This book highlights the importance of the choroid plexus, which forms the blood-cerebrospinal fluid barrier and is the site of the major production of the cerebrospinal fluid (CSF). The authors show that this barrier is crucial for maintaining important compositional differences between the blood plasma and the CSF. The choroid plexus epithelial cells also prevent the spread of infectious agents and other blood-borne entities to the brain tissue. Chapter topics range from the production of CSF by electrolyte regulation in the choroid plexus, to details on the selectively transporting nature of this barrier. Further, the authors elaborate on the important roles of CSF in sustaining brain health by providing hydration, solutes, and nutrients to the brain tissue. Readers will also learn how CSF circulates signaling molecules within the compartments of the brain and removes waste products from the brain tissue. Elucidating the regulation of these processes in the choroid plexus is not only important for the readers' understanding of normal brain development and function, but is also crucial for resolving a variety of cerebral challenges that lead to brain edema, as well as developing treatments for diseases. The book discusses disease models like hydrocephalus, sleep disorders, and age-related dementia. Its comprehensive coverage makes this volume a valuable resource for researchers in cell and neurophysiology, as well as graduate students of the neurosciences.

The primary purpose of this book and its companion volume The Neuropharmacology of Nicotine Dependence is to explore the ways in which recent studies on nicotine and its role in tobacco addiction have opened our eyes to the psychopharmacological properties of this unique and fascinating drug. While the present volume considers the molecular and genetic factors which influence behavioral responses to nicotine and how these may impact on the role of nicotine in tobacco dependence, the book The Neuropharmacology of Nicotine Dependence focuses on the complex neural and psychological mechanisms that mediate nicotine dependence in experimental animal models and their relationship to tobacco addiction in humans. These volumes will provide readers with a contemporary overview of current research on nicotine psychopharmacology and its role in tobacco dependence from leaders in this field of research and will hopefully prove valuable to those who are developing their own research programmes in this important topic.

Genotoxicity and DNA Repair: A Practical Approach provides a key reference for determining how to analyze the genotoxic activity of molecules or materials and, at the same time, serves as a useful tool for researchers in the Environmental Mutagenesis and DNA Repair fields. Focused on genotoxicity assays recommended by the "OECD guidelines for the testing of chemicals", this volume also covers other useful assays, such as some gene mutation assays, the comet assay in different species and applications, and the SMART assays of Drosophila. For all the assays, the book presents brief theoretical introductions to the topics and updated standard and modified step-by-step protocols to perform them. Special emphasis is placed on the analysis of nanoparticles, including an integrative approach analysis. The DNA Repair section includes several assays that provide information on repair activity in vitro and in vivo, as well as recent applications to study DNA repair in humans, cell cultures, and animal models. As a volume in the Methods in Pharmacology and Toxicology series, the chapters contain the kind of detail and key implementation advice that ensures reproducible results in the lab. Authoritative and invaluable, Genotoxicity and DNA Repair: A Practical Approach aims to aid scientists in their pursuit of forwarding this vital field of study.

With genetic engineering, systems explored in this book now exist allowing for the simple, efficient, and near universally precise genetic manipulation directly in any organism, including the mouse. Herein, these models are applied to a wide field of disease areas, including diabetes, cardiovascular disease, skin disorders, cancer, neurodegenerative and neuromuscular diseases, retinal disorders, as well as various behavioral models. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and fully updated, Mouse Models for Drug Discovery: Methods and Protocols, Second Edition serves to equip the reader with an extensive overview of techniques to utilize the many possibilities of mice in the drug development process.

This second edition is a one-source guide to current information about red blood cell physiology and the action of native and recombinant human erythropoietic factors. Topics in the fields of erythropoiesis, recombinant protein discovery and production, and treatment of patients with anemia due to renal failure, cancer, or chronic diseases are covered. The newest theories in erythropoiesis (receptors, signaling), manufacturing, new formulations, and clinical research are discussed.

