Nociceptive Membrane (eBook)
496 Seiten
Elsevier Science (Verlag)
978-0-08-046362-9 (ISBN)
Membranes are essential cellular organelles. They not only define cells and other organelles, but also are critical in the cell function by selectively regulating the passage of molecules by acting as a matrix for other signaling molecules, and as conduits of information transfer between the external environment and the cell interior. This series was originally added in 1970 and has since provided a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. Each volume is a guest edited compendium of membrane biology. This series has been a mainstay for practicing scientists and students interested in this critical field of biology. Articles covered in the volume include History of Ion Channels in the Pain Sensory System; Historical Overview; TRPV1, a Polymodal Sensor in the Nociceptor Terminal; Nociceptive Signals to TRPV1 and its Clinical Potential; Gating, Sensitization and Desensitization of TRPV1; TRP Channels as Thermosensors; ASIC Channels; P2X Receptors in Sensory Neurons; Voltage-Gated Sodium Channels and Neuropathic Pain; Voltage-Gated Potassium Channels in Sensory Neurons.
Cover Page 1
Contents 6
Contributors 12
Foreword 16
Previous Volumes in Series 18
Chapter 1: Historical Evolution of Pain Concepts 21
I. Overview 21
II. Pain: A Function of Brain Matter in the 17th Century 22
III. Physics and Pseudophysics in Pain Treatment of the 18th Century 24
IV. Discoveries in the 19th Century Relating to Pain 27
A. Psychophysics of Experimental Pain 27
B. The Discovery of Ether Anesthesia 28
C. The Discovery of Local Anesthesia 30
D. Isolation and Synthesis of Analgesic Substances 31
V. Challenges and Changing Pain Concepts During the 20th Century 34
A. Clinical Research on Pain 34
B. Experimental and Clinical Neurophysiology of Pain 36
C. New Vistas on Pain Since 1950 37
References 38
Chapter 2: History of Ion Channels in the Pain Sensory System 41
I. Introduction 42
II. The TRPV1/VR1 Capsaicin Receptor 43
A. Discovery of Capsaicin Desensitization 43
B. Prediction of the Capsaicin Receptor on C-Polymodal Nociceptors 45
C. Mechanism of Sensory Blockade Induced by TRPV1 Agonists 54
D. Discovery of the Capsaicin-Gated Cation Channel 57
III. Voltage-Gated Na+ Channels 58
A. Summary of Early Observations on Voltage-Gated Na+ Currents in Primary Afferent Neurons 58
B. Identification and Characterization of Na+ Channels in Primary Afferent Neurons 60
C. Alterations in Expression and Function of Na+ Channels in DRG Neurons Under Neuropathic Conditions 64
D. Influence of Neurotrophic Factors on Na+ Channel Expression and Na+ Currents in DRG Neurons 68
E. Effect of Inflammatory Mediators and Conditions on Expression and Function of Na+ Channels in Primary Sensory Neurons 69
IV. Nicotinic Acetylcholine Receptors 71
V. Serotonin Ionotropic Receptor 72
VI. Glutamate Ionotropic Receptors, Proton-Gated Ion Channels (ASIC2, ASIC3), and P2X Purinoceptors 73
A. NMDA, AMPA, and Kainate Glutamate Receptors 73
B. Proton-Gated Ion Channels 74
C. P2X Receptors 74
VII. Initiation of Impulses at Nociceptors 75
References 79
Chapter 3: The Nociceptive Membrane: Historical Overview 93
I. Introduction 93
A. Nociceptors 93
B. Morphology of Nociceptors 95
C. Peripheral Sensitization of Nociceptors 96
D. Transduction Molecules and Ion Channels in Nociceptors 96
II. Nociceptive Transduction 97
