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RESEARCHARTICLE Localanesthesiainpigletsundergoingcastration—Acomparativestudytoinvestigatetheanalgesiceffectsoffourlocalanestheticsonthebasisofacutephysiologicalresponsesandlimbmovements AnnaM.Saller 1 ,JuliaWerner ID 1 ,JudithReiser 1 ,SteffanieSenf ID 2 ,PaulineDeffner 2 ,NoraAbendscho¨n 2 ,ChristineWeiß 2 ,JohannesFischer 1 ,AndreaScho¨rwerth 3 ,ReginaMiller 3 ,YuryZablotski 2 ,ShanaBergmann ID 3 ,MichaelH.Erhard 3 ,MathiasRitzmann 2 ,SusanneZo¨ls 2 ,ChristineBaumgartner ID 1¤ * 1CenterofPreclinicalResearch,TechnicalUniversityofMunich,Bavaria,Germany,2ClinicforSwine,CenterforClinicalVeterinaryMedicine,LMUMunich,Bavaria,Germany,3ChairofAnimalWelfare,Ethology,AnimalHygieneandHusbandry,LMUMunich,Bavaria,Germany¤Currentaddress:CenterofPreclinicalResearch,KlinikumrechtsderIsarderTechnischenUniversita¨tMu¨nchen,Munich,Germany*christine.baumgartner@tum.de Abstract
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urrentaddress:CenterofPreclinicalResearch,KlinikumrechtsderIsarderTechnischenUniversita¨tMu¨nchen,Munich,Germany*christine.baumgartner@tum.de Abstract Surgicalcastrationofmalepigletswithoutanalgesiaisapainfulprocedure.Thisprospec-tive,randomizedanddouble-blindedstudyaimedtoevaluatetheanalgesiceffectsoffourdifferentlocalanestheticsforpigletcastrationduringthefirstweekoflife.Intotal,54pigletsaged3to7daysweredistributedinto6treatmentgroups:handling(H);castrationwithoutpainrelief(sodiumchloride,NaCl);andcastrationwithalocalanesthetic:4%procaine(P),2%lidocaine(L),0.5%bupivacaine(B)or20mg/mlmepivacaine(M).Byexcludingstressandfearasdisruptivefactorsviaaminimumanesthesiamodel,allpigletsreceivedindividualminimumalveolarconcentration(MAC)isofluraneanesthesia.Twentyminutesbeforecas-tration,alltreatmentgroupsexceptgroupHreceivedoneinjectionpertestis.Then,0.5mlofalocalanestheticorNaClwasinjectedintratesticularly(i.t.),and0.5mlwasadministeredsubscrotally.Acutephysiologicalresponsestonoxiousstimuliatinjectionandcastrationwereevaluatedbymeasuringbloodpressure(BP),heartrate(HR),cortisol,epinephrine,norepinephrineandchromograninA(CgA);limbmovementswerequantified.Theresultsconfirmthatcastrationwithoutanalgesiaishighlypainful.Surgicalcastrationwithoutpainreliefrevealedsignificantchangesinmeanarterialbloodpressure(MAP)andHR.LocalanestheticadministrationsignificantlyreducedchangesinBPandHRassociatedwithcas-tration.Pigletsreceivingapreoperativelocalanestheticexhibitedthefewestlimbmove-mentsduringcastration,whiletheNaClgroupexhibitedthemost.InjectionitselfwasnotassociatedwithsignificantchangesinMAPorHR.However,manypigletsexhibitedlimbmovementsduringinjection,indicatingthattheinjectionitselfcausesnociceptivepain.Nosignificantdifferenceswerefoundbetweengroupsregardingparametersofplasmacortisol,catecholaminesandCgA.Inconclusion,allfourlocalanestheticsadministeredarehighly
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antdifferenceswerefoundbetweengroupsregardingparametersofplasmacortisol,catecholaminesandCgA.Inconclusion,allfourlocalanestheticsadministeredarehighly PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20201/17 a1111111111a1111111111a1111111111a1111111111a1111111111 OPENACCESSCitation:SallerAM,WernerJ,ReiserJ,SenfS,DeffnerP,Abendscho¨nN,etal.(2020)Localanesthesiainpigletsundergoingcastration—Acomparativestudytoinvestigatetheanalgesiceffectsoffourlocalanestheticsonthebasisofacutephysiologicalresponsesandlimbmovements.PLoSONE15(7):e0236742.https://doi.org/10.1371/journal.pone.0236742Editor:MichaelBader,MaxDelbruckCentrumfurMolekulareMedizinBerlinBuch,GERMANYReceived:March31,2020Accepted:July13,2020Published:July30,2020Copyright:©2020Salleretal.ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.DataAvailabilityStatement:AllrelevantdataarewithinthepaperanditsSupportingInformationfiles.Funding:ThisworkwasfundedbytheGermanFederalMinistryofFoodandAgriculture(BMEL,https://www.bmel.de)basedonadecisionoftheParliamentoftheFederalRepublicofGermany,grantedbytheFederalOfficeforAgricultureandFood(BLE,https://www.ble.de;grantnumber:
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effectiveatreducingsignsofnociceptionduringcastrationunderlightisofluraneanesthesia.However,injectionofalocalanestheticseemstobepainful. Introduction