This book is of interest to researchers and clinical investigators in academia and biotechnology and pharmaceutical companies, to clinical research associates, clinical monitors, and physician investigators.

Metals: Methylmercury Neurotoxicity and its Uptake Action Across the BloodBrain Barrier (M. Aschner et al.). Neurotoxic Metals and Neuronal Signalling Processes (D. Minnema). Lead Poisoning, Toxocariasis and Pica (P.J. Donovick, R.G. Burright). Nocardia (B.L. Beaman). Toxicants: Neurotoxicity of Polychlorinated Biphenyls (R.F. Seegal, W. Shain). Central Nervous System Plasticity and Pathology Induced by Exposure to Organophosphate Pesticides (D.H. Overstreet, G. Schiller). Silver Ipregnation of OrganophosphorusInduced Delayed Neuropathy in the Central Nervous System (D. Tanaka et al.). Selected Mechanisms of Action: Acute and Chronic Neurodegenerative Disorders Produced by Dietary Excitotoxins (C.F. Zorumski, J.W. Olney). Formation of Excess Reactive Oxygen Species Within the Brain (S.C. Bondy, C.P. LeBel). Legal Issues: Courts, Agencies, and Social Risk Assessment (C.P. Gillette, J.E. Krier) 7 additional articles. Index.

In this Handbook of Experimental Pharmacology on "High Density Lipoproteins - from biological understanding to clinical exploitation" contributing authors (members of COST Action BM0904/HDLnet) summarize in more than 20 chapters our current knowledge on the structure, function, metabolism and regulation of HDL in health and several diseases as well as the status of past and ongoing attempts of therapeutic exploitation. The book is of interest to researchers in academia and industry focusing on lipoprotein metabolism, cardiovascular diseases and immunology as well as clinical pharmacologists, cardiologists, diabetologists, nephrologists and other clinicians interested in metabolic or inflammatory diseases.

The rapidly expanding field of food safety includes many new developments in the understanding of the entire range of toxic compounds found in foods -- whether naturally occurring or having been introduced by industry or food processing methods. This 2e of "Introduction to Food Toxicology" explores these developments while continuing to provide a core understanding of the basic principles of food toxicology.
*New information on:
--Solid-phase extraction, immunoassay, and LC/MS
--Mechanisms of regulation of xenobiotic activation and deactivation
--Developments in the modes of action and impact of natural toxins in food plants
--A comprehensive review of the issues surrounding dioxins
--The function of antioxidants and their toxicological aspects
--Acrylamide, its occurrence, toxicity and regulation on its use
--Phytochemicals, their beneficial effects and the modes of action of this growing group of nutraceuticals from food plants
--Diet and drug interactions

Non-clinical drug safety evaluation, the assessment of the safety profile of therapeutic agents through the conduct of laboratory studies in in vitro systems and in animals, is an essential step in the progress of new pharmaceuticals heading toward the ultimate goal of clinical trials and, eventually, approval. In Drug Safety Evaluation: Methods and Protocols, expert researchers detail a compendium of analytical technologies with a focus on clarity and applicability in real life laboratory practice. These meticulous contributions feature key topics such as acute to chronic general toxicity studies, histopathology studies, reproductive toxicity studies, genotoxicity studies, safety pharmacology studies, investigative toxicity studies, and safety biomarker studies. As a volume in the highly successful Methods in Molecular Biology(TM) series, chapters include brief introductions to their respective subjects, lists of the necessary materials, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and authoritative, Drug Safety Evaluation: Methods and Protocols serves as an ideal guide to this field, helpful to pharmaceutical scientists, toxicologists, biochemists, and molecular biologists as well as scientists from all other disciplines who wish to translate these thorough methods into their own work.

This book approaches the subject from a mechanistic perspective that pitches the language at a level that is understandable to those entering the field and who are not familiar with its common phrases or complex terms. It provides a simple encapsulation of concepts and expands on them. In each chapter the basic concept is explained as simply and clearly as possible without a great deal of detail, then in subsequent sections additional material, exceptions to the general rule, examples, etc., is introduced and built up. Such material was generously supplemented with diagrams; conceptually elegant line diagrams in two or three colors. The artwork was well thought out and able to condense the scientific principles into a novel and visually exciting form. The diagrams encourage browsing or draw the reader to salient points. In addition, the technique of highlighting key concepts in a separate box is used throughout each chapter.

