14.5.1.3 Ganglion Impar Block 14.5.2 Intrathecal Analgesia 14.5.2.1 Intrathecal Analgesic Drug Treatment 14.6 Summary References 15: New Technologies and Prospects in the Treatment of Visceral Pain 15.1 Progress in Medical Treatment of Visceral Pain 15.1.1 Adjuvant Drug Therapy 15.1.1.1 GABA Analogues 15.1.1.2 Antispasmodics 15.1.1.3 Antidepressants 15.1.2 Unconventional Treatment 15.1.2.1 TRPV1 Receptor Antagonist 15.1.2.2 Ketamine 15.1.2.3 Anti-NGF Monoclonal Antibody 15.1.2.4 Linaclotide 15.1.2.5 Other Unconventional Drugs 15.2 Progress in Nonmedical Treatment of Visceral Pain 15.2.1 Transcranial Direct Current Stimulation 15.2.2 Transcranial Magnetic Stimulation 15.2.3 Transcutaneous Electrical Nerve Stimulation 15.2.4 Neurolysis 15.2.5 Psychological Intervention 15.3 Other Progress in Treatment of Visceral Pain 15.3.1 Dietotherapy 15.3.1.1 Role of Diet Management in IBS Treatment 15.3.1.2 Introduction of Low-FODMAP Diet 15.3.1.3 Mechanisms of Low FODMAP Diet 15.3.1.4 Effectiveness of Low FODMAP Diet Short-Term Clinical Outcome Long-Term Clinical Outcome 15.3.1.5 Potential Risks of Low FODMAP Diet Microbiota in the Gastrointestinal Tract Nutritional Intake 15.3.2 Probiotic Therapy 15.4 Conclusion References