Pain Genetics (eBook, PDF)
Basic to Translational Science
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Pain Genetics (eBook, PDF)
Basic to Translational Science
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Pain Genetics: Basic to Translational Science is a timely synthesis of the key areas of research informing our understanding of the genetic basis of pain. The book opens with foundational information on basic genetic mechanisms underlying pain perception and progresses recently discovered complex concepts facing the field. The coverage is wide-ranging and will serves as an excellent entry point into understating the genetics of pain as well as providing a single resource for established researchers looking for a better understanding of the diverse strands of research going on in the area. With…mehr
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Pain Genetics: Basic to Translational Science is a timely synthesis of the key areas of research informing our understanding of the genetic basis of pain. The book opens with foundational information on basic genetic mechanisms underlying pain perception and progresses recently discovered complex concepts facing the field. The coverage is wide-ranging and will serves as an excellent entry point into understating the genetics of pain as well as providing a single resource for established researchers looking for a better understanding of the diverse strands of research going on in the area. With contributors painstakingly selected to provide a broad range of perspectives and research, Pain Genetics will be a valuable resource for geneticists, neuroscientists, and biomedical professionals alike.
Produktdetails
- Produktdetails
- Verlag: John Wiley & Sons
- Seitenzahl: 204
- Erscheinungstermin: 4. November 2013
- Englisch
- ISBN-13: 9781118398883
- Artikelnr.: 39951126
- Verlag: John Wiley & Sons
- Seitenzahl: 204
- Erscheinungstermin: 4. November 2013
- Englisch
- ISBN-13: 9781118398883
- Artikelnr.: 39951126
Inna Belfer, MD, PhD, is an Associate Professor of Anesthesiology and Human Genetics and Director of the Molecular Epidemiology of Pain Program at the Department of Anesthesiology, School of Medicine, University of Pittsburgh. Luda Diatchenko, MD, PhD, is a Canada Excellence Research Chair in Human Pain Genetics, Professor, Faculty of Medicine, Department of Anesthesia, and Faculty of Dentistry at McGill University, Alan Edwards Centre for Research on Pain.
Editors' Biographies xi Contributors xiii 1 How Do Pain Genes Affect Pain
Experience? 1 Marshall Devor Introduction 2 Heritability of Pain:
Historical Roots 2 Why is Pain Genetics Interesting and Potentially Useful?
4 What Are Pain Genes? 8 How Do Pain Genes Affect Pain Experience? 9
Disease Susceptibility Genes Versus Pain Susceptibility Genes 12
Perspective 13 Acknowledgments 13 2 Conservation of Pain Genes Across
Evolution 15 Thang Manh Khuong and G. Greg Neely Introduction 15 Anatomical
Organization of Nociception Apparatus in Mammals and Drosophila 16 Acute
Heat Pain in Mammals 16 Acute Heat Nociception in Drosophila 18 Mechanical
Pain in Mammals 19 Mechanical Nociception in Drosophila 19 Chemical
Nociception in Mammals 21 Chemical Nociception in Drosophila 21
Inflammatory Pain in Mammals 22 Persistent Pain in Drosophila 22
Neuropathic Pain in Mammals 25 Structural Reorganizations of Nerve Fibers
in Neuropathic Pain 25 Mammalian Neuropathic Pain Genes That Are Conserved
in Drosophila 25 Long-Term Potentiation and Long-Term Depression in
Neuropathic Pain in Mammals 28 Neuropathic Pain in Drosophila 30
Conclusions 30 3 Defining Human Pain Phenotypes for Genetic Association
Studies 37 Christopher Sivert Nielsen Introduction 37 What is a Pain
Phenotype? 38 Pain Scaling 39 Heritability 40 Genotype-Phenotype Matching
41 Reliability and Temporal Stability 41 Clinical Phenotypes 43 Designing
Clinical Pain Genetic Studies 43 The Heritability of Specific Clinical Pain
Conditions 45 Experimental Phenotypes 45 The Heritability of Experimental
Phenotypes 46 Extended Phenotypes 47 Practical Concerns 47 Conclusions 48
Conflict of Interest Statement 48 4 Genetic Contributions to Pain and
Analgesia: Interactions with Sex and Stress 51 Roger B. Fillingim and
Jeffrey S. Mogil Introduction 51 Brief Overview of Sex and Gender