Volumes in this widely revered series present comprehensive reviews of drug substances and additional materials, with critical review chapters that summarize information related to the characterization of drug substances and excipients. This organizational structure meets the needs of the pharmaceutical community and allows for the development of a timely vehicle for publishing review materials on this topic.
The scope of the Profiles series encompasses review articles and database compilations that fall within one of the following six broad categories: Physical profiles of drug substances and excipients; Analytical profiles of drug substances and excipients; Drug metabolism and pharmacokinetic profiles of drug substances and excipients; Methodology related to the characterization of drug substances and excipients; Methods of chemical synthesis; and Reviews of the uses and applications for individual drug substances, classes of drug substances, or excipients.
* Presents comprehensive reviews covering all aspects of drug development and formulation of drugs
* Profiles creatine monohydrate and fexofenadine hydrochloride, as well as five others
* Meets the information needs of the drug development community

Primary care clinicians are called on to care for adolescents in a time with increasing pharmacologic agents that are available in the management of these patients. The emphasis in this book is on the current pharmacologic treatment of common medical disorders in adolescents. Selected topics of practical relevance in adolescent medicine are covered. The goal of this book is to provide a succinct and practical guide specifically written for practicing physicians and allied health professionals who work with adolescents.

Computational methods, and in particular quantum chemistry, have taken the lead in our growing understanding of noncovalent forces, as well as in their categorization. This volume describes the current state of the art in terms of what we now know, and the current questions requiring answers in the future. Topics range from very strong (ionic) to very weak (CH-- ) interactions. In the intermediate regime, forces to be considered are H-bonds, particularly CH--O and OH--metal, halogen, chalcogen, pnicogen and tetrel bonds, aromatic stacking, dihydrogen bonds, and those involving radicals. Applications include drug development and predictions of crystal structure.

Toxins are important virulence determinants responsible for microbial pathogenicity and/or evasion of the host immune response. Understanding the molecular and cellular biology of toxins is critical for the development of new anti-toxin strategies, particularly for those with bioterrorism capability. Indeed, potential applications of toxin research extend beyond simply combating microbial virulence and include the development of novel anti-cancer drugs and other frontline medicines, use of toxins as tools in neurobiology and cellular biology, etc. This timely volume serves as an update on important recent advances. Written by internationally respected scientists, topics reviewed include: toxins carried by mobile genetic elements, botulinum neurotoxins, anthrax, subtilase cytotoxin, Pasteurella multocida toxin, RTX toxins of vibrios, vacA toxin, staphylococcal immune evasion toxins, and fungal ribotoxins. The book is essential reading for everyone with an interest in microbial toxins, and it is recommended for other scientists with an interest in microbiology, bioterrorism, microbial pathogenesis, and microbial genomics.

This volume provides reviews of six topics demonstrating the breadth of the field and recent successes in medicinal chemistry. Each of the first five chapters takes an important biochemical target as its theme and provides an insight into current progress in drug design. The last chapter focuses on the vital subject of pharmacokinetics and the great strides that have been made in this discipline during the past decade. All chapters provide an insight into the skills required of the modern medicinal chemist, in particular, the use of an appropriate selection of the wide range of tools now available to solve key scientific problems.
*Presents the latest research in the field of drug discovery
*Publishes on a twice yearly basis to bring you the most innovative updates in medicinal chemistry
*Available as an online resource via ScienceDirect

This book brings together physicians, scientists and those concerned with the production and use of anti-inflammatory drugs to discuss basic issues affecting all aspects of side-effects, including their detection and treatment. The chapters cover a wide variety of topics including the epidemiology, clinical and experimental aspects of side-effects in the GI tract, liver, kidney, cartilage, bone and skin as well as the problems associated with the newer range of disease-modifying anti-rheumatic drugs such as methotrexate and cyclosporin. This book should be of interest to all those who develop and use anti-inflammatory analgesic drugs, from basic scientists to clinicians. It contains papers presented at the Third International meeting on "Side-Effects of Anti-inflammatory and Analgesic Drugs" held in Verona, Italy, 8-11 May 1991.

