Table Of ContentHandbook of Experimental Pharmacology 239
Beverley Greenwood-Van Meerveld
Editor
Gastrointestinal
Pharmacology
Handbook of Experimental Pharmacology
Volume 239
Editor-in-Chief
J.E.Barrett,Philadelphia
EditorialBoard
V.Flockerzi,Homburg
M.A.Frohman,StonyBrook,NY
P.Geppetti,Florence
F.B.Hofmann,Mu¨nchen
M.C.Michel,Mainz
C.P.Page,London
W.Rosenthal,Berlin
K.Wang,Beijing
More information about this series at http://www.springer.com/series/164
Beverley Greenwood-Van Meerveld
Editor
Gastrointestinal
Pharmacology
Editor
BeverleyGreenwood-VanMeerveld
Neuroscience/Physiology
TheUniversityofOklahomaHealthSciencesCenter
OklahomaCity,Oklahoma
USA
ISSN0171-2004 ISSN1865-0325 (electronic)
HandbookofExperimentalPharmacology
ISBN978-3-319-56359-6 ISBN978-3-319-56360-2 (eBook)
DOI10.1007/978-3-319-56360-2
LibraryofCongressControlNumber:2017937312
#SpringerInternationalPublishingAG2017
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Preface
In 1982, two volumes of the Handbook of Experimental Pharmacology edited by
ProfessorGiulioBertaccini,M.D.,addressingMediatorsandDrugsinGastrointes-
tinal Motility I and II were published. In 1993, David R. Brown, Ph.D., edited a
volumeintheHandbookofExperimentalPharmacologyonGastrointestinalRegu-
latoryPeptides.Over20yearslaterthislatestvolumeoftheHandbookofExperi-
mental Pharmacology aims to connect current ideas and concepts about
gastrointestinal (GI) disorders with the search for novel therapeutics. Towards
thisgoal,thefollowingchapterswillprovideatimelystate-of-the-artoverviewof
the GI tract in health and disease, current treatment approaches and ongoing
developments in drug discovery, and their potential for the better treatment of
patients with GI disorders.GI disordersrank among the mostprevalentdisorders,
withthemostcommonincludingesophagealandswallowingdisorders,gastricand
peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel
syndrome (IBS), and inflammatory bowel disease (IBD). Some of these disorders
areorganicinvolvingpathologicaldamagetotheGItractasseeninIBDwhenthe
bowel becomes inflamed and damaged, leading to abdominal pain, diarrhea, and
rectal bleeding. Other GI disorders such as IBS are termed “functional” disorders
because they lack a structural or biochemically defined cause. Recent estimates
suggest that one in four people suffer from a functional bowel disorder and they
represent40%ofGIproblemsseenbyphysicians.Themajorsymptomsofcommon
GIdisordersincluderecurrentabdominalpainandbloating,heartburn,indigestion/
dyspepsia, nausea and vomiting, diarrhea, and constipation. Despite GI disorders
placing a growing burden on today’s healthcare system, many GI disorders are
difficult to diagnose and the symptoms are not effectively managed. In addition,
many patients with GI disorders donotbenefit fromthe currentlyavailable thera-
peutics.Noveleffectivetherapeuticsarethusurgentlyneeded.Currently,thereare
alimitednumberofmedicationsavailableorapprovedtotreatGIdisordersdue,in
part, to a lack of knowledge of the exact mechanisms underlying GI motility,
absorption, secretion, inflammation, and sensation. Although significant gaps in
theunderstandingofGIdisordersstillexist,newtherapiesarelikelytoemergefrom
current research and development. The immune system in the gut is currently
offering a wide variety of therapeutic targets to treat IBD, whereas concepts
that have emerged to treat GI dysmotility, abdominal pain and IBS, include the
v
vi Preface
brain-gut axis linking the nervous system in the GI tract to the CNS. The gut
microbiome is currently an area of active research. Moreover, our understanding
of the gut microbiota remains in its infancy; however major advances linking the
intestinalmicrobiometothebrain-gutaxisarelikelyovertheupcomingyearsand
will offer new therapeutic targets for the development of novel drugs to treat GI
disorders.
IamimmenselygratefultoJamesBarrettforinvitingmetoserveastheEditorof
this volume on Gastrointestinal Pharmacology in the Handbook of Experimental
Pharmacology book series. I would like to thank the editorial staff from Springer
foralltheirsupport.Mostimportantly,thesuccessofthisvolumeonGastrointesti-
nalPharmacologyisduetoeachofmycolleagueswhogenerouslycontributedtheir
expertise and time to preparing such outstanding chapters for this volume of the
Handbook of Experimental Pharmacology. I am indebted to this team of highly
distinguishedleadersintheGIfield.Wehopethatthisvolumeofthehandbookwill
serve as an essential reference to investigators and scholars involved in basic and
clinicalGIresearchaswellasindividualstreatingpatientswithGIdisorders.