Differences in Pain and Analgesia 52 Brief Overview of Stress and
Pain/Analgesia 52 Sex X Gene Interactions in Pain and Analgesia 53 Summary
57 5 Abnormal Pain Conditions in Humans Related to Genetic Mutations 61
Christopher Geoffrey Woods Introduction to SCN9A, NTRK1, and NGF and the
Roles They Play in Pain 61 Introduction to SCN9A and Its Omnipotent Role in
Pain Sensing 62 Introduction to NTRK1 and Its Role in Development and
Function in the Pain and Sympathetic Nervous Systems 69 Introduction to
NGF, the First Nerve Growth Factor to Be Found and Studied 72 6 Alternative
Pre-mRNA Splicing of Mu Opioid Receptor Gene: Molecular Mechanisms
Underlying the Complex Actions of Mu Opioids 79 Ying-Xian Pan Introduction
79 Evolution of OPRM1 Gene 80 OPRM1 Gene: Chromosomal Location and Gene
Structure 82 Alternative Promoters 82 Alternative Pre-mRNA Splicing of the
OPRM1 Gene 83 Expression and Function of the OPRM1 Splice Variants 90
Conclusion 94 7 Discovering Multilocus Associations with Complex Pain
Phenotypes 99 Chia-Ling Kuo, Luda Diatchenko, and Dmitri Zaykin
Introduction 99 Approaches Based on Testing Individual Genetic Variants
Within a Region 100 Approaches That Combine Association Signals Across
Genetic Variants 101 Methods for Testing Joint Effects of Multiple Genetic
Variants 102 Multilocus Analysis of Mu Opioid Receptor Haplotypes 103
Two-Stage Multilocus Association Analysis: Collapsing SNPs with Adjustment
for Effect Directions 104 Two-Stage Approach: Simulations 107 Two-Stage
Approach: Results 108 Discussion 111 Acknowledgments 113 8 Overlapping
Phenotypes: Genetic Contribution to Nausea and Pain 115 Charles C. Horn
Introduction 115 What is the Functional Role of Nausea and Vomiting? 117
Pain Syndromes with Significant Nausea 118 The Neuropharmacology of Nausea
and Emesis 119 Emetic and Antiemetic Action of Opioids 121 Preclinical
Studies of Nausea and Vomiting 122 Heritability of Nausea and Vomiting
Phenotypes 123 Human Genetic Sequence Variants Associated with Nausea and
Vomiting 124 Summary and Future Directions 125 9 A Counterpart to Pain:
Itch 131 Adam P. Kardon and Sarah E. Ross Introduction 131 Why Do We
Scratch? 132 The Basics of Itch 132 So How is Itch Coded? 133 Measuring
Itch in Mice 134 Genetic Models of Itch 135 A Key Role for the Skin in Itch
141 A Shift in the Balance of Pain and Itch 141 Genetic Variation and Itch
in Humans - Challenges for the Future 143 Acknowledgments 143 10
Translating Genetic Knowledge into Clinical Practice for Musculoskeletal
Pain Conditions 147 Luda Diatchenko, Shad B. Smith, and William Maixner
Introduction 147 Results of Human Association Studies 148 Gene Sequencing
150 Development of New Therapeutics 150 Understanding of Interactions 155
In Summary 156 11 The Human Chronic Pain Phenome: Mapping Nongenetic
Modifiers of the Heritable Risk 161 Ze'ev Seltzer, Scott R. Diehl, Hance
Clarke, and Joel Katz The Current Crisis in Pain Medicine 162 The
Importance of Estimating Risk of Chronic Neuropathic Pain (CNP) 162
Modification of the Heritable Risk for CNP 163 The Natural History of CNP
165 Modification of Heritable Risk for CNP In Utero 166 Modifications of
the Heritable Risk for CNP Across Generations 167 Postnatal Modifications
of the Heritable Risk for CNP 168 Modifications of the Heritable Risk for
CNP by Childhood Adverse Experiences 168 Modifications of the Heritable
Risk for CNP by Prior Chronic Pain Epochs 169 Modification of the Heritable
Risk for CNP by Certain Personality Traits 172 Modification of the
Heritable Risk for CNP by Social Factors 172 Modification of the Heritable
Risk for CNP by Diet, Medications, Smoking, and Alcohol Intake Consumed
Preoperatively 174 Modification of the Heritable Risk for CNP by Climate
175 Modification of the Heritable Risk for CNP by Lifestyle 175
Modifications of the Heritable Risk for Chronic Pain by Other Diseases 176
Modifications of the Heritable Risk for CNP by Nongenetic Factors Occurring
Just Prior and During the Inciting Event 176 Summary 177 Appendix: List of
Abbreviations 183 Index 185 Color insert found between pages 114 and 115
Experience? 1 Marshall Devor Introduction 2 Heritability of Pain:
Historical Roots 2 Why is Pain Genetics Interesting and Potentially Useful?
