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Farmacie

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The evolution in our understanding of Opioid receptors and their subtypes is intimately linked to the development of new pharmacological treatments for diseases and disorders as diverse as addiction, self-injurious behavior, pain, cancer, inflammation, eating disorders, traumatic injury, pruritis and movement disorders. The contributions contained in Opioid Receptors and Antagonists: From Bench to Clinic represent efforts from leading international scientists and clinicians making use of the latest information emerging from the study of the opioid-receptor system. The authors use a variety of experimental and clinical approaches involving the fields of molecular biology, biochemistry, anatomy, pharmacology, behavioral neuroscience and psychiatry to illustrate rapidly developing experimental and therapeutic areas. Highlights include characterization of opioid receptors, chemistry and pharmacology of opiod antagonists for various receptor subtypes (Mu, Kappa, and Delta), discussion of therapeutic uses of opiod antagonists and exploration of innovative approaches to therapeutic drug delivery. Opioid Receptors and Antagonists: From Bench to Clinic offers a comprehensive view of recent work on opiod antagonist applications and uses in various clinical treatments. Emphasis is placed on disorders of the reward system. This volume serves as reference while also illuminating prospects for future research.

Pharmacology. Therapy --- farmacie --- farmacologie --- toxicologie

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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 ChristophSteinandChristianZo¨llner ThePharmacologyofVoltage-GatedSodiumChannels inSensoryNeurones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519 ReginaldJ. DochertyandClareE. Farmer RoleofCalciuminRegulatingPrimarySensory NeuronalExcitability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563 T. D. Gover,T. H. MoreiraandD. Weinreich FutureTreatmentStrategiesforNeuropathicPain. . . . . . . . . . . . . . . . . . . . . . . . 589 FabienMarchand,NicholasG. JonesandStephenB.

Pharmacology. Therapy --- Neuropathology --- farmacie --- farmacologie --- hersenen --- toxicologie

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Cancer has surpassed heart disease as the number one killer in the world, and standard cancer therapy such as radiation, chemotherapy, and surgery may have reached its plateau in further improving the outcome of treated patients. Biological therapies combined with other treatment approaches may be the next X-factor to greatly extend survival time and improve patients' quality of life. One of the most developed fields in biological therapy is immune therapy, which has stemmed into many branches due to its significance and the tremendous effort by a large population of scientists. Tumor-targeted antibody therapy has been successfully used for treating some types of tumors, and the first tumor vaccine against ovarian cancer has been developed for clinical application. Targeted Cancer Immune Therapy provides comprehensive coverage of novel immune therapeutic approaches, including cytokine therapy, engineered cell therapy, and the application of tumor-targeted antibodies for generating tumor-specific cell therapy, TLR ligand therapy, and cytokine therapy. In the section "Cytokine Immune Therapy," the authors review relatively new cytokine family members, such as the IL12 family, IL18, IL21, IL24, IL28, and IL29, in regard to the anti-tumor function and application in treating tumors. The strategy for targeting and retaining cytokines in the tumor microenvironment is also reviewed. The section "Cell-based Immune Therapy" focuses on reviewing "state of the art" approaches for engineering potent immune regulatory or effector cells, such as dendritic cells, T cells, and stem cells, for tumor targeting and initiation of tumor specific immune response. In the section "Targeted Immune Therapy," the authors rearticulate antibody therapy for boosting immune response, which includes immunocytokines, "T-body," and tumor targeted CpG ODN. Some or all of these innovative approaches may ultimately become effective future immune therapies for treating malignancy.

Pharmacology. Therapy --- Oncology. Neoplasms --- farmacie --- farmacologie --- toxicologie --- oncologie

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Optical detection represents the next great horizon for cancer imaging. As molecularly targeted therapeutic agents are delivered to the clinic in increasing numbers, there is a parallel opportunity to advance optical imaging techniques. Because of its limited toxicity and potential for real-time information, optical imaging represents an underdeveloped modality in clinical medicine. Optical Imaging of Cancer: Clinical Applications explores the preclinical and clinical data to support the use of these techniques in cancer imaging. Different fluorescent delivery modalities are explored: from monoclonal antibodies to viral vector delivery. Indications for use include monitoring therapuetic delivery, early detection, and operative removal techniques in all stages of clinical development. This book represents the best and most clinically relevant techniques currently available.

Pharmacology. Therapy --- Oncology. Neoplasms --- farmacie --- farmacologie --- toxicologie --- oncologie