A. Transduction of Noxious Mechanical Stimuli 99
B. Transduction of Acidic Stimuli 101
C. Transduction of Noxious Thermal and Chemical Stimuli 102
D. Itch Sensation 114
III. Sensitization of Nociceptors 114
A. Growth Factors 115
B. Noxious Stimuli 115
C. Signal Transduction Pathways 116
IV. Role of Voltage-Gated Sodium and Potassium Channels in Peripheral Sensitization 117
A. Voltage-Gated Sodium Channels 117
B. Voltage-Gated Potassium Channels 118
References 119
Chapter 4: TRPV1: A Polymodal Sensor in the Nociceptor Terminal 133
I. Discovery and Cloning of the Vanilloid Receptor 134
A. Study of Pungent Peppers Leads to Characterization of a "Vanilloid" Receptor 134
B. Molecular Cloning of a Vanilloid Receptor, TRPV1 137
II. TRPV1 Exhibits a Highly Specific Expression Pattern 139
III. Activators and Inhibitors of TRPV1 140
A. Diverse Chemical Activators of TRPV1 140
B. Chemical Antagonists of TRPV1 142
C. TRPV1 is the First Heat-Gated Ion Channel to be Identified 143
D. Structure-Function Relationships for Agonist/Antagonist Interaction with TRPV1 145
IV. Regulation of TRPV1 147
A. TRPV1 Desensitization 148
B. TRPV1 Sensitization 151
C. Convergence of Sensitizing and Desensitizing Influences on TRPV1 154
V. Contributions of TRPV1 to Acute Nociception and Hyperalgesia 154
A. Endogenous TRPV1 and the Detection of Vanilloid Compounds by Nociceptors 155
B. Endogenous TRPV1 and the Detection of Protons by Nociceptors 155
C. Endogenous TRPV1 and Nociceptor Responses to Heat 157
D. TRPV1 and Thermal Hyperalgesia Following Inflammation 159
E. TRPV1 and Thermal Hyperalgesia Following Nerve Injury 161
F. Role for TRPV1 in Mechanical Nociception and Mechanical Hyperalgesia 161
VI. Concluding Remarks 162
References 162
Chapter 5: Nociceptive Signals to TRPV1 and its Clinical Potential 171
I. Introduction 172
A. Effect of Capsaicin on Sensory Neurons 172
B. Biophysical Properties of Capsaicin-Activated Channels 174
C. TRPV1: A Cloned Capsaicin-Activated Channel 175
D. Capsaicin Binds TRPV1 from the Cytosolic Side 175
II. Endogenous Activators of TRPV1 176
A. Anandamide 176
B. N-Arachidonyl-Dopamine 177
C. Metabolic Products of Lipoxygenase 178
D. Binding Capacity of 12-HPETE to TRPV1 178
E. Comparison of 3D Structures of Capsaicin with 12-HPETE 179
III. The TRPV1 Ligand-Binding Sites 181
A. Transmembrane Domain 3 (TM3) Region 181
B. Ligand-Binding Sites in the N- and C-termini 183
IV. Nociceptive Signals to TRPV1 184
A. Bradykinin Signaling Pathway to TRPV1 184
B. 20-HETE Action on TRPV1 186
C. Histamine Intracellular Signals in Sensory Neurons 187
V. TRPV1 Antagonists: A New Class of Analgesics 189
A. Capsazepine 189
B. SC0030 190
C. Iodo-Resiniferatoxin 191
D. High-Throughput Screening for TRPV1 Antagonists 191
E. SB-366791, AMG9810, and their Analogs 192
F. BCTC and its Analogs 192
References 194
Chapter 6: Gating, Sensitization, and Desensitization of TRPV1 201
I. Overview 201
II. Introduction 202
III. Gating Properties of TRPV1 203
A. Capsaicin Action 203
B. Proton Action 205
C. Heat Activation 206
D. Voltage- and Time-Dependent Properties 206
E. Permeability 207
IV. Sensitization of TRPV1 207
A. Phosphorylation by PKA 207
B. Phosphorylation by PKC 208
C. Sensitization by Other Mechanisms 210
V. Desensitization of TRPV1 211
A. Physiological Significance of Desensitization 211
B. Calmodulin-Mediated Desensitization 212
C. Modulation by Lipids 213
VI. Conclusions 213
References 214