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effectiveatreducingsignsofnociceptionduringcastrationunderlightisofluraneanesthesia.However,injectionofalocalanestheticseemstobepainful. Introduction IntheEU,morethan100millionmalepigletsarecastratedeveryyeartopreventtheriskofboartaintincarcasses[1].UntilnowinGermany,castrationhastraditionallybeenperformedwithoutanesthesiainthefirstweekoflife,althoughithasbeenscientificallyshownthatsurgi-calcastrationisapainfulprocedure[2,3].Therefore,accordingtotheGermanAnimalWelfareAct,surgicalcastrationofmalepigletslessthansevendaysofagewithoutanesthesiawillbeforbiddenin2021[4].Gonadotropin-releasing-hormone(GnRH)-vaccination,boarfatteningandsurgicalcastrationundergeneralanesthesiaarediscussedasalternativestocastrationwithoutanesthesia.Germanlawalsopermitstheapplicationoflocalveterinarymedicinalproductsthatareabletoeliminatepain[4].However,scientificevidencefortheefficacyoflocalanesthesiaforpainreliefduringcastrationofpigletsisstilllacking.Forthisreason,thediscussionaboutlocalanesthesiaasalegalmethodinGermanyhasresurfaced.Aspainsensitivitycandifferamongdifferentindividuals,itischallengingtoproveuniver-salpaineliminationasrequestedbyGermanlaw.AccordingtotheInternationalAssociationfortheStudyofPain(IASP),painisdefinedas“anunpleasantsensoryandemotionalexperienceassociatedwithactualorpotentialtissuedamage,ordescribedintermsofsuchdamage”[5].Onecomponentofpainisnociception,definedas“theneuralprocessofencodingnoxiousstimuli”whereby“consequencesofencod-ingmaybeautonomic(e.g.,elevatedbloodpressure)orbehavioral(motorwithdrawalreflexormorecomplexnocifensivebehavior)”.Thefourstepsinthedevelopmentoffeelingpainaretransduction,transmission,modulationandperception.Nociceptionmainlyreferstothefirstthreecomponents,lackingtheconsciousawarenessandemotionalcomponentbutincludingallvegetative,glycemicstressresponsesandmotoricreflexresponses,respectively.Inadditiontobehavioralresponsesandvocalizations,physiologicalparameterscanbeasso-ciatedwithpain[6].Acutestress,includingpainandemotionssuchasfearandanger,triggersaseriesofreactionsinthesympatheticnervoussystem[7].Typicalsympatheticreactionsthatcanbemeasuredinpigsareincreasedbloodpressure(BP)andheartrate(HR)andthesecre-tionofcatecholamines(epinephrineandnorepinephrine)[8,9],andmeanarterialbloodpres-sure(MAP)isoneofthemostsensitivenociceptiveparametersinpigs[10].AnotherindicatorofsympatheticactivityischromograninA,aneuroendocrinesecretoryproteinthatisreleasedtogetherwithepinephrineandnorepinephrineandisdescribedasastressmarkerinpigs[11,12].Further,serumcortisollevelscanbemeasuredtodeterminecastration-inducedneu-roendocrinestressreactions[13].Localanestheticsinduceanesthesiabyblockingsodiumchannelsintheperipheralnervesintheareainwhichtheywereadministered.Throughchannelbinding,sodiuminfluxintoneuronsisinhibited,andnoactionpotentialisformed[14].Currentstudiesoncastrationunderlocalanesthesiashowconflictingresults.InastudybyKluivers-Poodtetal.[15],pigletscastratedaftertheadministrationoflidocaineproducedasignificantlylowerincreaseinplasmacortisollevelsthanpigletscastratedaftertheadministrationofmeloxicam.SimilarobservationsweremadebyHanssonetal.[16],whofoundthatthelidocainegroupsproducedsignificantlydecreasedscoresinvocalizationanddefensivemovements.Afurtherstudyin2005showedthatelectroencephalographic,MAPandpulserateresponsestocastration
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nificantlydecreasedscoresinvocalizationanddefensivemovements.Afurtherstudyin2005showedthatelectroencephalographic,MAPandpulserateresponsestocastration Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20202/172817HS016,2817HS013).Thefundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript.Competinginterests:Theauthorshavedeclaredthatnocompetinginterestsexist.
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withoutanalgesiawerelargerthantheresponsestocastrationafterlidocaineinjection[8].Theuseofsubcutaneousandintratesticularprocaineincombinationwithflunixinprovidedsignif-icantlyimprovedpainreliefonthebasisofplasmacortisolandvocalizationparameters[17].Incontrast,otherstudiesmeasurednodifferencesincortisollevels[18,19]whencomparingpigletcastrationafteradministrationoflidocaineandcastrationwithoutanalgesia.Theaimofthisstudywastoinvestigatewhetherlocalanesthesiaisabletoachievetheelimi-nationofnociceptionduringsurgicalcastration.Fourdifferentlocalanestheticswereevalu-atedonthebasisofnociception-relatedphysiologicalparametersandlimbmovements.Differentiatingpainfromemotionssuchasfearorangerischallenginginaconsciouspiglet.Forthisreason,aminimalanesthesiamodelusinglowdosesofisofluranewaschosen.Inthisway,physiologicalreactionscouldbedirectlyassociatedwithnociceptionduringcastration. Materialsandmethods ThestudywasperformedincompliancewiththeEUDirective2010/63/EUforanimalexperi-mentsandtheGermanAnimalWelfareAct(2018).AllprocedureswereapprovedbytheEthicalCommitteeforAnimalExperimentsoftheGovernmentofUpperBavaria,Munich,Germany(ReferenceNumberROB-55.2-2532.Vet_02-19-11). Animals Fifty-fourhybridGermanLandrace/GermanLargeWhitexPietrainmalepigletsaged3to7days(5.3±1.1days)withweightsabove1.4kg(mean:2.09kg±0.4kg)wereincludedinthisstudy.PregnantsowsweretransferredtotheanimalhusbandryunitoftheClinicforSwine(Oberschleißheim,Bavaria,Germany)atleasttwoweeksbeforefarrowing.SowsandpigletswerehousedaccordingtotheGermanOrderfortheKeepingofProductiveAnimalsandtheEUDirective2010/63/EUforanimalexperiments.Noteethclipping,eartagging,ortaildockingwasappliedtothepiglets.Anoralbolusofiron(1mlperpiglet;URSOFERRAN 1
