Molecular Pain - Springer978-0-387-75269-3/1.pdf · book on molecular pain. A scenery view of the...

Min Zhuo Editor

Molecular Pain

ag»wai)isa ^ Snringer Higher Education Press _ ' ^ r - - ^S

Min Zhuo

Department of Physiology

University of Toronto

Medical Sciences Bldg, Rm 3342

1 King's College Circle

Toronto, Ontario, Canada M5S 1A8

E-mail: [email protected]

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^«e^^^^ ; iS=Molecu la rPa in / ( ^ ) 4 S ( ± l i . :lk^: ffi^itWHilStt, 2007.10

ISBN 978-7-04-018954^

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Copyright © 2007 by

Higher Education Press 4 Dewai Dajie, Beijing 100011, R R. China

Distributed by Springer Science+Business Media, LLC under ISBN 978-0-387-75268-6 worldwide except in

mainland China by the arrangement of Higher Education Press.

All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means,

electronic or mechanical, including photocopying, recording or by any information storage and retrieval system,

without permission in writing from the Publisher

While the advice and information in this book are believed to be true and accurate at the date of going to press,

neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or

omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material

contained herein.

ISBN 978-7-04-018954-4

Printed in R R. China

mailto:[email protected]

Major Contributors

Lan Bao, MD, PhD Principal Investigator, Professor

Laboratory of Molecular Cell Biology

Institute of Biochemistry and Cell Biology

Chinese Academy of Sciences

No. 320 Yue Yang Rd

Shanghai 200031, China

Phone:86-21-54921764

Fax: 86-21-54921762

E-mail: [email protected],cn

Haruhiko Bito, MD, PhD Associate Professor and Head

Department of Neurochemistry

The University of Tokyo, Graduate School of Medi-

cine

7-3-1 Kongo, Bunkyo-ku

Tokyo 113-0033, Japan

Phone:81-3-5841-3559

Fax:81-3-3814-8154

E-mail: [email protected],jp

Yves De Koninck, PhD Professor and Director

Department of Psychiatry

Centre de recherche Universite Laval Robert-Giffard

(CRULRG)

2601, Chemin de la Canardiere

Bureau F-5579 Beauport (Quebec) Gl J 2G3, Canada

Phone: 418-663-5747 ext 6885

Fax:418-663-5873 E-mail: [email protected]