The ACMT National Case Conference (NCC) is a monthly discussion of novel or interesting cases in medical toxicology. Participation is through online webinar, and the conferences are recorded to allow for review at any time. The cases in this book are taken from recordings of NCC with edits and revisions by contributors and editors to demonstrate educational points. The majority of the case information is from the original recording and represents actual patient presentations. However, some of the details have been changed and fictional information added to enhance the educational value. This volume covers a broad range of toxicological topics, and specialty guidance is offered at the end of every case to aid non-toxicologists. The dilemmas are applicable to both academic and clinical medicine. A list of relevant questions is also provided for each case. Subjects include common toxicological problems, rare presentations of common problems, common problems with controversial treatments or difficult diagnoses, and rare problems. Case Studies in Medical Toxicology from the American College of Medical Toxicology is a detailed reference text on specific toxicological issues and also serves as a practical review for those taking board exams. As a result, this volume is an important and necessary resource for medical students, residents, and fellows, as well as primary-care physicians, intensivists, and toxicologistsCase Studies in Medical Toxicology from the American College of Medical Toxicology is a detailed reference text on specific toxicological issues and also serves as a practical review for those taking board exams. As a result, this volume is an important and necessary resource for medical students, residents, and fellows, as well as primary-care physicians, intensivists, and toxicologists. All proceeds from this book will be donated to the Medical Toxicology Foundation.

This volume addresses one of the Holy Grails in Psychiatry, namely the evidence for and potential to adopt 'Biomarkers' for prevention, diagnosis, and treatment responses in mental health conditions. It meshes together state of the art research from international renowned pre-clinical and clinical scientists to illustrate how the fields of anxiety disorders, depression, psychotic disorders, and autism spectrum disorder have advanced in recent years.

This groundbreaking book covers every aspect of deadly toxic chemicals used as weapons of mass destruction and employed in conflicts, warfare and terrorism. Including findings from experimental as well as clinical studies, this one-of-a-kind handbook is prepared in a very user- friendly format that can easily be followed by students, teachers and researchers, as well as lay people. Stand-alone chapters on individual chemicals and major topics allow the reader to easily access required information without searching through the entire book.
This is the first book that offers in-depth coverage of individual toxicants, target organ toxicity, major incidents, toxic effects in humans, animals and wildlife, biosensors, biomarkers, on-site and laboratory analytical methods, decontamination and detoxification procedures, prophylactic, therapeutic and countermeasures, and the role of homeland security.
Presents a comprehensive look at all aspects of chemical warfare toxicology in one reference work. This saves researchers time in quickly accessing the very latest definitive details on toxicity of specific agents used in chemical warfare as opposed to searching through thousands of journal articles. Will include the most agent-specific information on the market.
Includes detailed coverage of the most exhaustive list of agents possibly used as chemical warfare agents in one source. Section 4: Agents That Can Be Used as Weapons of Mass Destruction ? 25 chapters long. Other books on the market only include a sample selection of specific agents. Offering all possible agents detailed under one cover makes this appealing to a wider audience and saves researchers time.

The Forward will be written by Dr. Tetsuo Satoh, Chiba University, Japan. He is one of the most respected, recognizable authorities on chemical warfare agents which will set the authoritative tone for the book.

Covers risk to humans, animals and the environment equally. Researchers involved in assessing the risks involved with a possible chemical warfare attack and those who are developing response plans to such attacks must look at not only the risks to human health but to our wildlife and environment as well. The holistic approach taken in this book ensures that the researchers have ready access to the details no matter which aspect of the effects of CWA's they might be concerned with.