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heEUDirective2010/63/EUforanimalexperiments.Noteethclipping,eartagging,ortaildockingwasappliedtothepiglets.Anoralbolusofiron(1mlperpiglet;URSOFERRAN 1 150mg/ml,SerumwerkBernburgAG,Bernburg,Germany)wasgivenduringthefirsttenhoursoflife.Pig-letsfrom15litterswererandomlyassignedtooneofthesixtreatmentgroups(n=9pergroup). Studydesign Thiswasarandomizedanddouble-blindedexperimentalstudy. Minimalanesthesiaprotocol Tomeasurenociceptionduringinjectionandcastration,aminimalanesthesiaprotocolwasusedtoexcludedisruptivefactorssuchasfearandstress.Theaimoftheprotocolwastokeepthepigletsinahypnoticstatewithanesthesia(stageIIIplaneIaccordingtoGuedel’sclassifica-tion).Eachgroupwasinducedwithadoseof5%isoflurane(IsofluraneBaxtervet.,BaxterDeutschlandGmbH,Unterschleißheim,Germany)inoxygenviaafacialmask.Pigletsbreathedspontaneously,andinspiratoryandexpiratoryisofluranewasassessed(Vamos 1 plus,Dra¨gerMedicalDeutschlandGmbH,Unterhaching,Germany).Followingthenecessarymeasurementpreparations,adequateanestheticdepthwastestedviathetoepinchreflexmethod,andend-tidalisofluranewasmaintainedat1.69±0.3%withaflowof3Lminute -1 oxygen.Thereflexwastriggeredbyclosingasurgicalclamptoamaxi-mumofthefirstlockandforamaximumof5secondsintheinterdigitalspaceofthehindclaw.Tostandardizethepressureasmuchaspossible,thesamepairofclampswasusedbythesametwopersonsthroughoutthestudy.Asinglereactiontothetoepinch,intheformofaslightwithdrawalofthehindlimb,wasevaluatedasappropriateanestheticdepth.Ifno Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20203/17
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reactionoccurredatall,theisofluraneconcentrationwasreducedby0.2%,andafterthreeminutes,anothertoepinchwasappliedtotheoppositehoof.Prolongedpaddlingandmove-mentoftheforelimbs,backorheadwereassessedasovershootingreactions,andisofluranewasincreasedby0.2%.Subsequenttoadjustmentofthedepthofnarcosis,injectionstartedafterathree-minutewaitingperiod.Inthecaseofpigletsmovingduetofixationforinjectionorcastration,isofluranewasincreasedby0.2%,andtwominutespassedbeforetheinterven-tionwasstarted.Fourminutesaftercastration,anadditionaltoepinchreflexwastestedtover-ifythestateofanesthesia.Anesthesiawasmaintainedover90minutestocollectbloodsamplesbeforethepigletwaseuthanizedwithanintravenousoverdoseofpentobarbital(Euthadorm500mg/mlInjektionslo¨sung,CPPharma,Burgdorf,Germany),andthespinalcordwasremovedforfurtherstudy.AnoverviewoftheexperimentalsetupisshowninFig1. Localanesthesiaandcastration Animalswererandomlyassignedtothesixtreatmentgroups.Thepersonsinvolvedweredou-ble-blinded.Allpiglets,exceptthehandlinggroup(H),receiveda0.5-mlintratesticularand0.5-mlsubscrotalinjection20minutespriortocastration.Procainehasthelongestonsettimemdash;20minutes—ofalltestedlocalanesthetics;thus,thistimewaschosentoensurecomparabilityamongallexperimentalgroups.Anautomaticself-filling1-mlsyringe(HSWECO-MATIC 1 ,Henke-Sass,WolfGmbH,Tuttlingen,Germany)witha25Gcannula Fig1.Overviewoftheexperimentalsetup.Thesymbol indicatesthecollectionofbloodsamples.Baselinebloodsamplesforallfourbloodparametersweretaken5minutesaftertheimplementationofthemeasurements.Bloodsamplesfortheanalysisofepinephrineandnorepinephrineweretaken1minuteafterinjectionand1minuteafterthecuttingofthespermaticcord.ForcortisolandchromograninA(CgA)measurements,bloodsampleswerecollected20and40minutesafterthecuttingofthespermaticcord.Thesymbol
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tingofthespermaticcord.ForcortisolandchromograninA(CgA)measurements,bloodsampleswerecollected20and40minutesafterthecuttingofthespermaticcord.Thesymbol indicatesatissuedamageevent(injection,skinincisionorcuttingofthespermaticcord). showsamoredetailedoverviewofthetimepointsofthemeasurementsofBP,HRandlimbmovementsduringanevent.https://doi.org/10.1371/journal.pone.0236742.g001 Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20204/17
