Innervation of the Mammalian Esophagus

84 Pages·2006·3.108 MB·English

by  W.L. Neuhuber (eds.)

185
Advances in Anatomy
Embryology
and Cell Biology
Editors
F.F.Beck,Melbourne·B.Christ,Freiburg
F.Clascá,Madrid·D.E.Haines,Jackson
H.-W.Korf,Frankfurt·W.Kummer,Giessen
E.Marani,Leiden·R.Putz,München
Y.Sano,Kyoto·T.H.Schiebler,Würzburg
K.Zilles,Düsseldorf
W.L. Neuhuber · M. Raab ·
H.-R. Berthoud · J. Wörl
Innervation
of the Mammalian
Esophagus
With14Figures
123
Prof.Dr.WinfriedL.Neuhuber
Dr.MarionRaab
Dr.JürgenWörl
InstituteofAnatomy
UniversityofErlangen-Nuremberg
Krankenhausstr.9
91054Erlangen
Germany
e-mail:[email protected]
Prof.Dr.Hans-RudolfBerthoud
PenningtonBiomedicalResearchCenter
LouisianaStateUniversitySystem
6400PerkinsRoad
BatonRouge,LA70808
USA
ISSN 0301-5556
ISBN-10 3-540-29205-5 SpringerBerlinHeidelbergNewYork
ISBN-13 978-3-540-29205-0 SpringerBerlinHeidelbergNewYork
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Acknowledgements
Workintheauthors’laboratorywassupportedbyDeutscheForschungsgemein-
schaft SFB 353 B9 and B15 (to W.L.N.), Swiss National Foundation (to W.L.N.),
JohannesandFriedaMarohn-Stiftung,Erlangen(toM.R.andJ.W.)andNIHgrants
DK 47348 and 57242 (to H.R.B.). Special thanks to Sabine Richter (Zurich) and
AndreaHilpertandAnitaHecht(Erlangen)forexcellenttechnicalassistance.
ListofContents
1 Introduction.............................................. 1
1.1 MuscleLayersoftheEsophagus ................................ 2
2 MaterialsandMethods ...................................... 3
2.1 AnterogradeWGA-HRPTracingfromtheNodoseGanglion ............ 3
2.2 AnterogradeDiITracingfromThoracicDorsalRootGanglia ............ 5
3 ExtrinsicInnervation ....................................... 5
3.1 VagalInnervation .......................................... 5
3.1.1 EfferentVagalInnervation .................................... 5
3.1.1.1 NucleusAmbiguus ......................................... 5
3.1.1.2 DorsalMotorNucleus ....................................... 7
3.1.2 AfferentVagalInnervation .................................... 8
3.1.2.1 VagalAfferentStructuresintheTunicaMuscularis ................... 8
3.1.2.2 VagalAfferentInnervationofMucosaandSubmucosa ................ 31
3.1.2.3 CentralProjectionsofVagalAfferentsfromtheEsophagus ............. 34
3.1.2.4 VagalNociceptors .......................................... 36
3.2 SpinalInnervation.......................................... 36
3.2.1 EfferentSpinalInnervation ................................... 36
3.2.2 AfferentSpinalInnervation ................................... 37
3.2.2.1 FunctionalAspects ......................................... 39
3.3 InnervationofEsophagealSphincters ............................ 41
3.3.1 UpperEsophagealSphincter................................... 41
3.3.2 LowerEsophagealSphincter................................... 41
3.4 SwallowingCentralPatternGenerator ............................ 43
3.5 CorticalRepresentationoftheEsophagusinHuman.................. 44
4 IntrinsicInnervation........................................ 45
4.1 GeneralOrganization ....................................... 45
4.2 EntericCoinnervation ....................................... 46
4.2.1 SpatialRelationshipsofVagalandEntericTerminals
andNeurochemicalCoding ................................... 47
4.2.2 ComparativeAnatomyofEntericCoinnervation..................... 48
4.2.3 OntogenyoftheEsophagealNeuromuscularJunction ................. 49
5 FunctionalConsiderations.................................... 51
5.1 GeneralRemarks........................................... 51
5.2 CooperationBetweenExtrinsicandIntrinsicSystems................. 51
VIII ListofContents
6 ConcludingRemarks........................................ 55
References..................................................... 56
SubjectIndex................................................... 75
Abbreviations
(Theabbreviationsapplytoallfigures.)
ACh Acetylcholine
AChE Acetylcholineesterase
AMB Nucleusambiguus
AMBc Nucleusambiguus,compactformation
ASIC Acid-sensitiveionchannels
CGRP Calcitoningene-relatedpeptide
ChAT Cholineacetyltransferase
Co-GOD Cobaltglucoseoxidase
DAB Diaminobenzidine
DEA-NO Diethylamine-NO
DiA 4-(4-Dihexadecyl-aminostyryl)-N-methylpyridiniumiodide