Alaa El-Husseini, PhD Assistant Professor and Invesitgator

Brain Research Centre

University of British Columbia

Department of Psychiatry

Room 4N2-2255 Wesbrook Mall

Vancouver BC V6T 1Z3, Canada

Phone: 604-822-7526

Fax:604-822-7981


Paul W. Frankland, PhD Canada Research Chair in Cognitive Neurobiology

Hospital for Sick Children Research Institute

Department of Integrative Biology

555 University Ave.

Toronto ON M5G 1X8, Canada

Phone: 416-813-7654 extl823

Fax:416-813-6846


Gerald R Gebhart, PhD Professor and Director

Center for Pain Research

University of Pittsburgh

Pittsburgh PA 15213, USA

Phone:412-383-5911



ii Major Contributors

Fax: 412-383-5466


Peter A. Goldstein, MD Assistant Professor

Department of Anesthesiology

Weill Medical College

Cornell University

NewYorkNY 10021, USA

Phone: 212-746-5325

Fax: 212-746-4879


Jianguo G. Gu, PhD Associate Professor

Department of Oral & Maxillofacial Surgery & Di-

agnostic Sciences

College of Dentistry and McKnight Brain Institute

University of Florida

Box 100416

1600 SW Archer Road

Gainesville, Florida 32610, USA

Phone: 352-392-5989

Fax: 352-392-7609


Sheena Josselyn, PhD

Assistant Professor

Department of Brain & Behavior

Hospital for Sick Children Research Institute

McMaster Bldg Rm 4017B, 555 University Ave


Phone: 416-813-7654 ext.1824

Fax:416-813-6846


Bong-Kiun Kaang, PhD Professor

Neurobiology Laboratory

Department of Biological Sciences

& Institute of Molecular Biology & Genetics

College of Natural Sciences

Seoul National University

San 56-1 Silim-dong Kwanak-gu

Seoul 151-742, Korea

Phone: 82-2-880-7525

Fax: 82-2-884-9577


Jon H. Kaas, PhD Distinguished Professor, Department of Psychology

Associate Professor, Department of Cell Biology

Kennedy Center Investigator

Vanderbilt University

Department of Psychology

301 Wilson Hall

Nashville TN 37240, USA

Phone: 615-322-6029

Fax: 615-343-8449


Rohini Kuner, PhD Principal Investigator

Institute of Pharmacology

University of Heidelberg

Department of Molecular Pharmacology

366 IM Neuenheimer Feld

Heidelberg 69120, Germany

Phone: 49-6221-54-8289

Fax: 49-6221-54-8549


John R MacDonald, PhD

Ernest B. and Leonard B. Smith Professor and Chair

Physiology




Toronto ON M5S 1A8, Canada

Phone:416-978-0711

Fax: 416-978-4940


Annika Malmberg, PhD Principal Scientist, Head of Analgesia Discovery Re-

search and Head of in Vivo Analgesia









Major Contributors iii

Elan Pharmaceuticals

800 Gateway Boulevard

South San Francsico CA 94080, USA

Phone: 650-794-4253

Fax: 650-877-7486


Christophe MuUe, PhD

Professor and Director

Institut Francois Magendie

Universite Victor Segalen Bordeaux 2

1 rue C. Saint-Saens

Bordeaux 33077, France

Phone: 0557574086

Fax: 0557574082


Timothy J. Ness, MD, PhD Professor and Co-Director

University of Alabama Birmingham

Department of Anesthesiology

619 19th St SZRB 940

Birmingham AL 35233-6810, USA

Phone: 205-975-9643

Fax: 205-934-7437


Volker E. Neugebauer, MD, PhD Associate Professor

Department of Anatomy & Neurosciences

The University of Texas Medical Branch

Galveston TX 77555-1069, USA

Phone: 409-772-2124

Fax: 409-772-2789


Zhizhong Z. Pan, PhD Assistant Professor

The University of Texas-MD Anderson Cancer Center

Department of Anesthesiology and Pain Medicine

Division of Anesthesiology and Critical Care

1515 Holcombe Blvd.

Houston TX 77030, USA

Phone: 713-792-5559

Fax: 713-745-4754


Huixin Qi, PhD Research Assistant Professor

Department of Psychology

Vanderbilt University

Nashville TN 37203, USA

Phone: 615-322-7491

Fax: 615-343-8449


Alfredo Riberio-da-Silva, PhD Professor

McGill University

Department of Pharmacology & Therapeutics

Department of Anatomy & Cell Biology

3655 Prom. Sir William Osier

Montreal, Quebec, H3G 1Y6, Canada

Phone:514-398-3619

Fax: 514-398-6690


Michael W. Salter, MD, PhD Canada Research Chair in Neuroplasticity and Pain

(Tier I)

Senior Scientist, Programs in Brain and Behaviour

and Cell Biology

The Hospital for Sick Children

Professor of Physiology; Director, University of To-

ronto Centre for the Study of Pain


Elizabeth McMaster Bldg 555 University Ave, Rm

5018

Toronto ON M5G1X8, Canada

Phone:416-813-6272

Fax:416-813-7921


Kathleen A. Sluka, PT, PhD Associate Professor

Graduate Program in Physical Therapy & Rehabilita-









iv Major Contributors

tion Science

University of Iowa, Iowa, USA

1-242 Medical Education Building

Iowa City, Iowa 52242-1190, USA

Phone: 319-335-9791 or 9799

Fax:319-335-9707


search & Division of Neurology

The Hospital for Sick Children (HSC)

555 University Ave


Phone:416-813-8711

Fax:416-813-5086


Stefan Strack, PhD Assistant Professor

Department of Pharmacology

University of Iowa, College of Medicine

2-432 BSB

Iowa City lA 52242, USA

Phone:319-335-7965

Fax:319-338-8930


Andrew J. Todd, PhD Professor

Institute of Biomedical and Life Sciences

University of Glasgow

West Medical Building University Avenue

Glasgow G12 8QQYT, UK

Phone: 441413305868

Fax: 441413302868


Makoto Tominaga, MD, PhD Professor

Okazaki Institute of Integrative Bioscience

Section Cell Signaling

Higashiyama 5-1 Myodaiji

Okazaki 444-8787, Japan

Phone: 81-5-6459-5286

Fax: 81-5-6459-5285


Lu-Yang Wang, PhD Associate Professor

Department of Physiology, University of Toronto

Canada Research Chair in Brain & Behavior (Tier II)

Senior Scientist, Program in Brain and Behavior Re-

Ling-Gang Wu, PhD

Investigator

National Institute of Neurological Disorders and Stroke

36 Convent Drive, Bldg 36, Rm. 1C12

Bethesda, MD 20892, USA

Phone:301-451-3338

Fax: 301-480-1466


Tian-Le Xu, PhD Investigator and Chief

Laboratory of Synaptic Physiology

Institute of Neuroscience


No.320 Yue Yang Rd


Phone:86-21-54921751

Fax: 86-21-54921735


Megumu Yoshimura, MD, PhD Professor and Chair

Department of Integrative Physiology

Graduate School of Medical Sciences

Kyushu University

3-1-1 Maidashi, Higashi-ku

Fukuoka 812-8582, Japan

Phone: 81-9-2642-6085

Fax: 81-9-2642-6093


Xu Zhang, MD, PhD

Principal Investigator and Professor

Laboratory Sensory Sys

Institute Neuro Science










No.320YueYangRd


Phone: 86-21-54921761

Fax: 86-21-64713446


Zhi-Qi Zhao, PhD

Professor

Institute of Neurobiology

Fudan University

Shanghai 200433, China.

