Pain Genetics

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.

Auteur

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.

Résumé
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.

Contenu

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

GenotypePhenotype 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-...