In this Book

summary

Two soldiers, both with wounds injuring the same nerve, show very different responses: one is disabled by neuropathic pain, unable to touch the injured limb because even the lightest contact triggers excruciating discomfort; the other notices numbness but no pain at all. Could the difference lie in their genes? In this book, described in the foreword by Nobel Laureate James Rothman as "so well written that it reads like a detective novel," Stephen Waxman recounts the search for a gene that controls pain -- a search spanning more than thirty years and three continents.  The story moves from genes to pain-signaling neurons that scream when they should be silent to people with a rare genetic disorder who feel they are on fire. Waxman explains that if pain-signaling neurons are injured by trauma or disease, they can become hyperactive and send pain signals to the brain even without external stimulus. Studying the hyperactive mutant pain gene in man on fire syndrome has pointed the way to molecules that produce pain more broadly within the general population, in the rest of us. Waxman's account of the many steps that led to discovery of the pain gene tells the story behind the science, of how science happens.

Table of Contents

  1. Cover
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  1. Title Page, Copyright, Dedication
  2. pp. i-vi
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  1. CONTENTS
  2. pp. vii-viii
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  1. FOREWORD
  2. James E. Rothman
  3. pp. ix-x
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  1. PREFACE
  2. pp. xi-xii
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  1. ACKNOWLEDGMENTS
  2. pp. xiii-xiv
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  1. I DISSECTING GOD’S MEGAPHONE
  1. 1 DISSECTING GOD’S MEGAPHONE: THE SEARCH FOR A PAIN GENE
  2. pp. 3-8
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  1. 2 SHERRINGTON’S ENCHANTED LOOM AND HUXLEY’S SCIENCE FICTION
  2. pp. 9-22
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  1. II CHASING MEN ON FIRE: THE SEARCH
  1. 3 ALABAMA TO BEIJING … AND BACK
  2. pp. 25-34
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  1. ELECTROPHYSIOLOGICAL PROPERTIES OF MUTANT NaV1.7 SODIUM CHANNELS IN A PAINFUL INHERITED NEUROPATHY
  2. Theodore R. Cummins, Sulayman D. Dib-Hajj, and Stephen G. Waxman
  3. pp. 35-44
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  1. GAIN-OF-FUNCTION MUTATION IN NaV1.7 IN FAMILIAL ERYTHROMELALGIA INDUCES BURSTING OF SENSORY NEURONS
  2. S. D. Dib-Hajj, A. M. Rush, T. R. Cummins, F. M. Hisama, S. Novella, L. Tyrrell, L. Marshall, and S. G. Waxman
  3. pp. 45-56
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  1. 4 AVALANCHE
  2. pp. 57-60
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  1. THE NaV1.7 SODIUM CHANNEL: FROM MOLECULE TO MAN
  2. Sulayman D. Dib-Hajj, Yang Yang, Joel A. Black, and Stephen G. Waxman
  3. pp. 61-84
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  1. 5 TWO SIDES OF ONE COIN
  2. pp. 85-88
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  1. A SINGLE SODIUM CHANNEL MUTATION PRODUCES HYPEROR HYPOEXCITABILITY IN DIFFERENT TYPES OF NEURONS
  2. Anthony M. Rush, Sulayman D. Dib-Hajj, Shujun Liu, Theodore R. Cummins, Joel A. Black, and Stephen G. Waxman
  3. pp. 89-102
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  1. 6 EAVESDROPPING
  2. pp. 103-108
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  1. DYNAMIC-CLAMP ANALYSIS OF WILD-TYPE HUMAN NaV1.7 AND ERYTHROMELALGIA MUTANT CHANNEL L858H
