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Role of sensory nerves in disease.- Neuropathic Pain: A Clinical
Perspective.- Visceral Pain: The Neurophysiological Mechanism.-
Migraine.- Afferent Nerve Regulation of Bladder Function in Health
and Disease.- Sensory Nerves and Airway Irritability.- Regulation
of Cardiac Afferent Excitability in Ischemia.- Roles of
Gastro-oesophageal Afferents in the Mechanisms and Symptoms of
Reflux Disease.- Cell and molecular mechanisms regulating sensory
nerve function.- Transient Receptor Potential Channels on Sensory
Nerves.- Acid-Sensitive Ion Channels and Receptors.- Purines and
Sensory Nerves.- Sensory-Nerve-Derived Neuropeptides: Possible
Therapeutic Targets.- Cytokine and Chemokine Regulation of Sensory
Neuron Function.- The Role of Peptides in Central Sensitization.-
Current and Future treatment strategies targeting sensory nerves.-
Opioids and Sensory Nerves.- The Pharmacology of Voltage-Gated
Sodium Channels in Sensory Neurones.- Role of Calcium in Regulating
Primary Sensory Neuronal Excitability.- Future Treatment Strategies
for Neuropathic Pa.
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.
Airways inflammation is a complex biological phenomenon resulting
from the recruitment and activation of numerous cell types. Airways
inflammation contributes to the pathophysiology of airways disease.
An understanding of the mechanisms that regulate inflammatory cell
function is essential for the development of novel
anti-inflammatory drugs for the treatment of common respiratory
diseases such as asthma and COPD. This book provides a collection
of valuable reviews on the major inflammatory cells involved in
airways disease and examines the pharmacology of current
anti-inflammatory drugs used in the treatment of airways disease.
Moreover, an insight into the development of emerging drug
therapies is also highlighted. This book is a must for the library
of any researcher or clinician interested in the pathophysiology of
airways disease.
Airways inflammation is a complex biological phenomenon resulting
from the recruitment and activation of numerous cell types. Airways
inflammation contributes to the pathophysiology of airways disease.
An understanding of the mechanisms that regulate inflammatory cell
function is essential for the development of novel
anti-inflammatory drugs for the treatment of common respiratory
diseases such as asthma and COPD. This book provides a collection
of valuable reviews on the major inflammatory cells involved in
airways disease and examines the pharmacology of current
anti-inflammatory drugs used in the treatment of airways disease.
Moreover, an insight into the development of emerging drug
therapies is also highlighted. This book is a must for the library
of any researcher or clinician interested in the pathophysiology of
airways disease.
A concise, accessible account of pharmacology, covering all the key
concepts you need with no gaps. It can be used either as an
introduction to a topic, or as a revision aid. Big Picture Section
- you can relate detail to the subject as a whole High Return Facts
- fills large gaps in your knowledge. Can be used as a revision
tool. Reinforces the major points Cartoon-strip illustrations - you
can visualise difficult concepts in a step-by-step format -
information is chunked into 'student-friendly' sizes Double-page
overviews - read topic summaries without cross-referencing to other
pages - they're all laid out in one spread!
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