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(0.5x16mm,B.BraunTravaCareGmbH,Hallbergmoos,Germany)wasusedforinjection.Theinjectionsincludedprocainehydrochloride4%(P,procaine)(procainehydrochloride4%—VMD,V.M.D.sa,Arendonk,Belgium),lidocainehydrochloride2%(L,lidocaine)(Xyloci-tin 1 2%,MibeGmbHArzneimittel,Brehna,Germany),bupivacainehydrochloride0.5%(B,bupivacaine)(Bupivacain0.5%JENAPHARM,MibeGmbHArzneimittel,Brehna,Germany)andmepivacainehydrochloride(M,mepivacaine)(Mepidor 1 20mg/mlsolutionforinjectionforhorses,RichterPharmaAG,Wels,Austria).Asapositivecontrol,onegroupreceivedinjec-tionswithonlysodiumchloride0.9%beforecastration(NaCl,castrationwithoutpainrelief).Asanegativecontrol,anothergroupunderwentsimulatedinjectionandcastration(H,han-dling).Surgicalcastration(groupsP,L,B,M,NaCl)wasperformedusingtwoverticalscrotalincisions.Toevaluatethenoxiousstimulusofskinincisionandthenoxiousstimulusofcuttingthespermaticcordseparately,aperiodof2minutesforstabilizationofhemodynamicparame-terswasprovidedbeforethespermaticcordoftherightandlefttesticlewereseveredusinganemasculator.PigletsingroupHwereonlypreparedforcastrationwithouttheoccurrenceofanypainfulprocedure.Isofluraneanesthesiaandpreparationsandmeasurements(bloodparameters,BP,HR,movements,etc.)werecarriedoutasintheotherexperimentalgroups.TheonlydifferenceingroupHwasthatinjectionandcastrationwereonlysimulated.Moreprecisely,handlingofthepigletswasperformedbyonepersonforinjectionandcastration.Insteadofperforminganinjection,thetestiswasjustfixedandgentlytouchedwithaneedlecap.Castrationwassimulatedbyfixingthetestisandgentlytouchingitwiththebluntbackofthescalpelhandle(castration). Measurements
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dandgentlytouchedwithaneedlecap.Castrationwassimulatedbyfixingthetestisandgentlytouchingitwiththebluntbackofthescalpelhandle(castration). Measurements Implementationofphysiologicmeasurements.Inthisstudy,itwasassumedthatallpig-letsexperiencedsimilarstressfromtheinductionprocedureandtheestablishmentofthemea-surements.Twentyminutesbeforeanestheticinduction,alocalanestheticcream(Emla 1 ,AstraZeneceaGmbH,Wedel,Germany)wasappliedtothepiglet’sventralnecktonumbtheskinfortheestablishmentofvenousandarterialaccess.Afteranestheticinduction,pigletswereplacedinasupinepositionontheheatedground.Eyeointment(BepanthenAugen-undNasensalbe,BayerVitalGmbH,Leverkusen,Germany)wasadministered,andcottonwoolwasplacedintheexternalauditorycanaltominimizephysiologicalreactionstobackgroundnoises.OxygensaturationandHRweremeasuredviaapulseoximeter(2500AVET,NoninMedicalInc.,Plymouth,MN,USA)placedatthebaseofthepiglet’stail.Bodytemperaturewasrecordedwiththehelpofarectaltemperatureprobeandremainedconstantbyprovidinganadditionalheatsupply.Respiratoryfrequencyandend-tidalcarbondioxideweremonitoredbycapnometry(Vamos 1 plus,Dra¨gerMedicalDeutschlandGmbH,Unterhaching,Germany)viaabreathingfilterconnectedtothemask.Skinatthearterialandvenousaccesssitewasinjectedwithamaximumof0.3mllidocaine(lidocaine2%,bela-pharmArzneimittelfabrik,Vechta,Germany).Theleftcarotidarteryandjugularveinwerevisualizedwithgentleprepara-tion,andacatheter(3F,Baltextrusion,Montmorency,France)wasintroducedtobothvessels.ForinvasiveBPmeasurement,amicrotipcatheter(SPR-407Mikro-Tip 1
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prepara-tion,andacatheter(3F,Baltextrusion,Montmorency,France)wasintroducedtobothvessels.ForinvasiveBPmeasurement,amicrotipcatheter(SPR-407Mikro-Tip 1 ,Millar,Inc.,Hous-ton,TX,USA)wasplacedinthecarotidartery.Beforeeachmeasurement,thecatheterwascal-ibrated.Therefore,thetipofthecatheterwasplacedjustbeneaththesurfaceofawaterbaththatwasheatedtothepiglet’sbodytemperature(39˚C).Systolic,diastolicandMAPandanelectrocardiogram(ECG)wererecordedcontinuouslywithappropriatehardwaremodulesandcorrespondingsoftware(PLUGSYSmodule,TransducerAmplifiermoduleTAM,heartratemodule,HAEMODYNsoftware,HugoSachsElektronik–HarvardApparatusGmbH,March-Hugstetten,Germany).Baselinevalueswerecollectedoveroneminutepriortothe Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20205/17
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“injection”and“castration”events.MeanvaluesandstandarddeviationsofBPandHRwerecalculated.Subsequently,withinoneminuteaftereveryevent,themaximumchangefrombaselinewasselected,andthepercentdeviationfrombaselinewasdetermined.Bloodsamples.Tomaintainhydration,acrystalloidintravenousinfusion(SterofundinIso,B.BraunMelsungenAG,Melsungen,Germany)wasadministeredatarateof4ml/kg/h,andtheextractedbloodvolumewasdirectlysubstituted.Bloodsamples(max.1.8mleachsam-ple)weretakenviathevenousportatthefollowingtimepoints.Baselinevaluesforallparame-tersweretakenfiveminutesafterplacementofthecathetersandpriortothefirsttoepinchreflextest.Fortheanalysisofcatecholamines,EGTA-plasmatubeswereprechilledonice.Sampleswerecollectedoneminuteafterinjectionandoneminuteaftercuttingthespermaticcord.SerumsamplesforcortisolandCgAweretaken20and40minutesaftercastration(cut-tingofthespermaticcord).Bloodsamplesforcatecholamineswerecentrifuged(5minutes,3000U/min,4˚C)immediatelyaftercollection.Serumsampleswerestoredforonehouratroomtemperaturebeforecentrifugation(10minutes,3000U/min,4˚C).Collectedplasmasampleswerestoredat-80˚C,andserumsampleswerestoredat-20˚Cuntilanalysisbyacer-tifiedlaboratory.Limbmovements.Duringinjection,incisionandspermaticcordtransection,eachpigletwasimmobilizedbythesameperson,whoheldthepigletinasupinepositionwithbothhandsunderthebackandthehindquarters.Thisensuredthatboththemovementsofthefourlimbsandtensionofthebackcouldbeperceivedandassessed.Inaddition,eacheventwasfilmedandevaluated.Toassessthequalityoflimbmovementsforeverypigletandevent,aspecificscorewasestablishedbasedonBerchtoldetal.