Visceral Pain

Preface
Contents
In Vivo Non-linear Optical Microscopy as a Multidimensional Approach to Decipher Sensory Coding
1 Introduction
2 Sensory Encoding Theories
3 Use of Optical Approach to Study Sensory Coding
4 Polymodal and Combinatorial Coding in Primary Sensory Neurons
5 Rich Population-Level Coding by Primary Sensory Neurons for Thermosensation
5.1 Sensory Neurons Use Different Coding Strategies for Heat and Cold
5.2 Absolute Versus Relative Temperature Sensing
6 Future Perspectives
References
An Open Science Model to Accelerate the Generation, Implementation and Distribution of Optogenetics and Viral Tools
1 Introduction
2 Development of New Tools
3 Validation and Characterisation of Existing Tools
4 Standard Requirements and Funding Model
5 Conclusion
References
Vagal Neuroinflammation Accompanying Respiratory Viral Infection: An Overview of Mechanisms and Possible Clinical Significance
1 An Overview of the Neurobiology of Airway Sensation
2 Pathogenesis of Respiratory Viruses
3 Neurotropism of Respiratory Viruses
4 Evidence for Viral-Mediated Neuroinflammation
4.1 Impact of Respiratory Viral Infection on Vagal Sensory Neurons
4.2 Impact of Respiratory Viral Infection on Vagal Sensory Pathways in the Brain
5 The Clinical Significance of Respiratory Viral-Induced Neuropathy
References
Stress-Induced Visceral Analgesia: Concept and Pathways
1 Introduction
2 Stress and Pain Modulation: Analgesia Versus Hyperalgesia
3 Is Stress-Induced Analgesia Occurring in Visceral Pain?
4 Roles of Preconditions in the Expression of SIVA
5 Role of Descending Inhibitory Pathways in SIVA
6 Influence of Sex on SIVA
7 Conclusion and Future Considerations
8 Clinical Relevance to DGBIs
References
Evidence of Early Life Stress Exposure and Epigenetic Modifications in Functional Chronic Pain Disorders
1 Introduction
2 Epigenetic Modifications
3 Causes of Epigenetic Modifications
3.1 Early Life Stress
3.2 Environmental
3.3 Heritability
4 Evidence of Epigenetic Mechanisms in Functional Pain Syndromes
4.1 Irritable Bowel Syndrome
4.2 Fibromyalgia
4.3 Headache
5 Conclusion and Future Directions
References
Epigenetic Regulation of Stress-Induced Visceral Pain
1 Introduction
2 Stress and Chronic Pain in IBS
3 Epigenetic Changes in the CeA of Animals Exposed to ELS and WAS
4 Two Epigenetic Mechanisms, One Outcome?
5 Stress-Induced Epigenetic Mechanisms Outside the CeA and Abdominal Hypersensitivity
6 Conclusion
References
The Biomechanics of Distal Colon and Rectum and Its Relevance to Visceral Pain
1 Psychophysical and Neurophysiological Evidence Suggesting the “Mechanical” Nature of Visceral Pain
1.1 The Unique Clinical Characteristics of Visceral Pain
1.2 Mechanical Distension of Distal Colon and Rectum (Colorectum) Drives Visceral Pain
1.3 The Colorectum Is Innervated Predominantly by Mechanosensitive Afferents
2 Methods for Characterizing Colorectal Biomechanics
2.1 Macroscopic Mechanical Tests
2.2 Microscopic Imaging of Collagen Fibers
2.3 Computational Modeling with Nonlinear and Anisotropic Constitutive Equations
3 The Biomechanical Heterogeneity of the Colorectum
3.1 The Anatomy and Function of Layers of the Colorectum
3.1.1 Mucosa
3.1.2 Submucosa
3.1.3 Muscularis Propria
3.1.4 Serosa
3.2 Biomechanical Heterogeneity in the Axial Direction
3.3 Biomechanical Heterogeneity in the Radial (Through-Thickness) Direction
3.4 Biomechanical Heterogeneity in the Circumferential Direction
3.5 In-Plane Biomechanical Heterogeneity
4 Altered Colorectal Biomechanics in Lower GI Disorders
5 Summary and Conclusions
References
Visceral Nociception in Gastrointestinal Disease
1 Visceral Nociception in Gastrointestinal Disease
2 Pain Signalling from the Gut
2.1 IBS Biopsy Supernatants as a Disease-Relevant Noxious Stimulus
3 NaV1.9 as a Target for the Treatment of Pain in IBS-D
4 Matrix Metalloproteinase 12 (MMP12) as a Mediator of Visceral Nociception in IBD Patients
5 Interactome Analysis of Transcriptomic Data from Sensory Neurons and IBD Biopsies
6 Summary
References
Epithelial-Neuronal Communication in Visceral Pain
1 Introduction
2 Heterogeneity of Colonic Epithelial Cells
3 The Role of Enteroendocrine Cells in Visceral Pain
4 Chemical Mediators of Colonic Epithelial-Neuronal Communication
4.1 Adenosine Triphosphate (ATP)
4.2 Serotonin (5-HT)
4.3 Proteases
4.4 Cyclic Guanosine-3′,5′-Monophosphate (cGMP)
5 Optogenetic Investigation of Colonic Epithelial-Neuronal Communication
6 Conclusions and Future Directions
Bibliography
Physiological Mechanisms Underpinning Heightened Perception of Visceral Afferent Signalling in Irritable Bowel Syndrome