Phone: 86-21-55522878

Fax: 86-21-55522876


Major Contributors v

Min Zhuo, Ph D Canada Research Chair in Pain and Cognition, Tier I

EJLB-CIHR Michael Smith Chair in Neurosciences

and Mental Health

Professor



Medical Sciences Bldg, Rm 3342


Toronto, Ontario, M5S 1A8, Canada

Phone: 416-946-0532

Fax: 416-978-4940





Preface

T he initial idea for this book came from Dr.

Li Bingxiang at Higher Education Press

during an international symposium in

beautiftil southern China. Unlike traditional textbooks

on pain, she proposed I write a new book that in-

cluded recent progress in the neurobiology of pain.

This idea revived my long-term interest in editing a

book on molecular pain.

A scenery view of the southern China.

There are at least four major reasons why I felt

this book was necessary. First, there are only a few

textbooks on pain available, and some of them are

outdated.

Second, the existing pain textbooks mainly focus

on basic animal research and the clinical treatment

of pain. Due to space limitations and the breadth

of the topic, coverage of basic neuroscience is not

sufficient.

Third, molecular biologists are making rapid

progress toward finding molecular and gene involve-

ment in pain. This progress is visible in a number of

ways: the gene-chip used in pharmaceutical compa-

nies; the increase in molecular biologists interested in

pain; and the use of transgenic mice in pain research.

These scientists must be brought together with pain

scientists.

And finally, an integrative approach is becoming

standard in pain research. New investigators in the

field need to be trained in multiple aspects of neuro-

biology.

Support from my friends and fellow scientists

was essential to this book. The idea for this book was

met with a strong positive response from many scien-

tists, though not all of them could contribute chapters

due to personal time constraints. I am confident that

many of these excellent scientists will be able to con-

tribute new chapters to future editions.

Help from Michelle and Melissa was essential to

ii Preface

put this book together. Funding from the EJLB-CIHR

Michael Smith Chair and the Canada research Chair

made it possible for me to work on this book. Addi-

tional help from lab members was also appreciated.

My wife Kelly and my daughters Morgan and Dan-

ielle gave me enough energy and support to take on

this rather difficult task.

I look forward to hearing readers' suggestions

and comments on the book, though I know that not

every pain-related topic is fully covered. In most

cases, experts were contacted to write a chapter, but

couldn't due to various commitments. This book is

not intended to cover every topic related to pain; for

instance, I have skipped over discussion of sensory

receptors and the genetic background of pain. My

goal was to focus on several topics in which neuro-

science and pain interact to produce a basic under-

standing of mechanisms.

I hope that readers will find this book helpftil

and useful, and I sincerely hope that this book will

enable doctors to relieve their patients' pain effec-

tively.

The Guide to Use This Book

U nlike traditional textbooks, this book is

edited as a series of topical seminars

given by active researchers. The order of

chapters is topic related, rather than the traditional

layout of the pain textbooks, which is from periphery

to the brain, and from basic to clinic. Most of topics

are selected based on the recent progress as well as

basic discovery at neurobiological levels in terms of

our understanding. Many particular areas related to

pain and analgesia are not covered, in part due to ei-

ther the lack of molecular and cellular understanding

of the process or the limit space.

Therefore, the readers are encouraged to use this

book, together with the classic textbook of Pain (Wall

and Melzeck). If necessary, the basic neuroscience

textbooks are also recommended including the Prin-

ciple of Neural Science (Kandel, Schwartz, Jessell).

Clinical studies are usually well covered in other

pain-related textbooks. However, due to the limitation

of new translational researches, we did not cover the

clinical pain researches. Readers are encouraged to

use the textbook of pain if needed.

Considering the rapid progress in neuroscience

and pain related researches, the readers are highly

recommended to use the PubMed in combination with

this book.

The book is designed to teach basic principles

for pain while introducing the most recent progress in

exploring basic pain mechanism. We will aim at

undergraduate students (late years), graduate students,

post-doc fellows, medical students, nursing students,

and clinical pain fellows. Although the book is fo-

cused on pain, we would like to also teach the stu-

dents to use Pain as a model for investigating brain

mechanisms.