Contents

Philip C. Sharpe, Rosemary S. Harrison, and David P. Fairlie: Amyloid Peptides and Proteins in Review. - Marilena Kampa, Artemissia-Phoebe Nifli, George Notas, Elias Castanas: Polyphenols and Cancer Cell Growth. - Michal Janitz: Assigning Functions to Genes The Main Challenge of the Post-Genomic Era. - Brigittte M. Jockusch, Kai Murk and Martin Rothkegel: The Profile of Profilins.

The International Conference of Harmonization (ICH) has worked on har- nizing the stability regulations in the US, Europe, and Japan since the early 1990s. Even though the Stability Guidelines Q1A (R2) was issued over a decade ago, issues surrounding this arena continue to surface as the principles described in the guideline are applied to different technical concentrations. As a result, the stability community has continued to discuss concerns and find ways of harmonizing regulatory requirements, streamlining practices, improving processes in order to bring safe and effective medical supplies to the patients around the world. In 2007, the American Association of Pharmaceutical Scientists (AAPS) Stability Focus Group organized two workshops - the Stability Workshop and the Degradation Mechanism Workshop. These meetings attracted many industry scientists as well as representatives from several regulatory agencies in the world to discuss important topics related to pharmaceutical stability practices. Recognizing the importance of documenting these discussions and with the permission of AAPS, I have worked with speakers to assemble a collection of 30 articles from presentations given at these two meetings, mainly the Stability Workshop. I trust that this book will be beneficial to all of you in providing guidance and up-to-date information for building quality stability programs. v Freedom of our mind is Mother of all inventions.

If you had the chance to heal and live a journey of unimaginable proportions, would you? an odyssey, not unlike Homer's Odyssey in its journey into the fantastical, or the Iliad, which deals with the truth of war in its tragedy and scope. NDMA. A corporate by-product which launches a journey of epic and fantastical proportions, the poison of the NDMA creating a sensory psychic and empath with untold knowledge, a woman who had to become secluded from the world because of her ability to feel atomic energy in the form of people's diseases and the world's pain. never before lived that brings a new understanding that will change the perceptions of 8 billion people with regard to politics, economics, medicine, religion, the environment, law and war. would change the face of life on this planet, would you?

This book summarizes the recent advancements for drug delivery systems (DDS) in terms of fundamental principles, rapidly emerging techniques and developing frontiers of molecular imprinting. Especially with the combination of enantioselective molecularly imprinted polymers and water compatible molecularly imprinted polymers, stimuli responsive imprinted DDS have been innovated and applied to dermal delivery, ophthalmic drugs and cancer treatment. This philosophy comprehensively revolutionizes the treatment strategy of human healthcare and provides the possibility to re-trigger in vivo an exhaust system after the complete release of the starting drug cargo, thus enabling precision medicine. To this end, the following unique features will be discussed and concluded: 1) State-of-the-art definition of MIP as drug delivery systems. 2) Advanced techniques and clinical applications of MIP as drug delivery systems in the past decade. 3) Novel frontiers and brand-new technologies, for example, drug delivery devices for zero-order sustained release and stimuli responsive imprinted DDS. 4) Revolutionary impact on dermal delivery, ophthalmic drugs and cancer treatment. 5) Future challenges and perspectives