[20]andHugetal.[21].Bothfrontandhindlimbsaswellasthespine/backwereassessedindividuallyforeachtesticle.Amaximumscoreof28points(14pointspertesticle)couldberecordedperevent(injection,skinincision,cut-tingofthespermaticcord)(Table1).Statisticalanalysis.Forthestatisticalanalysis,groupsweretestedforchangesinBPandHR,ageandweightatcastration.ThedistributionofallcontinuousparameterswastestedusingtheShapiro-Wilknormalitytest.Forallnormallydistributedparameters,aparametricone-wayANOVAtestwasperformed.Pairwiset-testcomparisonsbetweengroupswithpost-hocBonferronicorrectionsformultipletestingfollowedbyANOVA.Fornonnormallydis-tributedparameters,aKruskal-Wallistestwasperformed.PairwiseWilcoxontestsforcompar-isonsbetweenparameterswithpost-hocBonferronicorrectionsformultipletestingwere
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arameters,aKruskal-Wallistestwasperformed.PairwiseWilcoxontestsforcompar-isonsbetweenparameterswithpost-hocBonferronicorrectionsformultipletestingwere Table1.ScoringsystemadaptedfromBerchtold[20]andHugetal.[21]toassesspainduringcastrationonthebasisoflimbmovements.Limbscore(eachlimbisscoredseparately)Numberofmovements0Noreaction1Onemovement2Twotothreemovements3Morethanthreemovements,long-lastingmovementsHighestlimbscorepertesticle12Back/spinescoreNumberofmovements0Noreaction1Musclecontraction2MovementsHighestback/spinescorepertesticle2Maximumscorepertesticle:14Maximumscoreperevent:28https://doi.org/10.1371/journal.pone.0236742.t001 Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20206/17
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followedbytheKruskal-Wallistest.Bloodparameterswereanalyzedusingamixed-effectsmodelduetothepresenceofrepeatedmeasures.Bloodparameterdatawerelog-transformedpriortoanalysisduetononnormallydistributedandheteroscedasticresiduals.Pairwisecom-parisonsoffactorcombinationsinthemixed-effectsmodelwereconductedviaestimatedmar-ginalmeanswithposthocBonferronicorrections.Statisticalsignificancewasconsideredatp 0.05.AllstatisticalanalyseswereperformedusingRversion3.6.1(2019-07-05)[22]. Results Themean±standarderrorofthemean(SEM)bodyweightsofthepigletsineachtreatmentgroupwereasfollows:H:2.2±0.5;NaCl:2.1±0.6;P:1.8±0.3;L:2.5±0.5;B:2.1±0.4;andM:2.2±0.4kg.Themean±SEMagesofthepigletsineachtreatmentgroupwereasfollows:H:5.3±1.2;NaCl:4.9±1.3;P:5.1±1.2;L:5.3±1.4;B:5.6±1.0;andM:5.5±1.0days.Meanbodyweightandagedidnotsignificantlydifferbetweenthetreatmentgroups. Bloodpressure
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±1.2;NaCl:4.9±1.3;P:5.1±1.2;L:5.3±1.4;B:5.6±1.0;andM:5.5±1.0days.Meanbodyweightandagedidnotsignificantlydifferbetweenthetreatmentgroups. Bloodpressure ThemeanMAPofallpigletswas55.68±7.15mmHg.Fig2showsthemeanofthemaximumchangesinMAPafterinjection,skinincisionandcuttingofthespermaticcordineachtreat-mentgroup.Duringinjection,nosignificantdifferenceamongthegroupswasdetected.LocalanestheticgroupsP(p<0.001),L(p<0.001),B(p<0.001)andM(p<0.001)showedstatis-ticallysignificantreductionsinmaximumMAPchangescomparedtotheNaClgroupafterskinincision.ThedeviationfrombaselineintheNaClgroupwas24%.ThiswasthehighestvalueobservedduringskinincisionandwasalsosignificantlydifferentfromthatintheHgroup(p<0.001).RegardingcuttingofthespermaticcordinlocalanestheticgroupsP(p<0.001),L(p<0.001),B(p<0.001)andM(p<0.001),thedeviationinthemaximumMAPchangewassignificantlydecreasedcomparedtothatintheNaClgroup.BetweenthelocalanestheticgroupsandcomparedtotheHgroup,nosignificantdifferencewasdetected.Similartoskinincision,NaClhadthehighestvalue(45%)aftercuttingthespermaticcordandwassignificantlyincreasedcomparedtoH(p<0.001). Heartrate NosignificantdifferencesinHRdeviationweredetectedamongthetreatmentandcontrolgroupsafterinjection.TheHRafterskinincisioningroupMwassignificantlydecreasedcom-paredtothatingroupNaCl(p<0.001).TherewasnosignificantdifferenceinthemeanHRamongtheothergroups.Ingeneral,ahighlysignificantchangeinHRfrombaselineaftercut-tingofthespermaticcordwasdiscoveredingroupsP(p<0.001),L(p=0.002),B(p<0.001)andM(p<0.001)comparedtothatingroupNaCl.Additionally,NaClwasassociatedwithasignificantincreasecomparedtoH(p<0.001)(Fig2). Bloodsamples
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0.002),B(p<0.001)andM(p<0.001)comparedtothatingroupNaCl.Additionally,NaClwasassociatedwithasignificantincreasecomparedtoH(p<0.001)(Fig2). Bloodsamples Cortisol.Plasmacortisolconcentrationsinpigletsattimepointsbeforesurgicalcastrationand20and40minutesaftercastrationareshowninTable2.Comparisonamongtheexperi-mentalgroupsrevealednosignificantdifferencesinplasmacortisolconcentrationsatanytimepoint.Withinthegroups,20(H:p<0.001,NaCl:p<0.001,P:p<0.001,L:p<0.001,B:p<0.001,M:p<0.001)and40(H:p<0.001,NaCl:p<0.001,P:p<0.001,L:p<0.001,B:p<0.001,M:p<0.001)minutesaftercastration,increasedcortisollevelscomparedtobase-linelevelsweremeasured. Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20207/17
