Functional Dyspepsia (eBook)

Kazunari Tominaga, Osaka Medical College, Second Department of Internal Medicine, Takatsuki, JapanHiroaki Kusunoki, Kawasaki Medical School, Department of General Medicine, Kurashiki, Japan

Preface 5
Contents 7
Part I: Etiology 9
Chapter 1: Definition and Prevalence 10
1.1 Definition 10
1.1.1 Background and History 10
1.1.2 Uninvestigated and Investigated Dyspepsia 11
1.1.3 Subgroups 13
1.1.4 Update from Rome III to Rome IV 13
1.2 Epidemiology 14
1.3 Overlap 14
1.3.1 EPS and PDS 14
1.3.2 GERD and FD 15
1.3.3 IBS and FD 16
1.4 Pediatric FD 16
1.5 Limitation of Rome IV 17
References 18
Chapter 2: Genetic Factor 22
2.1 Introduction 22
2.2 Familial Accumulation of FD 23
2.3 The Genotype of GNB3 and FD 24
2.4 FD Clarified by Genetic Association Study in Japan 25
2.5 Conclusions 28
References 28
Chapter 3: Environmental Factors 31
3.1 Introduction 31
3.2 Food and Dyspepsia 32
3.3 Gastrointestinal Infection and Dyspepsia 33
3.4 Acute and Chronic Stress and Dyspepsia 34
3.5 Abuse as an Early-Life Stress 35
3.6 Animal Models for Functional Dyspepsia 36
3.7 Duodenal Inflammation as a Key Mechanism 36
3.8 Summary and Outlook 37
References 38
Part II: Pathophysiology 43
Chapter 4: Neuro-gastroenterology: Central and Autonomic Nervous System 44
4.1 Association of Various Stimuli from Gastrointestinal Tracts with Central Sensation and Abdominal Symptoms in FD 45
4.1.1 Gastric Acid (Chemical Stimulation) 45
4.1.2 Gastric Distension (Mechanical Stimulation) 46
4.2 Association of the CNS with Pathophysiology of FD 47
4.2.1 Regional Activity 48
4.2.2 Serotonin (5-HT) Pathway 48
4.3 Association of Autonomic Nervous System (ANS) with Pathophysiology of Functional Dyspepsia 50
4.4 Therapeutic Possibility for FD via the Neurological Pathway 52
4.4.1 Conclusions 52
References 52
Chapter 5: Neuro-gastroenterology: Enteric Nervous System 55
5.1 Enteric Nervous System 55
5.2 Enteric Glial Cells (EGCs) 56
5.3 Enteric Glial Cells and Functional Gastrointestinal Disorders 58
5.4 Conclusions 60
References 61
Chapter 6: Neuro-gastroenterology: Esophagogastric Function (Motility) 63
6.1 Basic Esophageal Motor Function 63
6.1.1 Upper Esophageal Sphincter (UES) 64
6.1.2 Primary Peristaltic Contraction 64
6.1.3 Secondary Peristaltic Contraction 65
6.1.4 Lower Esophageal Sphincter (LES) 65
6.2 Functional Esophageal Diseases 66
6.2.1 Gastroesophageal Reflux Disease (GERD) 66
6.2.2 Esophageal Motility Disorders 67
6.3 The Relationship Between Functional Dyspepsia (FD) and Functional Esophageal Diseases 68
6.3.1 Commonality Between FD and GERD 68
6.3.2 Involvement of the Nitroxidergic Nerve with the Esophagus and Stomach 69
6.4 Differentiating FD and Functional Esophageal Diseases 69
6.4.1 Difficulty in Differentiating Between FD and GERD 69
6.4.2 Limitations in Clinical Symptoms and Diagnosis 70
6.5 Future Considerations 70
References 71
Chapter 7: Neuro-gastroenterology: Gastroduodenal Function (Motility) and Ultrasonographic Assessment 72
7.1 Gastrointestinal Motility Disorders 73
7.1.1 Test Meal (Consommé Soup) 79
7.2 Parameters 80
7.2.1 Fasting Antral Area (FAA) 80
7.2.2 Gastric Accommodation Reflex (GAR) 81
7.2.3 Gastric Emptying (Gastric Emptying Rate: GER) 81
7.2.4 Antral Contractions (Motility Index: MI) 82
7.2.5 Duodenogastric Reflux (DGR) 82
7.3 US Methods 85
7.3.1 Pharmacometrics 89
7.3.1.1 Acotiamide 90
7.3.1.2 Rikkunshito 91
References 92
Chapter 8: Ghrelin and Functional Dyspepsia 94
8.1 Introduction 95
8.2 Ghrelin 95
8.2.1 Ghrelin Action 95
8.2.2 Ghrelin and FD 98
8.2.3 Ghrelin and Stress-Related Hormones 99
8.2.4 Summary 104
References 104
Chapter 9: Psycho-gastroenterology 107
9.1 Introduction 107
9.2 Epidemiology 108
9.2.1 Psychiatric Comorbidity: Anxiety and Depression 108
9.2.2 Personality: Neuroticism, Perfectionism, and Alexithymia 108
9.2.3 Anxiety and Depression: Predictors of Onset of Functional Dyspepsia 109
9.3 Quality of Life: Physical and Mental 109