4 What Are Pain Genes? 8 How Do Pain Genes Affect Pain Experience? 9
Disease Susceptibility Genes Versus Pain Susceptibility Genes 12
Perspective 13 Acknowledgments 13 2 Conservation of Pain Genes Across
Evolution 15 Thang Manh Khuong and G. Greg Neely Introduction 15 Anatomical
Organization of Nociception Apparatus in Mammals and Drosophila 16 Acute
Heat Pain in Mammals 16 Acute Heat Nociception in Drosophila 18 Mechanical
Pain in Mammals 19 Mechanical Nociception in Drosophila 19 Chemical
Nociception in Mammals 21 Chemical Nociception in Drosophila 21
Inflammatory Pain in Mammals 22 Persistent Pain in Drosophila 22
Neuropathic Pain in Mammals 25 Structural Reorganizations of Nerve Fibers
in Neuropathic Pain 25 Mammalian Neuropathic Pain Genes That Are Conserved
in Drosophila 25 Long-Term Potentiation and Long-Term Depression in
Neuropathic Pain in Mammals 28 Neuropathic Pain in Drosophila 30
Conclusions 30 3 Defining Human Pain Phenotypes for Genetic Association
Studies 37 Christopher Sivert Nielsen Introduction 37 What is a Pain
Phenotype? 38 Pain Scaling 39 Heritability 40 Genotype-Phenotype Matching
41 Reliability and Temporal Stability 41 Clinical Phenotypes 43 Designing
Clinical Pain Genetic Studies 43 The Heritability of Specific Clinical Pain
Conditions 45 Experimental Phenotypes 45 The Heritability of Experimental
Phenotypes 46 Extended Phenotypes 47 Practical Concerns 47 Conclusions 48
Conflict of Interest Statement 48 4 Genetic Contributions to Pain and
Analgesia: Interactions with Sex and Stress 51 Roger B. Fillingim and
Jeffrey S. Mogil Introduction 51 Brief Overview of Sex and Gender
Differences in Pain and Analgesia 52 Brief Overview of Stress and
Pain/Analgesia 52 Sex X Gene Interactions in Pain and Analgesia 53 Summary
57 5 Abnormal Pain Conditions in Humans Related to Genetic Mutations 61
Christopher Geoffrey Woods Introduction to SCN9A, NTRK1, and NGF and the
Roles They Play in Pain 61 Introduction to SCN9A and Its Omnipotent Role in
Pain Sensing 62 Introduction to NTRK1 and Its Role in Development and
Function in the Pain and Sympathetic Nervous Systems 69 Introduction to
NGF, the First Nerve Growth Factor to Be Found and Studied 72 6 Alternative
Pre-mRNA Splicing of Mu Opioid Receptor Gene: Molecular Mechanisms
Underlying the Complex Actions of Mu Opioids 79 Ying-Xian Pan Introduction
79 Evolution of OPRM1 Gene 80 OPRM1 Gene: Chromosomal Location and Gene
Structure 82 Alternative Promoters 82 Alternative Pre-mRNA Splicing of the
OPRM1 Gene 83 Expression and Function of the OPRM1 Splice Variants 90
Conclusion 94 7 Discovering Multilocus Associations with Complex Pain
Phenotypes 99 Chia-Ling Kuo, Luda Diatchenko, and Dmitri Zaykin
Introduction 99 Approaches Based on Testing Individual Genetic Variants
Within a Region 100 Approaches That Combine Association Signals Across
Genetic Variants 101 Methods for Testing Joint Effects of Multiple Genetic
Variants 102 Multilocus Analysis of Mu Opioid Receptor Haplotypes 103
