Sensory Nerves

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