Chapter 7: TRP Channels as Thermosensors 219
I. Overview 220
II. Introduction 220
A. General Features of TRP Channels 221
III. TRPV1 is a Noxious Heat Sensor 222
A. Heat Responses in DRG Neurons 222
B. Chemical Activators of TRPV1 223
C. Structure-Function Studies on TRPV1 224
D. Biochemical Regulation 225
E. TRPV1 in Inflammation 226
F. Lessons from "Knockout" Mice 227
G. Effects of TRPV1 Antagonists 228
H. Regulation of TRPV1 Expression 229
I. TRPV1 Expression in Other Neuronal and Non-Neuronal Cells 229
IV. TRPV2 230
A. Expression Pattern 231
B. Other Activators of TRPV2 232
V. TRPV3 and TRPV4 act as Warm Receptors 232
A. TRPV3 233
B. TRPV4 235
C. The Roles of TRPV3 and TRPV4 in Warm Responses of Native Cells 240
VI. Cold Activated Ion Channels 242
A. TRPM8 is Activated by Cool Temperatures and Menthol 243
B. TRPA1 as a Noxious Cold Receptor 246
C. Cold Hyperalgesia 247
VII. TRP Channels as Invertebrate Thermosensors 248
VIII. Conclusions 249
References 249
Chapter 8: Acid Sensing Ionic Channels 261
I. Overview 262
II. Introduction 262
III. Native Proton-Gated Cation Channels in Sensory Neurons 263
IV. Cloned ASICs 265
V. Properties of Cloned ASICs 267
A. Homomeric ASICs 267
B. Heteromultimeric ASICs 271
C. Pharmacology of ASICs 273
D. Modulators of ASICs 275
VI. ASIC Transcripts, Protein, and Currents in Sensory Neurons 279
A. ASIC Transcripts 279
B. ASIC Immunoreactivity 280
C. Native ASIC-Like Currents Characterized in Sensory Neurons 280
VII. Role of ASICs in Nociception 281
A. Do ASICs Meet the Requirements for an Acid Sensor in Pain Perception? 281
B. Evidence for a Role of ASICs in Acid-Induced Pain Perception and Hyperalgesia 283
C. ASICs and Mechanosensation 285
D. ASICs in Spinal Cord 287
VIII. Conclusions 287
A. ASICs and Mechanosensation 287
B. ASICs and Acid Sensing 288
C. Multiple Pathways for Acid and Mechanosensing Might Coexist 289
References 290
Chapter 9: P2X Receptors in Sensory Neurons 297
I. Overview 297
II. Introduction 298
III. Molecular Structure and Pharmacological Profiles of P2X Receptors 299
IV. Electrophysiological Responses Following the Activation of P2X Receptors in Sensory Neurons 301
V. Distribution of P2X Receptors in Sensory Neurons 304
VI. P2X Receptors at Central and Peripheral Terminals 306
VII. Activating P2X Receptors Causes and Modulates Pain Sensation 309
VIII. Persistent Peripheral Inflammation Enhances P2X.Receptor Expression and their Function, thereby Causing Pain 311
IX. P2X Receptors in Sensory Neurons Have Crucial Roles in Neuropathic Pain 314
X. P2X4 Receptors in Spinal Microglia are Essential for Neuropathic Pain 319
XI. Concluding Remarks 320
References 321
Chapter 10: Voltage-Gated Sodium Channels and Neuropathic Pain 331
I. Overview 331
II. Introduction 332
III. The Structure of VGSCs 333
IV. Subtypes of VGSCs and Sodium Currents in Sensory.Neurons 333
V. TTXs VGSCs are Important for Ectopic Discharges and Neuropathic Pain 335
VI. NAv1.3 VGSC May be the Critical Subtype for Ectopic Discharge Generation 335
VII. The Involvement of TTXr VGSCs in Neuropathic Pain 337
VIII. Conclusions 338
References 339
Chapter 11: Voltage-Gated Potassium Channels in Sensory Neurons 343
I. Overview 343
II. Introduction 344
III. Nociceptor Excitability 346
IV. Basics of Kv Channels 346
V. Classes of Native Kv Currents 347
VI. Native Kv Channels in Nociceptive Neurons 349
VII. Changes in Kv Currents and Pain 353
VIII. Kv Channel Gene Expression in Sensory Neurons 355