Theintentionofthisbookistoprovideacomprehensiveandcontemporaryreview ofthebiologyofsensorynerves. InkeepingwiththethemeoftheHandbookof Experimental Pharmacology series, emphasis will be placed on the actions of drugs,transmittersandautacoidsthatinitiateorinhibitsensorynerveactivation (through actionsonionchannelsandreceptorsattheirperipheralterminals)or modulate the release or actions of the transmitters released from the central terminalsofsensorynerves. Onthebasisofextensivesupportiveevidenceinthe literature, it is our view that many diseases are characterized by alterations in sensorynervefunction(e. g. pain,cardiovasculardiseaseandmigraine). Itisour beliefthatthisbookwillbeunique,asitwillcomprehensivelycovertheroleof sensory nerves across many therapeutic areas. To address directly one of the editorialboardqueries,thisisnotintendedtobeabookaboutthepharmacology ofpain. Thatsaid,tomostpharmacologists,painisthemostobviousindicationfor aroleorsensorynervesindisease. Webelievethatthelessonslearntfromthestudy ofneuropathicpainwillbeinvaluableforresearchersintheothertherapeuticareas covered inthisvolume. Sincemostinterest hasfocusedontheroleofsensory nervesinneuropathicpain,wehaveaddedanumberofchaptersdevotedtothis subject. Thebookisorganizedinthreeparts,coveringthetypesandrolesofsensory nervesinsomaticandvisceraldisorders(PartI),speci?ctargetsonsensorynerves relevanttopainandvisceraldisorders(PartII)andadescriptionofcurrentand futuretherapeuticstrategiesfortargetingsensorynerves(PartIII). The?rsttwochaptersinPartIaredevotedtodescribingtheclinicalfeaturesof neuropathicpainandvisceralpain. Ourintentionisfortheauthorstoprovidea clinicalviewpointonthefeaturesoftheseconditionsandtheadvantages/disadv- tagesofcurrenttreatmentmodalities. Thenext?vechaptersinPartIfocusonthe roleofsensorynervesinotherpathologicalconditions. Severalcommonthemes willemergeinthispart,includingthemodeofsensorynerveactivationinvarious tissues and organs, the alterations in sensory nerve excitability associated with disease,andtheimportanceofin?ammationandin?ammatorymediatorsininiti- ingalteredsensorynervefunctionindisease. v vi Preface Whilstthe?rstpartfocusesontheclinicaland/orsystemsphysiology,PartIIhas itsfocusatthecellandmolecularlevel. Thisparthighlightsthecurrentundersta- ingofproteins/ionchannels/mediatorsthathavecreatedthemostintenserecent interestintheareaofsensorynervebiology. Together,thesechapterswillgivethe reader important knowledge about how sensory nerve function can be altered pharmacologically. Thelastchapterinthispartdescribestheprocessesthatgive risetoalteredneuralre?exesatthecentrallevel. Themechanismsdescribedin thesechaptersreinforcetheroleofproteins/mediatorshighlightedinthepreceding chapters. Theroleofthesecellular,molecularandphysiologicalprocessesinthe diseasesdiscussedinPart1areemphasized. TheaimofPartIIIistohighlightpotentialdrugtargetsthatmightaltersensory nervefunction. Mostoftheworkhasbeendevotedtothetreatmentofneuropathic painandsothispartheavilyemphasizesthissubject. However,aswillbeapparent fromPartI,manyofthesetargetscouldbeutilizedinothertherapeuticareasthat implicatesensorynervesintheirpathophysiologicalprocesses. Thefocusofthe chaptersisonopioidsandmodulatorsofionchannelsandthenthe?nalchapteris devotedtofuturetreatmentstrategiesforneuropathicpain. Finally,wewouldliketothankallthecontributors,includingco-authors,who agreedtowritechaptersforthisbookandthepublishers,especiallySusanneDathe, fortheirpatienceandassistance. Baltimore B. J. Canning London D. Spina Contents PartI RoleofSensoryNervesinDisease NeuropathicPain:AClinicalPerspective ...3 RalfBaron VisceralPain:TheNeurophysiologicalMechanism...31 JyotiN. Sengupta