Two-Stage Multilocus Association Analysis: Collapsing SNPs with Adjustment
for Effect Directions 104 Two-Stage Approach: Simulations 107 Two-Stage
Approach: Results 108 Discussion 111 Acknowledgments 113 8 Overlapping
Phenotypes: Genetic Contribution to Nausea and Pain 115 Charles C. Horn
Introduction 115 What is the Functional Role of Nausea and Vomiting? 117
Pain Syndromes with Significant Nausea 118 The Neuropharmacology of Nausea
and Emesis 119 Emetic and Antiemetic Action of Opioids 121 Preclinical
Studies of Nausea and Vomiting 122 Heritability of Nausea and Vomiting
Phenotypes 123 Human Genetic Sequence Variants Associated with Nausea and
Vomiting 124 Summary and Future Directions 125 9 A Counterpart to Pain:
Itch 131 Adam P. Kardon and Sarah E. Ross Introduction 131 Why Do We
Scratch? 132 The Basics of Itch 132 So How is Itch Coded? 133 Measuring
Itch in Mice 134 Genetic Models of Itch 135 A Key Role for the Skin in Itch
141 A Shift in the Balance of Pain and Itch 141 Genetic Variation and Itch
in Humans - Challenges for the Future 143 Acknowledgments 143 10
Translating Genetic Knowledge into Clinical Practice for Musculoskeletal
Pain Conditions 147 Luda Diatchenko, Shad B. Smith, and William Maixner
Introduction 147 Results of Human Association Studies 148 Gene Sequencing
150 Development of New Therapeutics 150 Understanding of Interactions 155
In Summary 156 11 The Human Chronic Pain Phenome: Mapping Nongenetic
Modifiers of the Heritable Risk 161 Ze'ev Seltzer, Scott R. Diehl, Hance
Clarke, and Joel Katz The Current Crisis in Pain Medicine 162 The
Importance of Estimating Risk of Chronic Neuropathic Pain (CNP) 162
Modification of the Heritable Risk for CNP 163 The Natural History of CNP
165 Modification of Heritable Risk for CNP In Utero 166 Modifications of
the Heritable Risk for CNP Across Generations 167 Postnatal Modifications
of the Heritable Risk for CNP 168 Modifications of the Heritable Risk for
CNP by Childhood Adverse Experiences 168 Modifications of the Heritable
Risk for CNP by Prior Chronic Pain Epochs 169 Modification of the Heritable
Risk for CNP by Certain Personality Traits 172 Modification of the
Heritable Risk for CNP by Social Factors 172 Modification of the Heritable
Risk for CNP by Diet, Medications, Smoking, and Alcohol Intake Consumed
Preoperatively 174 Modification of the Heritable Risk for CNP by Climate
175 Modification of the Heritable Risk for CNP by Lifestyle 175
Modifications of the Heritable Risk for Chronic Pain by Other Diseases 176
Modifications of the Heritable Risk for CNP by Nongenetic Factors Occurring
Just Prior and During the Inciting Event 176 Summary 177 Appendix: List of
Abbreviations 183 Index 185 Color insert found between pages 114 and 115
Editors' Biographies xi Contributors xiii 1 How Do Pain Genes Affect Pain
Experience? 1 Marshall Devor Introduction 2 Heritability of Pain:
Historical Roots 2 Why is Pain Genetics Interesting and Potentially Useful?