(cid:1) (cid:1) (cid:1)
DiI 1,1-Dioleyl-3,3,3,3-tetramethylindocarbocyaninemethano-
sulfonate
DMPG Deglutitivemotorpatterngenerator
DMX Dorsalmotornucleusofvagusnerve
E Embryonicday
γ
GABA -Aminobutyricacid
GAL Galanin
GERD Gastroesophagealrefluxdisease
GFAP Glialfibrillaryacidicprotein
ICC InterstitialcellsofCajal
IGLE Intraganglioniclaminarending
IMAs Intramusculararrays
LES Loweresophagealsphincter
L-NAME NG-nitro-l-argininemethylester
L-NNA Nω-Nitro-l-arginine
mAChR Muscarinicacetylcholinereceptor
mGluR Metabotropicglutamatereceptor
M-ENK Met-enkephalin
NADPH-d Nicotinamideadeninedinucleotidephosphatediaphorase
NKA NeurokininA
NK-1R Neurokinin-1receptor
NO Nitricoxide
X Abbreviations
nNOS Neuronalnitricoxidesynthase
NONOate [Z]-1-[2-aminoethyl]-N-[2-aminoethyl]diazen-1-ium-1,2-diolate
NPY NeuropeptideY
NT Neurotrophin
NTS Nucleustractussolitarii
NTSce NTSsubnucleuscentralis
NTSim NTSsubnucleusintermedius
NTSis NTSsubnucleusinterstitialis
P Postnatalday
RLN Recurrentlaryngealnerve
SLN Superiorlaryngealnerve
SP SubstanceP
TMB Tetramethylbenzidine
Trk Tyrosinereceptorkinase
TRP Transientreceptorpotential
UES Upperesophagealsphincter
VAChT Vesicularacetylcholinetransporter
VGLUT Vesicularglutamatetransporter
VIP Vasoactiveintestinalpeptide
VMAT Vesicularmonoaminetransporter
WGA-HRP Wheatgermagglutinin-horseradishperoxidaseconjugate
Introduction 1
1
Introduction
Theesophagusisarelativelysimplethoughvitalorgan.Itconsistsofatwo-layered
musculartubewhoselumenislinedbysquamousstratifiedepithelium.Beyondits
roleofpropellingfoodfromthepharynxtothestomachbyapropulsivecontraction
waverepresentingtheesophagealphaseofdeglutition(ConklinandChristensen
1994;Jean2001),itismoreandmorerecognizedasasensoryorganfromwhich
avarietyofrespiratoryandcardiovascularreflexescanbetriggered,thuscooper-
atingwiththelarynxinprotectingthelowerairwaysfromaspiration(Barthélémy
etal.1996;Langetal.2002;Langetal.2001;Loomisetal.1997;Meddaetal.2003).
Inruminants,thereisadditionalantiperistalsisforregurgitation.Duringemesis,
the esophagus is a merely passive conduit except for some antiperistalsis in its
upper part. In the interval between swallows, both oral and aboral ends of the
esophagusaretonicallyclosedbytheupperandloweresophagealsphincters,UES
andLESrespectively,whilethetubularesophagusisflaccidandpartlyfilledwith
air.Despitethisapparentsimplicity,neuronalcontrolofesophagealfunctionsis
quitecomplex.
Esophagealswallowingrequiresthewell-coordinatedopeningoftheUES,oral-
to-aboralperistalsis,andopeningoftheLES.Theseeventsareorganizedbyacen-
tral pattern generator in the brainstem and controlled by vago–vagal reflexes
making the esophagus highly dependent on extrinsic vagal innervation (Bieger
1993;Changetal.2003;ConklinandChristensen1994;Jean2001;Miller1986).In
addition,theesophaguscontains,asallotherorgansofthegastrointestinaltract,
entericgangliaprovidingalocalneuronalnetworkformotilitycontrol(Conklin
and Christensen 1994). Although the esophagus harbors some mucous glands,
and its blood vessels receive both intrinsic and extrinsic innervation, themajor
taskoftheesophagealnervetissueismotilitycontrol.Understandingtheinner-
vation of the esophagus is a prerequisite for successful treatment of a variety of
disorders,e.g.,dysphagia,achalasia,gastroesophagealrefluxdisease(GERD),and
non-cardiacchestpain(Castelletal.2004;Clouseetal.1999;Orlando2003;Orlando
2004;Qualmanetal.1984;StorrandAllescher1999).Inparticular,GERDwithits
highprevalence of more than10% represents a significant health problem. This
reviewaimsatsummarizingcurrentknowledgeofanatomyofesophagealinner-
vationandwillfocusonpeculiaritiesofmotorinnervationofstriatedesophageal
muscle, i.e., enteric coinnervation, and possible involvement of vagal afferent
neuronsinmyentericganglioniccircuitry.Foramoreextensivecoverage,inpar-
ticularoftheolderliteratureandoffunctionalandclinicaldata,thereadermay
consult the classical handbook article by Stöhr (1957) or recent reviews (Chang
etal.2003;ConklinandChristensen1994;Orlando2003;Orlando2004;Sengupta
2000).
The vagus nerve and branches from the sympathetic trunk and the celiac
ganglionprovidemotor,preganglionicparasympathetic,andpostganglionicsym-
patheticinput,andtheseelementsalsocarrynumerousafferentfibersprojecting