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Fig2.Percentchangeinmeanarterialbloodpressure(MAP)andHeartRate(HR).Twentyminutespriortocastration,a0.5-mli.t.injectionanda0.5-mlsubscrotalinjectionwereadministeredineachtestis.Thesixbarsillustratethemaximumpercentchangefrombaselinewithin1minuteafterinjection(A,D),skinincision(B,E)andcuttingofthespermaticcord(C,F)inthedifferentexperimentalgroups.Handling=noinjectionandnocastration,onlysimulationoftheprocedures;NaCl=injectionofsodiumchloride(NaCl)andcastration;Procaine=injectionof Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20208/17
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Catecholamines.EpinephrineandnorepinephrineconcentrationsinpigletsmeasuredbeforecastrationaswellasoneminuteafterinjectionandcastrationareshowninTable3.Nosignificantdifferenceswerefoundamongthegroupsatanytimepoint.Baselinemeasure-mentsforbothepinephrineandnorepinephrinegreatlydifferedamongtheexperimentalgroups.Asignificantincreaseinepinephrinefrombaselinetocastration(H:p<0.001,NaCl:p<0.001,P:p<0.001,L:p<0.001,B:p<0.001,M:p<0.001)andinjectiontocastration(H:p<0.001,NaCl:p<0.001,P:p<0.001,L:p<0.001,B:p<0.001,M:p<0.001)wasmeasuredwithinallgroups.Nosignificantdifferenceswerefoundinnorepi-nephrinemeasurements.ChromograninA.PlasmaCgAconcentrationsinpigletsattimepointsbeforesurgicalcastrationand20and40minutesaftersurgeryareshowninTable4.Noneofthemeasure-mentsamongthegroupsatanytimepointweresignificant.Limbmovements.Duringinjection,Bscoredhighest(5.6),followedbyP(4.2),M(3.4),L(2.4)andNaCl(1).Duringskinincision,theNaClgrouphadthehighestscore,with5.6points procaine4%andcastration;Lidocaine=injectionoflidocaine2%andcastration;Bupivacaine=injectionofbupivacaine0.5%andcastration;Mepivacaine=injectionofmepivacaine2%andcastration.Valuesshownaremeans±SEMs.Statisticalsignificanceisindicatedby p 0.05, p<0.01, p<0.001;n.s.=nosignificanceamonggroups.https://doi.org/10.1371/journal.pone.0236742.g002 Table2.Influenceoftreatmentonserumcortisolconcentrations20and40minutesafterthecastrationofpiglets.HandlingNaClProcaineLidocaineBupivacaineMepivacaineCortisol( g/L)Baseline65±19.2471.44±35.7367.22±14.2572.56±28.0667.56±21.5668.00±13.4820mp.castr.104.78±25.40 92.89±32.79 98.11±31.03 101.33±34.67 107.33±27.73 97.89±19.90 40mp.castr.108.89±24.06 91.78±40.90 89.00±33.82
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5.40 92.89±32.79 98.11±31.03 101.33±34.67 107.33±27.73 97.89±19.90 40mp.castr.108.89±24.06 91.78±40.90 89.00±33.82 105.44±35.96 110±33.31 98.78±27.03 Mean±SEMserumcortisolconcentrations( g/L)areshownforthedifferenttreatmentgroups.Valuesshownaremeans±SEMs.Astatisticallysignificantchangefrombaselineisindicatedby p 0.05, p<0.01, p<0.001,n.s.=nosignificance.https://doi.org/10.1371/journal.pone.0236742.t002 Table3.Influenceoflocalanesthesiaonplasmacatecholaminesaftertheinjectionandcastrationofpiglets.HandlingNaClProcaineLidocaineBupivacaineMepivacaineEpinephrine(ng/L)Baseline199.67±142.83126.56±75.43114.11±67.65174.33±161.30153.67±88.31107.67±62.02Injection230.44±197.80n.s.113.89±69.39n.s.103.89±48.65n.s.129.44±103.60n.s.165.13±86.84n.s.115.00±67.25n.s.Castration262.11±237.10 ◆◆◆142.11±105.42 ◆◆◆245.33±155.45 ◆◆◆237.44±240.70 ◆◆◆185.56±106.41 ◆◆◆207.33±175.51
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s.115.00±67.25n.s.Castration262.11±237.10 ◆◆◆142.11±105.42 ◆◆◆245.33±155.45 ◆◆◆237.44±240.70 ◆◆◆185.56±106.41 ◆◆◆207.33±175.51 ◆◆◆Norepinephrine(ng/L)Baseline359±250.74244.33±152.34435.67±263.52424.22±423.93284.78±157.33204.11±164.79Injection436.89±405.26n.s.273.78±152.32n.s.383.44±205.71n.s.341.67±361.57n.s.430,625±382.24n.s.242.00±279.25n.s.Castration341.56±246.52n.s.263.67±88.61n.s.620.89±422.36n.s.349.11±405.10n.s.420.67±406.96n.s.231.78±217.45n.s.Mean±SEMplasmaepinephrineandnorepinephrineconcentrations( g/L)areshownforthedifferenttreatmentgroups.Baselinebloodsamplesweretaken5minutesafterplacementofthecatheters.Theremainingsamplesweretaken1minuteafterinjectionandcuttingofthespermaticcordineachcase.Valuesshownaremeans±SEMs.Astatisticallysignificantchangefrombaselineisindicatedby p 0.05, p<0.01, p<0.001,n.s.=nosignificance.Astatisticallysignificantchangefrominjectionisindicatedby◆p 0.05,◆◆p<0.01,◆◆◆p<0.001,n.s.=nosignificance.https://doi.org/10.1371/journal.pone.0236742.t003 Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,20209/17