4 What Are Pain Genes? 8 How Do Pain Genes Affect Pain Experience? 9
Disease Susceptibility Genes Versus Pain Susceptibility Genes 12
Perspective 13 Acknowledgments 13 2 Conservation of Pain Genes Across
Evolution 15 Thang Manh Khuong and G. Greg Neely Introduction 15 Anatomical
Organization of Nociception Apparatus in Mammals and Drosophila 16 Acute
Heat Pain in Mammals 16 Acute Heat Nociception in Drosophila 18 Mechanical
Pain in Mammals 19 Mechanical Nociception in Drosophila 19 Chemical
Nociception in Mammals 21 Chemical Nociception in Drosophila 21
Inflammatory Pain in Mammals 22 Persistent Pain in Drosophila 22
Neuropathic Pain in Mammals 25 Structural Reorganizations of Nerve Fibers
in Neuropathic Pain 25 Mammalian Neuropathic Pain Genes That Are Conserved
in Drosophila 25 Long-Term Potentiation and Long-Term Depression in
Neuropathic Pain in Mammals 28 Neuropathic Pain in Drosophila 30
Conclusions 30 3 Defining Human Pain Phenotypes for Genetic Association
Studies 37 Christopher Sivert Nielsen Introduction 37 What is a Pain
Phenotype? 38 Pain Scaling 39 Heritability 40 Genotype-Phenotype Matching
41 Reliability and Temporal Stability 41 Clinical Phenotypes 43 Designing
Clinical Pain Genetic Studies 43 The Heritability of Specific Clinical Pain
Conditions 45 Experimental Phenotypes 45 The Heritability of Experimental
Phenotypes 46 Extended Phenotypes 47 Practical Concerns 47 Conclusions 48
Conflict of Interest Statement 48 4 Genetic Contributions to Pain and
Analgesia: Interactions with Sex and Stress 51 Roger B. Fillingim and
Jeffrey S. Mogil Introduction 51 Brief Overview of Sex and Gender
Differences in Pain and Analgesia 52 Brief Overview of Stress and
Pain/Analgesia 52 Sex X Gene Interactions in Pain and Analgesia 53 Summary
57 5 Abnormal Pain Conditions in Humans Related to Genetic Mutations 61
Christopher Geoffrey Woods Introduction to SCN9A, NTRK1, and NGF and the
Roles They Play in Pain 61 Introduction to SCN9A and Its Omnipotent Role in
Pain Sensing 62 Introduction to NTRK1 and Its Role in Development and
Function in the Pain and Sympathetic Nervous Systems 69 Introduction to
NGF, the First Nerve Growth Factor to Be Found and Studied 72 6 Alternative
Pre-mRNA Splicing of Mu Opioid Receptor Gene: Molecular Mechanisms
Underlying the Complex Actions of Mu Opioids 79 Ying-Xian Pan Introduction
79 Evolution of OPRM1 Gene 80 OPRM1 Gene: Chromosomal Location and Gene
Structure 82 Alternative Promoters 82 Alternative Pre-mRNA Splicing of the
OPRM1 Gene 83 Expression and Function of the OPRM1 Splice Variants 90
Conclusion 94 7 Discovering Multilocus Associations with Complex Pain
Phenotypes 99 Chia-Ling Kuo, Luda Diatchenko, and Dmitri Zaykin
Introduction 99 Approaches Based on Testing Individual Genetic Variants
Within a Region 100 Approaches That Combine Association Signals Across
Genetic Variants 101 Methods for Testing Joint Effects of Multiple Genetic
Variants 102 Multilocus Analysis of Mu Opioid Receptor Haplotypes 103
Two-Stage Multilocus Association Analysis: Collapsing SNPs with Adjustment
for Effect Directions 104 Two-Stage Approach: Simulations 107 Two-Stage
Approach: Results 108 Discussion 111 Acknowledgments 113 8 Overlapping
Phenotypes: Genetic Contribution to Nausea and Pain 115 Charles C. Horn
Introduction 115 What is the Functional Role of Nausea and Vomiting? 117
Pain Syndromes with Significant Nausea 118 The Neuropharmacology of Nausea
and Emesis 119 Emetic and Antiemetic Action of Opioids 121 Preclinical
Studies of Nausea and Vomiting 122 Heritability of Nausea and Vomiting
Phenotypes 123 Human Genetic Sequence Variants Associated with Nausea and
Vomiting 124 Summary and Future Directions 125 9 A Counterpart to Pain:
Itch 131 Adam P. Kardon and Sarah E. Ross Introduction 131 Why Do We
Scratch? 132 The Basics of Itch 132 So How is Itch Coded? 133 Measuring