  2. Dmytro V. Vasylyev, Chongyang Han, Peng Zhao, Sulayman Dib-Hajj, and Stephen G. Waxman
  3. pp. 109-132
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  1. III BEYOND THE SEARCH: EXPANDING HORIZONS
  1. 7 TWISTED NERVE: A GANGLION GONE AWRY
  2. pp. 135-138
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  1. MULTIPLE SODIUM CHANNEL ISOFORMS AND MITOGEN-ACTIVATED PROTEIN KINASES ARE PRESENT IN PAINFUL HUMAN NEUROMAS
  2. pp. 139-154
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  1. 8 CROSSING BORDERS
  2. pp. 155-162
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  1. 9 FROM ZEBRAS TO HORSES
  2. pp. 163-174
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  1. GAIN OF FUNCTION NaV1.7 MUTATIONS IN IDIOPATHIC SMALL FIBER NEUROPATHY
  2. Catharina G. Faber, Janneke G. J. Hoeijmakers, Hye-Sook Ahn, Xiaoyang Cheng, Chongyang Han, Jin-Sung Choi, Mark Estacion, Giuseppe Lauria, Els K. Vanhoutte, Monique M. Gerrits, Sulayman Dib-Hajj, Joost P. H. Drenth, Stephen G. Waxman, and Ingemar S. J. Merkies
  3. pp. 175-194
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  1. NEUROPATHY-ASSOCIATED NaV1.7 VARIANT I228M IMPAIRS INTEGRITY OF DORSAL ROOT GANGLION NEURON AXONS
  2. Anna-Karin Persson, Shujun Liu, Catharina G. Faber, Ingemar S. J. Merkies, Joel A. Black, and Stephen G. Waxman
  3. pp. 195-204
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  1. 10 RIPPLES
  2. pp. 205-212
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  1. IV MUTING GOD’S MEGAPHONE: FROM THE SQUID TOWARD THE CLINIC
  1. 11 SEVEN YEARS FROM THEORY TOWARD THERAPY … VIA “PAIN IN A DISH”
  2. pp. 215-224
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  1. PHARMACOLOGICAL REVERSAL OF A PAIN PHENOTYPE IN iPSC-DERIVED SENSORY NEURONS AND PATIENTS WITH INHERITED ERYTHROMELALGIA
  2. Lishuang Cao, Aoibhinn McDonnell, Anja Nitzsche, Aristos Alexandrou, Pierre-Philippe Saintot, Alexandre J.C. Loucif, Adam R. Brown, Gareth Young, Malgorzata Mis, Andrew Randall, Stephen G. Waxman, Philip Stanley, Simon Kirby, Sanela Tarabar, Alex Gutteridge, Richard Butt, Ruth M. McKernan, Paul Whiting, Zahid Ali, James Bilsland, and Edward B. Stevens
  3. pp. 225-246
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  1. 12 FROM TRIAL-AND-ERROR TO FIRST-TIME-AROUND: TOWARD GENOMICALLY GUIDED THERAPY
  2. pp. 247-250
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  1. STRUCTURAL MODELLING AND MUTANT CYCLE ANALYSIS PREDICT PHARMACORESPONSIVENESS OF A NaV1.7 MUTANT CHANNEL
  2. Yang Yang, Sulayman D. Dib-Hajj, Jian Zhang, Yang Zhang, Lynda Tyrrell, Mark Estacion, and Stephen G. Waxman
  3. pp. 251-270
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  1. 13 PRECISION
  2. pp. 271-274
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  1. PHARMACOTHERAPY FOR PAIN IN A FAMILY WITH INHERITED ERYTHROMELALGIA GUIDED BY GENOMIC ANALYSIS AND FUNCTIONAL PROFILING
  2. pp. 275-288
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  1. 14 “THE IMPORTANT THING IS NOT TO STOP”
  2. pp. 289-292
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  1. GLOSSARY
  2. pp. 293-296
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  1. INDEX
  2. pp. 297-304
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Additional Information

ISBN
9780262344722
Related ISBN
9780262037402
MARC Record
OCLC
1028188541
Pages
320
Launched on MUSE
2018-03-13
Language
English
Open Access
No
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