Contents

Major Contributors

Preface

The Guide to Use This Book

Part I Genes, Neurons and Neurotransmission

Chapter 1 Genes and Neurons (Bong-Kiun Kaang) 3 of Neurotransmitter (Lu-Yang Wang) 17

Chapter 2 Synapses: Coupling of Presynaptic Chapter 3 Synaptic Vesicle Cycle at Nerve Terminals

Voltage-gated Ca ^ Channels to Vesicular Release (Ling-Gang Wu, JianhuaXu) 27

Part n Giutamate, Excitatory Transmission and Pain

Chapter 4 Postsynaptic Excitatory Transmission (John F. El-Husseini) 63

MacDonald, Suhas Kotecha, Michael F. Chapter 7 Spinal Glutamate Receptors (Megimiu

Jackson, Michael Beazely) 43 Yoshimura) 85

Chapters Kainate Receptors (ChristopheMuUe) 53 Chapters Glutamate Kainate Receptor in Pain

Chapter 6 Excitatory Amino Acid Neurotransmitter Transmission and Modulation

Regulation (Rochelle Hines, Alaa (MinZhuo) 97

Part in Neuropeptides, ATP, Retrograde Messengers and Opioids

Chapter 9 Neuropeptides (Xu Zhang, LanBao) 109 Chapter 11 Opioid Receptors (ZhizhongZ. Pan) 131

Chapter 10 ATP and Its Receptors in Pain (Terumasa Chapter 12 Retrograde Messengers (Min Zhuo) 145

Nakatsuka, Jianguo G. Gu) 117

Part IV Inhibitory Transmission and Plasticity

Chapter 13 Inhibitory Transmission (Tian-LeXu) -157 Systems (YvesDeKoninck) 169

Chapter 14 Plasticity of Inhibition; GABA/glycine

Part V Postsynaptic Signaling and Gene Regulation

Chapter 15 Protein Kinases and Phosphatases Fine-tune Neuronal Outputs? (Haruhiko

(Ronald A. Merrill, Stefan Strack) 187 Bito, Sayaka Takemoto-Kimura,

Chapter 16 Activity-dependent Gene Regulation: Hiroyuki Okuno) 207

How Do Synapses Talk to the Nucleus and

ii Contents

Chapter 17 Second Messenger Pathways in Pain Rajan Radhakrishnan) 219

(Kathleen A. Sluka, David A. Skyba, Marie K. Chapter 18 Genetic Approaches for the Study of Pain

Hoeger Bement, Katherine M. Audette, (Rohini Kuner) 235

Part VI Peripheral Nociceptor, Amygdala and Fear

Chapter 19 Peripheral Nociceptors (Makoto Modulation (Volker Neugebauer) 265

Tominaga) 247 Chapter 21 Fear Learning (Paul W. Frankland,

Chapter 20 Amygdala—Pain Processing and Pain Sheena A. Josselyn) 281

Part Vn Spinal Plasticity, Reorganization and Chronic Pain

Chapter 22 Silent Glutamatergic Synapses and (Andrew J. Todd, Alfredo

Long-term Facilitation in Spinal Dorsal Horn Ribeiro-da-Silva) 309

Neurons (MinZhuo) 295 Chapter 24 Spinal Microglia in Neuropathic Pain

Chapter 23 Anatomical Changes in the Spinal Dorsal Plasticity (Michael W. Salter) 325

Horn after Peripheral Nerve Injury

Part VI Cortical Plasticity, Reorganization and Amputation

Chapter 25 ACC Plasticity (MinZhuo) 337 System after Injury

Chapter 26 Reorganization of the Sensorimotor (Huixin Qi, Jon H. Kaas) 351

Part DC Endogenous Analgesia and Other Form of Analgesia

Chapter 27 Endogenous Biphasic Modulation Timothy J. Ness) 387

(MinZhuo, GeraldF.Gebhart) 373 Chapter 29 Acupuncture Analgesia (Zhi-QiZhao) 397

Chapter 28 Paradoxical Analgesic and Hyperalgesic Chapter 30 Mechanisms of Opioid Tolerance

Effects of Stress (Meredith Tumbach Robbins, (Zhizhong Z. Pan) 413

Part X Models for Studying Pain and Searching for Pain Killers

Chapter 31 Models in Pain Research (Timothy J. Chapter 33 Whole-cell Patch-clamp Recording

Ness) • 425 in Vivo (Megumu Yoshimura) 459

Chapter 32 Models for Studying Pain and Searching Chapter 34 Basic Mechanisms of Clinically Used

for Pain Killers in Vitro Electrophysiological Drugs (AnnikaB. Malmberg) 469

Studies of Pain

(Peter Goldstein, JianguoGu) 441

Selected References 481

Appendix I Units in Pain Research 485

Appendix II Useful Websites for the Study of Pain 487

Appendix IH List of Scientific Journals Publishing Studies in Pain 489

Appendix IV Fundamental and Innovative Contribution to Understanding of Basic Mechanism of Pain, Analgesia

and Persistent Pain 491

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