Itch in Mice 134 Genetic Models of Itch 135 A Key Role for the Skin in Itch
141 A Shift in the Balance of Pain and Itch 141 Genetic Variation and Itch
in Humans - Challenges for the Future 143 Acknowledgments 143 10
Translating Genetic Knowledge into Clinical Practice for Musculoskeletal
Pain Conditions 147 Luda Diatchenko, Shad B. Smith, and William Maixner
Introduction 147 Results of Human Association Studies 148 Gene Sequencing
150 Development of New Therapeutics 150 Understanding of Interactions 155
In Summary 156 11 The Human Chronic Pain Phenome: Mapping Nongenetic
Modifiers of the Heritable Risk 161 Ze'ev Seltzer, Scott R. Diehl, Hance
Clarke, and Joel Katz The Current Crisis in Pain Medicine 162 The
Importance of Estimating Risk of Chronic Neuropathic Pain (CNP) 162
Modification of the Heritable Risk for CNP 163 The Natural History of CNP
165 Modification of Heritable Risk for CNP In Utero 166 Modifications of
the Heritable Risk for CNP Across Generations 167 Postnatal Modifications
of the Heritable Risk for CNP 168 Modifications of the Heritable Risk for
CNP by Childhood Adverse Experiences 168 Modifications of the Heritable
Risk for CNP by Prior Chronic Pain Epochs 169 Modification of the Heritable
Risk for CNP by Certain Personality Traits 172 Modification of the
Heritable Risk for CNP by Social Factors 172 Modification of the Heritable
Risk for CNP by Diet, Medications, Smoking, and Alcohol Intake Consumed
Preoperatively 174 Modification of the Heritable Risk for CNP by Climate
175 Modification of the Heritable Risk for CNP by Lifestyle 175
Modifications of the Heritable Risk for Chronic Pain by Other Diseases 176
Modifications of the Heritable Risk for CNP by Nongenetic Factors Occurring
Just Prior and During the Inciting Event 176 Summary 177 Appendix: List of
Abbreviations 183 Index 185 Color insert found between pages 114 and 115
Experience? 1 Marshall Devor Introduction 2 Heritability of Pain:
Historical Roots 2 Why is Pain Genetics Interesting and Potentially Useful?
4 What Are Pain Genes? 8 How Do Pain Genes Affect Pain Experience? 9
Disease Susceptibility Genes Versus Pain Susceptibility Genes 12
Perspective 13 Acknowledgments 13 2 Conservation of Pain Genes Across
Evolution 15 Thang Manh Khuong and G. Greg Neely Introduction 15 Anatomical
Organization of Nociception Apparatus in Mammals and Drosophila 16 Acute
Heat Pain in Mammals 16 Acute Heat Nociception in Drosophila 18 Mechanical
Pain in Mammals 19 Mechanical Nociception in Drosophila 19 Chemical
Nociception in Mammals 21 Chemical Nociception in Drosophila 21
Inflammatory Pain in Mammals 22 Persistent Pain in Drosophila 22
Neuropathic Pain in Mammals 25 Structural Reorganizations of Nerve Fibers
in Neuropathic Pain 25 Mammalian Neuropathic Pain Genes That Are Conserved
in Drosophila 25 Long-Term Potentiation and Long-Term Depression in
Neuropathic Pain in Mammals 28 Neuropathic Pain in Drosophila 30
Conclusions 30 3 Defining Human Pain Phenotypes for Genetic Association
Studies 37 Christopher Sivert Nielsen Introduction 37 What is a Pain
Phenotype? 38 Pain Scaling 39 Heritability 40 Genotype-Phenotype Matching
41 Reliability and Temporal Stability 41 Clinical Phenotypes 43 Designing
Clinical Pain Genetic Studies 43 The Heritability of Specific Clinical Pain
Conditions 45 Experimental Phenotypes 45 The Heritability of Experimental
Phenotypes 46 Extended Phenotypes 47 Practical Concerns 47 Conclusions 48
Conflict of Interest Statement 48 4 Genetic Contributions to Pain and
Analgesia: Interactions with Sex and Stress 51 Roger B. Fillingim and
Jeffrey S. Mogil Introduction 51 Brief Overview of Sex and Gender
Differences in Pain and Analgesia 52 Brief Overview of Stress and
Pain/Analgesia 52 Sex X Gene Interactions in Pain and Analgesia 53 Summary
57 5 Abnormal Pain Conditions in Humans Related to Genetic Mutations 61
