1;Preface;5 2;Contents;5 3;Contributors;5 4;Part I: Role of Sensory Nerves in Disease;13 4.1;Neuropathic Pain: A Clinical Perspective;14 4.1.1;1 Introduction and Definition of Neuropathic Pain;15 4.1.2;2 Classification;16 4.1.3;3 Signs and Symptoms of Neuropathic Pain;19 4.1.4;4 Pathophysiological Mechanisms and Drug Targets in Neuropathic Pain;19 4.1.4.1;4.1 Peripheral Sensitization of Primary Afferents in Animals;21 4.1.4.2;4.2 Peripheral Sensitization of Primary Afferents in Patients;25 4.1.4.3;4.3 Pharmacological Approaches That Modify Peripheral Sensitization of Primary Afferents;27 4.1.4.3.1;4.3.1 Sodium-Channel Blockers;27 4.1.4.3.2;4.3.2 Topically Applied Capsaicin;28 4.1.4.4;4.4 Central Sensitization in the Spinal Cord in Animals;28 4.1.4.5;4.5 Central Sensitization of the Spinal Cord in Patients;29 4.1.4.6;4.6 Pharmacological Approaches That Modify Central Sensitization in the Spinal Cord;30 4.1.4.6.1;4.6.1 Calcium-Channel Modulators;30 4.1.4.6.2;4.6.2 Tramadol and Opioid Analgesics;31 4.1.4.6.3;4.6.3 NMDA-Receptor Antagonists;31 4.1.4.6.4;4.6.4 Cannabinoids;32 4.1.4.7;4.7 Central Descending and Intraspinal Control Systems: Inhibition and Fascilitation in Animals and Patients;32 4.1.4.8;4.8 Pharmacological Approaches That Modify Descending Control Systems;33 4.1.5;5 Treatment Guidelines in Neuropathic Pain;33 4.1.6;6 The Future: Diagnostic Tools To Dissect Individual Mechanisms and To Tailor Individual Treatment;35 4.1.7;7 Conclusion;37 4.1.8;Acknowledgements;37 4.1.9;References;37 4.2;Visceral Pain: The Neurophysiological Mechanism;42 4.2.1;1 Introduction;43 4.2.2;2 Behavioral Studies for Visceral Pain in Laboratory Animals;44 4.2.2.1;2.1 Inflammatory Model;44 4.2.2.2;2.2 Neonatal Maternal-Separation-Induced Stress Model;45 4.2.2.3;2.3 Neonatal Noxious-Stimulus-Induced Visceral Hyperalgesia Model;47 4.2.3;3 Contribution of Sensory Afferents in Visceral Pain;49 4.2.3.1;3.1 Anatomical Distribution of Visceral Afferents;49 4.2.3.2;3.2 Response Characteristics of Visceral Afferents;49 4.2.3.2.1;3.2.1 Visceral Afferents in the Gastrointestinal Tract;50 4.2.3.2.2;3.2.2 Visceral Afferents in the Urinary Tract;52 4.2.3.2.3;3.2.3 Visceral Afferents in the Female Reproductive Organs;60 4.2.3.3;3.3 Sensitization and Cross-Sensitization of Visceral Afferents;61 4.2.3.4;3.4 Pharmacological Modulation of Visceral Afferents and Visceral Pain;64 4.2.3.4.1;3.4.1 kappa-Opioid Receptor;64 4.2.3.4.2;3.4.2 P2X Purine Receptors;65 4.2.3.4.3;3.4.3 5-HT3 and 5-HT4 Seretonin Receptors;65 4.2.3.4.4;3.4.4 N-Methyl-d-aspartate Receptor (NMDAr);67 4.2.3.4.5;3.4.5 Tachykinin Receptors: NK1, NK2, and NK3;68 4.2.3.4.6;3.4.6 Transient Receptor Potential Vanilloid 1;68 4.2.3.4.7;3.4.7 GABAB Receptor;69 4.2.4;4 Conclusion;70 4.2.5;Acknowledgements;71 4.2.6;References;71 4.3;Migraine;86 4.3.1;1 Introduction;87 4.3.2;2 A Subset of Sensory (Nocifensor) Neurons Exerts a Dual Afferent and Efferent Function and Mediates Neurogenic Inflammation;88 4.3.3;3 CGRP, Its Receptor, and Receptor Antagonists;90 4.3.4;4 CGRP Release and CGRP-Mediated Responses;91 4.3.5;5 Sensory Neurons and Migraine;92 4.3.6;6 CGRP Antagonists in Migraine;93 4.3.7;7 Conclusions;95 4.3.8;Acknowledgements;96 4.3.9;References;96 4.4;Afferent Nerve Regulation of Bladder Function in Health and Disease;101 4.4.1;1 Anatomy and Innervation of the Lower Urinary Tract;102 4.4.1.1;1.1 Afferent Nerves;103 4.4.1.2;1.2 Central Afferent Pathways;106 4.4.2;2 Histological and Chemical Properties of Afferent Nerves;108 4.4.3;3 Anatomy and Putative Sensory Functions of the Urothelium;111 4.4.4;4 Properties of Afferent Receptors in the Lower Urinary Tract;113 4.4.4.1;4.1 Sacral Afferents;113 4.4.4.2;4.2 Lumbar Afferents;116 4.4.5;5 Electrophysiological Properties of Afferent Neurons;117 4.4.5.1;5.1 Passive Membrane Properties and Action Potentials;117 4.4.5.2;5.2 Sodium Channels;118 4.4.5.3;5.3 Potassium Channels;118 4.4.5.4;5.4 Calcium Channels;119 4.4.5.5;5.5 Purinergic Channels;120 4.4.5.6;5.6 Transi