OklahomaCity,Oklahoma,USA BeverleyGreenwood-VanMeerveld
Contents
GastrointestinalPhysiologyandFunction. . . . . . . . . . . . . . . . . . . . . . . 1
BeverleyGreenwood-VanMeerveld,AnthonyC.Johnson,
andDavidGrundy
UpperGIDisorders:PathophysiologyandCurrentTherapeutic
Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
HenryP.Parkman
PostoperativeIleus:Pathophysiology,CurrentTherapeutic
Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
N.Stakenborg,P.J.Gomez-Pinilla,andG.E.Boeckxstaens
Constipation:PathophysiologyandCurrentTherapeutic
Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
AmolSharmaandSatishRao
IrritableBowelSyndrome:PathophysiologyandCurrent
TherapeuticApproaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
MichaelCamilleriandAlexanderC.Ford
InflammatoryBowelDisease:PathophysiologyandCurrent
TherapeuticApproaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
BincyP.Abraham,TasneemAhmed,andTauseefAli
GastrointestinalPharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
MiguelSapsandAdrianMiranda
Sex-RelatedDifferencesinGIDisorders. . . . . . . . . . . . . . . . . . . . . . . . 177
DawnK.PrusatorandLinChang
AbnormalBarrierFunctioninGastrointestinalDisorders. . . . . . . . . . 193
RicardFarre´ andMar´ıaVicario
IrritableBowelSyndromeandStress-RelatedPsychiatric
Co-morbidities:FocusonEarlyLifeStress. . . . . . . . . . . . . . . . . . . . . 219
SiobhainM.O’Mahony,GerardClarke,TimothyG.Dinan,
andJohnF.Cryan
vii
viii Contents
NeuroimmuneModulationofGutFunction. . . . . . . . . . . . . . . . . . . . . 247
TerezShea-DonohueandJosephF.Urban,Jr.
TheRoleoftheGastrointestinalMicrobiotainVisceralPain. . . . . . . . 269
KieranRea,SiobhainM.O’Mahony,TimothyG.Dinan,
andJohnF.Cryan
CriticalEvaluationofAnimalModelsofGastrointestinalDisorders. . . 289
AnthonyC.JohnsonandBeverleyGreenwood-VanMeerveld
SerotonergicMechanismsRegulatingtheGITract:Experimental
EvidenceandTherapeuticRelevance. . . . . . . . . . . . . . . . . . . . . . . . . . 319
NatalieTerryandKaraGrossMargolis
CannabinoidReceptorsinRegulatingtheGITract:Experimental
EvidenceandTherapeuticRelevance. . . . . . . . . . . . . . . . . . . . . . . . . . 343
UlrikeTaschler,CarinaHasenoehrl,MartinStorr,andRudolfSchicho
InsightsintotheRoleofOpioidReceptorsintheGITract:
ExperimentalEvidenceandTherapeuticRelevance. . . . . . . . . . . . . . . 363
JamesJ.GalliganandCatiaSternini
GhrelinandMotilinControlSystemsinGIPhysiologyand
Therapeutics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
GarethJ.Sanger,JohnBroad,BridCallaghan,andJohnB.Furness
CentrallyTargetedPharmacotherapyforChronicAbdominalPain:
UnderstandingandManagement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
HansT€ornblomandDouglasA.Drossman
Index. . . . .. . . . .. . . . . .. . . . .. . . . . .. . . . .. . . . .. . . . . .. . . . .. . . 441
Gastrointestinal Physiology and Function
Beverley Greenwood-Van Meerveld, Anthony C. Johnson,
and David Grundy
Contents
1 Introduction................................................................................... 2
2 BasicAnatomyoftheGITract.............................................................. 3
2.1 BasicFunctionsoftheGITract:GIMotility.......................................... 4
2.2 BasicFunctionsoftheGITract:GISecretionandAbsorption...................... 5
2.3 BasicFunctionsoftheGITract:GIBarrierFunction................................ 5
3 NeuralControloftheGITract............................................................... 6
3.1 EntericNervousSystem................................................................ 6
3.2 ExtrinsicInnervationoftheGITract.................................................. 7
3.3 VisceralAfferentSensitization......................................................... 7
3.4 CentralSensitization.................................................................... 8
4 GIPathophysiology........................................................................... 9
4.1 StressandtheGITract................................................................. 10
4.2 GutImmuneSystem.................................................................... 11
4.3 EffectofAgingontheGITract....................................................... 12
5 SummaryandConclusion.................................................................... 13
References........................................................................................ 13
Abstract
Thegastrointestinal(GI)systemisresponsibleforthedigestionand absorp-
tionofingestedfoodandliquids.DuetothecomplexityoftheGItractandthe
B.Greenwood-VanMeerveld(*)
UniversityofOklahomaandVAMedicalCenter,OklahomaCity,OK,USA
e-mail:[email protected]
A.C.Johnson
UniversityofOklahoma,OklahomaCity,OK,USA
e-mail:[email protected]
D.Grundy
UniversityofSheffield,Sheffield,UK
e-mail:D.Grundy@sheffield.ac.uk
#SpringerInternationalPublishingAG2017 1
B.Greenwood-VanMeerveld(ed.),GastrointestinalPharmacology,
HandbookofExperimentalPharmacology239,DOI10.1007/164_2016_118