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onaverage,followedbytheM(0.3)andP(4.2)groups.IntheLandBgroups,nolimbmove-mentswereregistered.Afterthespermaticcordwascut,theNaClgroupreachedascoreof8.4,andthePgrouphadascoreof0.2.TheL,BandMgroupsdidnotmoveatall(Fig3).Duringinjection,twopigletsintheNaClgroupmoved,whilenopigletsintheHgroupshowedsignsoflimbmovements.Thepigletsinjectedwithalocalanestheticmovedmoreoften(P:n=4;L:n=6;B:n=5;M:n=6)thanthoseinthecontrolgroups.SkinincisionpromptedmovementsonlyinpigletsintheNaCl(n=5),P(n=1)andM(n=1)groups.Sim-ilarly,duringthecuttingofthespermaticcord,thehighestnumberofpigletsshowinglimbmovementswasobservedintheNaClgroup(n=6).AsidefromonepigletinthePgroup,nolimbmovementsweredetectedinpigletsintheotherexperimentalgroups. Discussion
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limbmovementswasobservedintheNaClgroup(n=6).AsidefromonepigletinthePgroup,nolimbmovementsweredetectedinpigletsintheotherexperimentalgroups. Discussion Thepresentstudyreconfirmedthatsurgicalcastrationisahighlypainfulmethod[23,24].Aminimalisofluraneanesthesiamodelwasusedtoassessacutephysiologicalalterationstovali-datetheanalgesiceffectsoffourlocalanestheticsduringcastration.Asnociception-relatedparameters,invasiveBPandHRaswellasbloodconcentrationsofcortisol,epinephrine,norepinephrineandchromograninAweremeasured.Inaddition,limbmovementsofthepig-letswerestudied.Aspain-relatedphysiologicalresponsesareeasilyinfluencedbystressandfear,itisdifficulttodiscriminatepainfromhandlingstress[7].Therefore,tomeasurepurenociception,lightisofluraneanesthesiawasadministered.Isofluraneisavolatileagentwithnoanalgesiceffectsatlowdosages.Evenifithasmoderatecardiodepressiveeffects,intheclinicalrange,isofluraneshowsnoinfluenceonthemagnitudeofBPorHRchangesinresponsetonoxiousstimuli[25,26].Therefore,theuseofisofluranehasalowimpactonstudy-ingnociception.OurresultsshowedthatlocalanesthesiasignificantlyreducedBPandHRchangesafterskinincisionandcuttingofthespermaticcordcomparedtocastrationwithoutanypainmedi-cation.MAPwasthemostsignificantparameterassociatedwithnoxiousstimuliduringcastra-tion.ThisfindingisinlinewithastudythatobservedthatMAPwasthemostsensitivenociceptiveindicatorforpigsunderisofluraneanesthesia[10].HagaandRanheim[8]foundsimilarresultswhenmeasuringinvasivearterialBPduringcastrationwithlidocaineperformedunderhalothaneanesthesia.Duringallthreestepsofthecastrationprocedure,Hinducedmin-imalBPchangesthatwereintherangeofnormalBPfluctuations.Mostnotably,BPchangesinthefourlocalanestheticgroupswerecomparabletothechangeintheHgroup.Thissug-geststhatlocalanesthesiareducesnociceptioninducedbysurgicalcastrationtoalevelofunpleasantnesssimilartothatfeltbypigletshandledintheinguinalregionunderisofluraneanesthesia.CastrationwithoutanypainreliefprovokedthehighestincreaseinBP.Bovaetal.[27]determinedthatifaBPincreaseofmorethan20%occursduringsurgicalintervention,relevantpainmustbeassumed,andrescueanalgesiamaybenecessary.IntheNaClgroup,BP
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]determinedthatifaBPincreaseofmorethan20%occursduringsurgicalintervention,relevantpainmustbeassumed,andrescueanalgesiamaybenecessary.IntheNaClgroup,BP Table4.InfluenceoftreatmentonserumCgA20and40minutesafterthecastrationofpiglets.HandlingNaClProcaineLidocaineBupivacaineMepivacaineChromograninA( g/mL)Baseline0.90±0.390.68±0.250.97±0.610.73±0.250.96±0.630.88±0.5320mp.castr.1.28±1.44n.s.0.66±0.26n.s.0.65±0.45n.s.0.72±0.26n.s.0.73±0.46n.s.0.94±0,70n.s.40mp.castr.0.85±0.28n.s.0.63±0.11n.s.0.57±0.29n.s.0.80±0.33n.s.0.78±0.50n.s.0.87±0.53n.s.Mean±SEMserumCgAconcentrations( g/L)areshownforthedifferenttreatmentgroups.Baselinebloodsamplesweretaken5minutesafterplacementofthecatheters.Valuesshownaremeans±SEMs.Astatisticallysignificantchangefrombaselineisindicatedby p 0.05, p<0.01, p<0.001,n.s.=nosignificance.https://doi.org/10.1371/journal.pone.0236742.t004 Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,202010/17
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Fig3.Limbmovementscoresduringinjection,skinincisionandcuttingofthespermaticcord.Limbmovementswereobservedduringinjection(A),skinincision(B)andcuttingofthespermaticcord(C).Thescorewasappliedtoanalyzetheintensityoflimbmovements:handling=neitherinjectionnorcastration,onlysimulationoftheprocedures;NaCl=castrationwithoutpreoperativeanalgesia;procaine,lidocaine,bupivacaine,andmepivacaine=castrationunderpreoperativelocalanesthetic.https://doi.org/10.1371/journal.pone.0236742.g003 Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,202011/17