Migraine ...75 SilviaBenemei,PaolaNicoletti,JayG. Capone,Francesco DeCesaris,andPierangeloGeppetti AfferentNerveRegulationofBladderFunctioninHealth andDisease ...91 WilliamC. deGroatandNaokiYoshimura SensoryNervesandAirwayIrritability...139 B. J. CanningandD. Spina RegulationofCardiacAfferentExcitabilityinIschemia...185 Liang-WuFuandJohnC. Longhurst RolesofGastro-oesophagealAfferentsintheMechanisms andSymptomsofRe?uxDisease ...227 AmandaJ. PageandL. AshleyBlackshaw PartII CellandMolecularMechanismsRegulatingSensory NerveFunction TransientReceptorPotentialChannelsonSensoryNerves ...261 S. R. EidandD. N. Cortright Acid-SensitiveIonChannelsandReceptors ...283 PeterHolzer PurinesandSensoryNerves...333 GeoffreyBurnstock vii viii Contents Sensory-Nerve-DerivedNeuropeptides: PossibleTherapeuticTargets ...393 ElizabethS. Fernandes,SabineM. SchmidhuberandSusanD. Brain CytokineandChemokineRegulationofSensory NeuronFunction ...417 RichardJ. Miller,HosungJung,SoniaK. BhangooandFletcherA. White TheRoleofPeptidesinCentralSensitization ...451 V. S. Seybold PartIII CurrentandFutureTreatmentStrategiesTargeting SensoryNerves OpioidsandSensoryNerves ...495 ChristophSteinandChristianZoTheintentionofthisbookistoprovideacomprehensiveandcontemporaryreview ofthebiologyofsensorynerves. InkeepingwiththethemeoftheHandbookof Experimental Pharmacology series, emphasis will be placed on the actions of drugs,transmittersandautacoidsthatinitiateorinhibitsensorynerveactivation (through actionsonionchannelsandreceptorsattheirperipheralterminals)or modulate the release or actions of the transmitters released from the central terminalsofsensorynerves. Onthebasisofextensivesupportiveevidenceinthe literature, it is our view that many diseases are characterized by alterations in sensorynervefunction(e. g. pain,cardiovasculardiseaseandmigraine). Itisour beliefthatthisbookwillbeunique,asitwillcomprehensivelycovertheroleof sensory nerves across many therapeutic areas. To address directly one of the editorialboardqueries,thisisnotintendedtobeabookaboutthepharmacology ofpain. Thatsaid,tomostpharmacologists,painisthemostobviousindicationfor aroleorsensorynervesindisease. Webelievethatthelessonslearntfromthestudy ofneuropathicpainwillbeinvaluableforresearchersintheothertherapeuticareas covered inthisvolume. Sincemostinterest hasfocusedontheroleofsensory nervesinneuropathicpain,wehaveaddedanumberofchaptersdevotedtothis subject. Thebookisorganizedinthreeparts,coveringthetypesandrolesofsensory nervesinsomaticandvisceraldisorders(PartI),speci?ctargetsonsensorynerves relevanttopainandvisceraldisorders(PartII)andadescriptionofcurrentand futuretherapeuticstrategiesfortargetingsensorynerves(PartIII). The?rsttwochaptersinPartIaredevotedtodescribingtheclinicalfeaturesof neuropathicpainandvisceralpain. Ourintentionisfortheauthorstoprovidea clinicalviewpointonthefeaturesoftheseconditionsandtheadvantages/disadv- tagesofcurrenttreatmentmodalities. Thenext?vechaptersinPartIfocusonthe roleofsensorynervesinotherpathologicalconditions. Severalcommonthemes willemergeinthispart,includingthemodeofsensorynerveactivationinvarious tissues and organs, the alterations in sensory nerve excitability associated with disease,andtheimportanceofin?ammationandin?ammatorymediatorsininiti- ingalteredsensorynervefunctionindisease. v vi Preface Whilstthe?rstpartfocusesontheclinicaland/orsystemsphysiology,PartIIhas itsfocusatthecellandmolecularlevel. Thisparthighlightsthecurrentundersta- ingofproteins/ionchannels/mediatorsthathavecreatedthemostintenserecent interestintheareaofsensorynervebiology. Together,thesechapterswillgivethe reader important knowledge about how sensory nerve function