Chasing Men on Fire: The Story of the Search for a Pain Gene

Chasing Men on Fire: The Story of the Search for a Pain Gene


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Product Details

ISBN-13: 9780262037402
Publisher: MIT Press
Publication date: 03/09/2018
Series: The MIT Press
Pages: 320
Product dimensions: 7.00(w) x 9.10(h) x 1.10(d)
Age Range: 18 Years

About the Author

Stephen G. Waxman is Bridget Flaherty Professor of Neurology, Neuroscience, and Pharmacology at Yale University, where he is also Director of the Center for Neuroscience and Regeneration Research. He is the author of Form and Function in the Brain and Spinal Cord (MIT Press) and other books.

Table of Contents

Foreword James E. Rothman ix

Preface xi

Acknowledgments xiii

Part I Dissecting God's Megaphone 1

1 Dissecting God's Megaphone: The Search for a Pain Gene 3

2 Sherrington's Enchanted Loom and Huxley's Science Fiction 9

Part II Chasing Men on Fire: The Search 23

3 Alabama to Beijing … and Back 25

Cummins et al.: Electrophysiological Properties of Mutant Nav1.7 Sodium Channels in a Painful Inherited Neuropathy 35

Dib-Hajj et al.: Gain-of-Function Mutation in Nav1.7 in Familial Erythromelalgia Induces Bursting of Sensory Neurons 45

4 Avalanche 57

Dib-Hajj et al.: The Nav1.7 Sodium Channel: From Molecule to Man 61

5 Two Sides of One Coin 85

Rush et al.: A Single Sodium Channel Mutation Produces Hyper- or Hypoexcitability in Different Types of Neurons 89

6 Eavesdropping 103

Vasylyev et al.: Dynamic-Clamp Analysis of Wild-Type Human Nav1.7 and Erythromelalgia Mutant Channel L858H 109

Part III Beyond the Search: Expanding Horizons 133

7 Twisted Nerve: A Ganglion Gone Awry 135

Black et al.: Multiple Sodium Channel Isoforms and Mitogen-Activated Protein Kinases Are Present in Painful Human Neuromas 139

8 Crossing Borders 155

9 From Zebras to Horses 163

Faber et al.: Gain of Function Nav1.7 Mutations in Idiopathic Small Fiber Neuropathy 175

Persson et al.: Neuropathy-Associated Nav1.7 Variant I228M Impairs Integrity of Dorsal Root Ganglion Neuron Axons 195

Part IV Muting God's Megaphone: From the Squid Toward the Clinic 213

11 Seven Years from Theory toward Therapy … via "Pain in a Dish" 215

Cao et al.: Pharmacological Reversal of a Pain Phenotype in iPSC-Derived Sensory Neurons and Patients with Inherited Erythromelalgia 225

12 From Trial-and-Error to First-Time-Around: Toward Genomically Guided Therapy 247

Yang et al.: Structural Modelling and Mutant Cycle Analysis Predict Pharmacoresponsiveness of a Nav1.7 Mutant Channel 251

13 Precision 271

Geha et al.: Pharmacotherapy for Pain in a Family with Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling 275

14 "The Important Thing Is Not to Stop" 289

Glossary 293

Index 297

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