1 Context
1.1 Heightened Interoceptive Awareness
1.2 Functional Bowel Disorders
1.3 Central Pain Amplification
1.4 Activation of the Stress Axis
2 Sensitisation of Primary Afferents by Peripheral Factors
2.1 Corticotropin-Releasing Factor (CRF)
2.2 Glucagon-like Peptide-1 (GLP-1)
2.3 Serotonin
2.4 Menstrual Cycle Hormones
3 Inflammatory Factors
4 Summary and Conclusions
References
Untitled
A Fentanyl Analogue That Activates u-Opioid Receptors in Acidified Tissues Inhibits Colitis Pain without Opioid Side Effects
1 Introduction
2 Pain Mechanisms and Visceral Sensory Pathways
3 Challenges of Conventional Opioid Drugs
4 Pharmacodynamic Properties of NFEPP
5 In Vitro Studies of NFEPP in Acidified and Physiologic Conditions
6 NFEPP Inhibits Nociception in Preclinical Inflammatory Pain and Cancer Models
7 On-Target Side Effects of NFEPP and Fentanyl
8 Repeated Applications of NFEPP During the Evolution of Inflammation
9 Conclusion and Future Directions
References
Signalling in the Gut
1 General Considerations on Extrinsic Intestinal Sensing
2 Intestinal Sensing of Pathogenic Bacteria
3 Conclusion
References
Translating Colonic Sensory Afferent Peripheral Mechanosensitivity into the Spinal Cord Dorsal Horn
1 Introduction
2 Peripheral-Encoded Colonic Mechanosensitivity
3 Organisation of Colonic Afferent Input in the Spinal Cord
3.1 Horseradish Peroxidase (HRP) Retrograde Tracing from Splanchnic and Pelvic Afferent Nerve Trunks
3.2 Cholera Toxin Subunit B (CTB) Retrograde Tracing from the Colon Wall
3.3 Trans-neuronal Viral Tracing from the Colon Wall
4 Spinal Cord Dorsal Horn Circuits Receiving and Processing Colonic Afferent Input
4.1 Insights into Dorsal Horn Circuits Processing CRD from Neuronal Activation Distribution Mapping
4.2 Insights into Dorsal Horn Circuits Processing CRD from In Vivo Neuron Response Profiling
4.3 Distribution and Types of Projection Neurons Relaying Colonic Nociceptive Signalling into the Brain
4.4 Interneuronal Circuits Influencing Colonic Nociceptive Signalling into the Brain
5 Relevance of Characterising Spinal Cord Processing to the Management of Chronic Visceral Pain
5.1 Spinal Mechanisms of Colitis-Induced Visceral Pain
6 Conclusion
References
Mechanisms of Spinal Cord Plasticity in Rodent Models of Acute and Post-Colitis Visceral Hypersensitivity
1 Introduction
2 Colitis Induces Peripheral and Spinal Hypersensitivity
2.1 Rodent Models of Colitis
2.2 Peripheral Hypersensitivity
2.3 Spinal Hypersensitivity
3 Plasticity in the Spinal Cord Mediating Colitis-Induced Spinal Sensitisation
3.1 Activity-Driven Plasticity
3.2 Neuroinflammation
3.3 Structural Plasticity
3.4 Synaptic Plasticity
4 Spinal Sensitisation Contribution to Altered Nociceptive Signalling to the Brain
5 Concluding Remarks
References
Neuron-Microglia Dynamic Duo in Chronic Abdominal Pain
1 Introduction
2 Visceral Pain Circuits
3 Visceral Sensitization
4 Spinal Glial Cells in VHS
4.1 Microglia Activation in VHS
4.2 Astrocyte Activation in VHS
5 Conclusion and Future Perspectives
References
Pre-clinical Models of Endometriosis: A Focus on Chronic Pain
1 Introduction
2 Animal Models of Endometriosis
2.1 Non-human Primates
2.2 Rodent
3 Pain Assessment in Animal Models
3.1 Evoked Responses
3.2 Spontaneous Responses
4 Shifting the Paradigm of Isolated Behavioural Analysis to Study Widespread Pain Development in Endometriosis
5 Clinically Relevant Animal Models of Endometriosis for the Study of CPP: A Present Challenge
6 Closing Remarks
References
Spinal Afferent Innervation of the Uterus
1 Introduction
2 Central Origins and Distribution of Spinal Afferents Innervating the Uterus
3 Morphological Characteristics of Uterine-Projecting Spinal Afferent Neurons
3.1 Spinal Afferent Axons
3.2 Spinal Afferent Endings
4 Adaptations of Uterine Afferents to Changes in Reproductive Status
4.1 Puberty and the Reproductive Cycle
4.2 Pregnancy and Parturition
5 Concluding Remarks
References
Post-Infectious Bladder Hypersensitivity in the Development of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)
1 Introduction
2 Epidemiology and Clinical Significance of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)
3 Bladder Sensation in Health and IC/BPS
4 Mechanisms Underlying Afferent Hypersensitivity in IC/BPS
4.1 Urothelial Permeability
4.2 Bladder Inflammation
5 Urinary Tract Infections
5.1 Evidence for UTIs in the Pathogenesis of IC/BPS
5.2 Potential Mechanisms Underlying IC/BPS Following UTI
5.2.1 UTI Initiates a Cycle of Bladder Permeability and Inflammation
5.2.2 UTI-Induced Neuroplasticity of Bladder Afferent Pathways
6 Conclusions
References
Index