Christopher Geoffrey Woods Introduction to SCN9A, NTRK1, and NGF and the
Roles They Play in Pain 61 Introduction to SCN9A and Its Omnipotent Role in
Pain Sensing 62 Introduction to NTRK1 and Its Role in Development and
Function in the Pain and Sympathetic Nervous Systems 69 Introduction to
NGF, the First Nerve Growth Factor to Be Found and Studied 72 6 Alternative
Pre-mRNA Splicing of Mu Opioid Receptor Gene: Molecular Mechanisms
Underlying the Complex Actions of Mu Opioids 79 Ying-Xian Pan Introduction
79 Evolution of OPRM1 Gene 80 OPRM1 Gene: Chromosomal Location and Gene
Structure 82 Alternative Promoters 82 Alternative Pre-mRNA Splicing of the
OPRM1 Gene 83 Expression and Function of the OPRM1 Splice Variants 90
Conclusion 94 7 Discovering Multilocus Associations with Complex Pain
Phenotypes 99 Chia-Ling Kuo, Luda Diatchenko, and Dmitri Zaykin
Introduction 99 Approaches Based on Testing Individual Genetic Variants
Within a Region 100 Approaches That Combine Association Signals Across
Genetic Variants 101 Methods for Testing Joint Effects of Multiple Genetic
Variants 102 Multilocus Analysis of Mu Opioid Receptor Haplotypes 103
Two-Stage Multilocus Association Analysis: Collapsing SNPs with Adjustment
for Effect Directions 104 Two-Stage Approach: Simulations 107 Two-Stage
Approach: Results 108 Discussion 111 Acknowledgments 113 8 Overlapping
Phenotypes: Genetic Contribution to Nausea and Pain 115 Charles C. Horn
Introduction 115 What is the Functional Role of Nausea and Vomiting? 117
Pain Syndromes with Significant Nausea 118 The Neuropharmacology of Nausea
and Emesis 119 Emetic and Antiemetic Action of Opioids 121 Preclinical
Studies of Nausea and Vomiting 122 Heritability of Nausea and Vomiting
Phenotypes 123 Human Genetic Sequence Variants Associated with Nausea and
Vomiting 124 Summary and Future Directions 125 9 A Counterpart to Pain:
Itch 131 Adam P. Kardon and Sarah E. Ross Introduction 131 Why Do We
Scratch? 132 The Basics of Itch 132 So How is Itch Coded? 133 Measuring
Itch in Mice 134 Genetic Models of Itch 135 A Key Role for the Skin in Itch
141 A Shift in the Balance of Pain and Itch 141 Genetic Variation and Itch
in Humans - Challenges for the Future 143 Acknowledgments 143 10
Translating Genetic Knowledge into Clinical Practice for Musculoskeletal
Pain Conditions 147 Luda Diatchenko, Shad B. Smith, and William Maixner
Introduction 147 Results of Human Association Studies 148 Gene Sequencing
150 Development of New Therapeutics 150 Understanding of Interactions 155
In Summary 156 11 The Human Chronic Pain Phenome: Mapping Nongenetic
Modifiers of the Heritable Risk 161 Ze'ev Seltzer, Scott R. Diehl, Hance
Clarke, and Joel Katz The Current Crisis in Pain Medicine 162 The
Importance of Estimating Risk of Chronic Neuropathic Pain (CNP) 162
Modification of the Heritable Risk for CNP 163 The Natural History of CNP
165 Modification of Heritable Risk for CNP In Utero 166 Modifications of
the Heritable Risk for CNP Across Generations 167 Postnatal Modifications
of the Heritable Risk for CNP 168 Modifications of the Heritable Risk for
CNP by Childhood Adverse Experiences 168 Modifications of the Heritable
Risk for CNP by Prior Chronic Pain Epochs 169 Modification of the Heritable
Risk for CNP by Certain Personality Traits 172 Modification of the
Heritable Risk for CNP by Social Factors 172 Modification of the Heritable
Risk for CNP by Diet, Medications, Smoking, and Alcohol Intake Consumed
Preoperatively 174 Modification of the Heritable Risk for CNP by Climate
175 Modification of the Heritable Risk for CNP by Lifestyle 175
Modifications of the Heritable Risk for Chronic Pain by Other Diseases 176
Modifications of the Heritable Risk for CNP by Nongenetic Factors Occurring
Just Prior and During the Inciting Event 176 Summary 177 Appendix: List of
Abbreviations 183 Index 185 Color insert found between pages 114 and 115