can be altered pharmacologically. Thelastchapterinthispartdescribestheprocessesthatgive risetoalteredneuralre?exesatthecentrallevel. Themechanismsdescribedin thesechaptersreinforcetheroleofproteins/mediatorshighlightedinthepreceding chapters. Theroleofthesecellular,molecularandphysiologicalprocessesinthe diseasesdiscussedinPart1areemphasized. TheaimofPartIIIistohighlightpotentialdrugtargetsthatmightaltersensory nervefunction. Mostoftheworkhasbeendevotedtothetreatmentofneuropathic painandsothispartheavilyemphasizesthissubject. However,aswillbeapparent fromPartI,manyofthesetargetscouldbeutilizedinothertherapeuticareasthat implicatesensorynervesintheirpathophysiologicalprocesses. Thefocusofthe chaptersisonopioidsandmodulatorsofionchannelsandthenthe?nalchapteris devotedtofuturetreatmentstrategiesforneuropathicpain. Finally,wewouldliketothankallthecontributors,includingco-authors,who agreedtowritechaptersforthisbookandthepublishers,especiallySusanneDathe, fortheirpatienceandassistance. Baltimore B. J. Canning London D. Spina Contents PartI RoleofSensoryNervesinDisease NeuropathicPain:AClinicalPerspective ...3 RalfBaron VisceralPain:TheNeurophysiologicalMechanism...31 JyotiN. Sengupta Migraine ...75 SilviaBenemei,PaolaNicoletti,JayG. Capone,Francesco DeCesaris,andPierangeloGeppetti AfferentNerveRegulationofBladderFunctioninHealth andDisease ...91 WilliamC. deGroatandNaokiYoshimura SensoryNervesandAirwayIrritability...139 B. J. CanningandD. Spina RegulationofCardiacAfferentExcitabilityinIschemia...185 Liang-WuFuandJohnC. Longhurst RolesofGastro-oesophagealAfferentsintheMechanisms andSymptomsofRe?uxDisease ...227 AmandaJ. PageandL. AshleyBlackshaw PartII CellandMolecularMechanismsRegulatingSensory NerveFunction TransientReceptorPotentialChannelsonSensoryNerves ...261 S. R. EidandD. N. Cortright Acid-SensitiveIonChannelsandReceptors ...283 PeterHolzer PurinesandSensoryNerves...333 GeoffreyBurnstock vii viii Contents Sensory-Nerve-DerivedNeuropeptides: PossibleTherapeuticTargets ...393 ElizabethS. Fernandes,SabineM. SchmidhuberandSusanD. Brain CytokineandChemokineRegulationofSensory NeuronFunction ...417 RichardJ. Miller,HosungJung,SoniaK. BhangooandFletcherA. White TheRoleofPeptidesinCentralSensitization ...451 V. S. Seybold PartIII CurrentandFutureTreatmentStrategiesTargeting SensoryNerves OpioidsandSensoryNerves ...495 ChristophSteinandChristianZollner ThePharmacologyofVoltage-GatedSodiumChannels inSensoryNeurones ...519 ReginaldJ. DochertyandClareE. Farmer RoleofCalciuminRegulatingPrimarySensory NeuronalExcitability ...563 T. D. Gover,T. H. MoreiraandD. Weinreich FutureTreatmentStrategiesforNeuropathicPain...589 FabienMarchand,NicholasG. JonesandStephenB.

This thorough volume delves into antiepileptic drug discovery with a comprehensive collection of innovative approaches for the development of antiepileptic therapies, focusing on novel molecular targets for antiepileptic drugs, computer-aided approaches for the identification of new drug candidates, and therapeutic strategies to overcome refractory epilepsy. The last section illustrates the potential benefits that network pharmacology and rational drug repurposing could bring to the antiepileptic drug discovery community. Written for the Methods in Pharmacology and Toxicology series, chapters include the kind of detailed description and implementation advice to ensure results in the laboratory. Authoritative and practical, Antiepileptic Drug Discovery: Novel Approaches aims to provide medicinal chemists, pharmacologists, and other researchers with the tools need to further explore the study of pharmacoresistant epilepsy and the discovery of new antiepileptic drugs.