9.4 Gut–Brain Pathophysiology 110
9.5 Brain Imaging Studies in Functional Dyspepsia 110
9.5.1 Gastric Hypersensitivity and Anxiety in Brain Function 110
9.5.2 Abnormal Brain Connectivity 111
9.5.3 Abuse History and Brain Function 111
9.5.4 Resting-State Positron-Emission Tomography 112
9.5.5 Brain Function and Functional Dyspepsia with and Without Comorbid Anxiety and Depression 112
9.6 Treatment 112
9.6.1 Placebo 112
9.6.2 Antidepressants 113
9.6.3 Psychological Therapy 114
9.7 Conclusions 114
References 114
Chapter 10: Visceral Hypersensitivity Through Transient Receptor Potential Vanilloid 1 Channels (TRPV1) in Functional Dyspepsia 118
10.1 Introduction 119
10.2 Visceral Pain Induced by Mucosal Inflammation 120
10.3 Transient Receptor Potential (TRP) Channels 120
10.4 TRPV1 121
10.4.1 Physiological Role of TRPV1 121
10.4.2 Inflammatory Bowel Disease Is Associated with Upregulation of TRPV1 in Nerve Fibers of the Colon 124
10.5 Nerve Growth Factor (NGF) and Visceral Hypersensitivity 124
10.6 Conclusion 125
References 126
Part III: Treatment 128
Chapter 11: Efficacy of Acid Suppression Therapy 129
11.1 Background 129
11.2 Cochrane Meta-Analysis (H2RAs and PPIs) 131
11.2.1 H2RA 131
11.2.1.1 H2RA Versus Placebo 131
11.2.1.2 Adverse Events 132
11.2.2 PPI 132
11.2.2.1 PPI Versus Placebo 132
11.2.2.2 Adverse Events 133
11.2.2.3 The Effect of PPIs on Individual Dyspepsia Symptoms 133
11.2.2.4 FD and PPI Metabolism 133
11.2.2.5 Geographical Location 133
11.2.3 H2RA Versus PPI 134
11.3 Antacids and Mucosal Protection 134
11.4 FD and H. pylori Infection 134
11.4.1 FD and H. pylori Eradication Therapy 134
11.4.2 Acid Secretion Inhibitory Drugs and H. pylori Status 135
11.5 Conclusion 135
References 135
Chapter 12: Prokinetics 139
12.1 Introduction 140
12.2 Gastrointestinal Motility and FD 141
12.3 Use of Prokinetics as FD Therapeutic Agents 141
12.4 Usefulness of Acotiamide for Treating FD 142
12.5 Conclusions 144
References 145
Chapter 13: Herbal Medicine 146
13.1 Introduction 147
13.2 Rikkunshito 147
13.3 Hange-koboku-to 149
13.4 Other Agents 149
13.5 Precautions When Using Chinese Herbal Medicines 150
13.6 Conclusion 150
References 150
Part IV: Recent Special Topics: Future Treatment Possibility 152
Chapter 14: Gut Dysbiosis and Its Treatment in Patients with Functional Dyspepsia 153
14.1 Introduction 153
14.2 Postinfectious FD 154
14.3 Gastric Dysbiosis in FD 155
14.4 Duodenal Inflammation and Dysbiosis in FD 156
14.5 Mucosa-Associated Microbiota (MAM) in FD 157
14.6 Treatment for Gut Dysbiosis in FD 159
14.7 Conclusion 161
References 161
Chapter 15: Visceral Hypersensitivity in Functional Dyspepsia (FD): Therapeutic Approaches to FD Based on Suppression of Visceral Hypersensitivity 165
15.1 Pathophysiology of FD in FGID 166
15.2 Visceral Hypersensitivity as One of the Pathophysiologies of FD 166
15.3 Assessment of Visceral Hypersensitivity in FD 167
15.4 Mechanisms of Visceral Hypersensitivity 167
15.5 Foods and Lipids Affecting Visceral Hypersensitivity 168
15.6 Psychosocial Factors Affecting Visceral Hypersensitivity 169
15.7 Therapeutics in FD Based on Suppression of Visceral Hypersensitization 169
15.7.1 Drugs for the Improvement of PDS and EPS in FD 170
15.7.2 Drugs Affecting CNS for Reducing Visceral Hypersensitivity 170
15.7.3 Herbal Medicines 170
15.7.3.1 STW5 (Iberogast®) for the Treatment of FD 170
15.7.3.2 Korean Herbal Medicines for the Treatment of FD 171
15.7.3.3 Japanese Kampo Medicine for the Treatment of FD 171
15.8 Conclusion 172
References 173
Chapter 16: Pancreatic Exocrine Function 176
16.1 Type of Upper Abdominal Symptoms and the Abdominal Region of Symptom Feeling 176
16.1.1 Prevalence Rate of the Common Symptoms and Perception Site of the Abdominal Regions 177
16.1.2 Abdominal Symptoms at the Upper and Lower Epigastrium 180
16.2 Pathogenesis of FD in the Digestive Process 180
16.3 Pancreatic Exocrine Function 181
16.4 Conclusions 183
References 184