IX. Analyses of Kv Channel Protein Expression in Nociceptive Neurons 357
X. Kv1 Channel Subunits and Subunit Combinations Define Distinct Populations of Sensory Neurons 360
XI. Kv Channel Localization in Sensory Neurons 363
XII. Kv Channels and Nerve Injury 364
XIII. Genetic Intervention in Kv Channel Expression 365
XIV. Conclusions 366
References 367
Chapter 12: Two-Pore Domain Potassium Channels in Sensory Transduction 373
I. Overview 373
II. Introduction 374
III. K2P Channel Family 375
A. General Properties 375
B. Properties of K2P Channel Subfamilies 375
C. Single Channel Properties of K2P Channels 379
IV. Expression of K2P Channels in Sensory Neurons 381
V. Functional Properties of K2P Channels 381
A. K2P Channels are Active Background K+ Channels 381
B. K2P Channels Exhibit Diverse Functional Properties 382
VI. Summary 393
References 393
Chapter 13: Finding Sensory Neuron Mechanotransduction Components 399
I. Overview 399
II. Introduction 400
III. Mechanical Nociceptors and Other Relevant Mechanoreceptors 400
IV. Physiology of Transduction 403
V. Molecular Identity of the Transducer 405
A. Caenorhabditis elegans 405
B. Drosophila melanogaster 409
VI. Identification of Molecules Required for Vertebrate Sensory Mechanotransduction 410
VII. Candidate Gene Approaches 411
VIII. Are There Vertebrate mec Genes Involved in Sensory Mechanotransduction? 411
IX. Are TRP Channels Candidates for the Sensory Neuron Mechanotransducer? 415
X. Expression Cloning 418
XI. Imaging Mechanotransduction with Fluorescent Dyes 420
XII. Using DNA Microarrays to Find Transduction Components 420
XIII. Biochemical Approaches 424
XIV. Conclusions 426
References 426
Chapter 14: Functional Diversity of Voltage-Dependent Ca2+ Channels in Nociception: Recent Progress in Genetic Studies 435
I. Overview 435
II. Introduction 436
III. VDCC Family 437
A. L-Type Ca2+ Channels in Nociception 441
B. N-Type Ca2+ Channels 442
C. P/Q-Type Ca2+ Channels in Nociception 445
D. R-Type Ca2+ Channels in Antinociception 446
E. T-Type Ca2+ Channels 446
F. Auxiliary Subunits of Voltage-Dependent Ca2+ Channels 451
IV. Conclusions 452
References 453
Chapter 15: Expression Patterns and Histological Aspects of TRP Channels in Sensory Neurons 459
I. Overview 459
II. TRPV1 (VR1) 460
A. TRPV1 and TrkA 462
B. TRPV1 and SP 463
C. TRPV1 and CGRP 463
D. TRPV1 and P2X Receptors 464
E. TRPV1 and CB1 Receptor 465
F. TRPV1 and PKC 465
G. TRPV1 and PKA 465
H. TRPV1 and Somatostatin Receptor (SSTRs) 466
III. TRPV2 (VRL1) 466
IV. TRPV3 (Also Known as VRL3) 467
V. TRPV4 (Also Known as VRL-2/OTRPC4/VR-OAC/TRP12) 467
VI. TRPM8 (Also Known as CMR1) 468
VII. TRPA1 (Renamed from ANKTM1) 468
VIII. Conclusions 469
References 470
Subject Index 477
Erscheint lt. Verlag | 21.9.2011 |
---|---|
Mitarbeit |
Herausgeber (Serie): Dale J. Benos, Sidney A. Simon |
Sprache | englisch |
Themenwelt | Sachbuch/Ratgeber |
Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie | |
Naturwissenschaften ► Biologie ► Biochemie | |
Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie | |
Naturwissenschaften ► Biologie ► Zellbiologie | |
Naturwissenschaften ► Biologie ► Zoologie | |
Naturwissenschaften ► Physik / Astronomie ► Angewandte Physik | |
Technik | |
ISBN-10 | 0-08-046362-2 / 0080463622 |
ISBN-13 | 978-0-08-046362-9 / 9780080463629 |
Haben Sie eine Frage zum Produkt? |
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