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increasedby24%duringskinincision,andanaverageincreaseof45%wasobservedwhilecut-tingthespermaticcord.Botheventshavetobeconsideredhighlypainful,anditwasrecon-firmedthatmanipulatingandcuttingthespermaticcordisthemostpainfulpartofcastration[28].Inapproximatelyhalfoftheanimals,asthemaximumdeviationfrombaseline,adecreaseinBPandHRwasobservedinresponsetomanipulationduringthecastrationprocedure.AdecreaseinBPdidnotnecessarilyrepresentadecreaseinHRinthesamepiglet.Similarobser-vationsweremadeinpiglets,lambsandcalvesunderhalothaneanesthesiaundergoingzoo-technicalprocedures[8,25,29].VanLieshoutetal.[30]attributedthisparadoxicaleffecttoavasovagalresponsetonoxiousstimuli.Theoccurrenceofbradycardiaandhypotensionduringseverepaincausedbythestretchingofabdominalorperinealviscerahasbeendescribedintheliterature[31].Asimilartypeofpaincouldbeinducedthroughthestretchingofthespermaticcord,andthereforetheperitoneum,inthecastrationprocess.Aboveacertainconcentration,halothaneinducesadepressorhemodynamicresponsetonoxiousstimuliinrats;however,thiseffecthasnotbeendescribedinanimalsunderisofluraneanesthesia[32].Otherexplanationscouldbealterationsinrespiratoryfunctionorincreasesinperipheralvascularresistance[29,33].AsthedecreasesinBPandHRweredirectlyrelatedtoastimulus,webelievethatitisreasonabletovaluebothalargeincreaseandalargedecreaseasasignofnociception.Allfourlocalanestheticsprovidedareductioninlimbmovementsduringskinincisionandcuttingofthespermaticcord.TheNaClgroupshowedthemostlimbmovementsduringcas-tration,andpigletsintheHgroupdidnotmoveatanytimepoint.Severalotherstudiesobservedabeneficialeffectregardinglimbmovementsinpigletscastratedunderlocalanesthe-sia[2,9,16].Itmustbenotedthatallthesestudieswerecarriedoutinconsciouspiglets.Apointofcriticismcouldbethatlimbmovementsarehardtoevaluateunderisofluraneanesthe-sia.Volatileanestheticsatcertainconcentrationsareknowntoblockmovementsinresponsetonoxiousstimuli[34].Toensurethatareactiontonoxiousstimuliwasstillpossible,theiso-fluraneconcentrationwasindividuallytitratedviareactiontoatoepinch.Toepinchwascho-senbecauseEgeretal.[35]foundthattoeclampingisapainfulstimulusandpromptsthebestreflextodetermineanestheticdepthinpiglets[36].Asthetoepinchwascarriedoutbyahuman,thepressureappliedmightbeinconsistent.Tominimizethisvarianceinappliedpres-sureandlocalization,thereflexwasalwaystestedbythesametwopersons,andthesameclampwasused.Onlywhenareactiontoatoepinchwasobservedwastheexperimentcontin-ued.Itcannotbefullyexcludedthatinsomeanimals,anesthesiamighthaveblockedsomereactions;intheNaClgroup,onlysixoutofninepigletsexhibitedlimbmovements.Neverthe-less,thelimbmovementsareinlinewiththeBPandHRresults,whichsuggeststhismodelproducedreliableresults.Regardingtheinjectiontechniqueusedinthisstudy,itmustbenotedthatpigletsinallexperimentalgroupsreceivingi.t.andsubscrotalinjectionsshowedclearlimbmovementresponses.Additionally,twoanimalsintheNaClgroupreactedtotheinjection.BPandHRininjectedpigletswerehigherthanthoseinthehandlinggroup,butnosignificantdifferencewasfound.Thesereactionsinresponsetoinjectionindicatethatinjectionsintothetestisarepainful.Anexplanationregardingwhypigletsinjectedwithalocalanestheticreactedmorecouldbethatlocalanestheticsareacidicsolutionsthatcouldprovokeaburningsensationintheinjectedarea.Thissuggeststhatinadditiontotheinjectionitself,thepHoftheappliedsolutionplaysaroleasapaintrigger.Hannaetal.[37]showedthatpaininducedbytheinjectionoflocalanestheticsiscausedbymultiplefactorsandcanbereducedbyaddingbicarbonate.Thismustbefurtherdiscussedifintratesticularinjectionistomeettherequire-mentsoftheGermanwelfareact,whichrequeststhetotaleliminationofpainduringthesur-gicalprocedure.Perhapsusinglowervolume,bufferedlocalanestheticsordifferentinjection
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ermanwelfareact,whichrequeststhetotaleliminationofpainduringthesur-gicalprocedure.Perhapsusinglowervolume,bufferedlocalanestheticsordifferentinjection Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,202012/17
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techniquescouldfurtherimproveinjectionpain.Hoganetal.[38]suggestswarmingthelocalanesthetictoreduceinjectionpain.Theoptimizationoftheinjectiontechniqueandtheverificationofwhetherthesameanalgesiceffectscanbeachievedbythesemethodsarepartoffurtherstudies.Regardingtheanalysisofstresshormonesaftercastrationaftertheadministrationoflocalanesthesia,theresultsofpreviousstudiesareinconclusive.Sutherlandetal.[39]didnotfindareducedcortisolresponseaftercastrationwiththeadministrationoflocalanestheticscom-paredtopigletscastratedwithoutanesthesia.Incontrast,intwootherstudies,theserumcorti-sollevelsofpigletstreatedwithlocalanestheticswereevenhigherthanthoseinthecontrolgroups[40,41].Rauhetal.[9]evenobservedanincreaseinepinephrineandnorepinephrineinpigletsinjectedwith2%procaine,andHofmannetal.[42]observedsimilareffectsofpro-caineoncortisolconcentrationsand1%lidocaineonchromograninAlevels.However,duetotheuseofdifferentlocalanesthetics,concentrations,applicationtimesandtypesofapplicationinthestudies,adirectcomparisonisnotpossible.Inthepresentstudy,thesefindingscouldnotbeconfirmed.Injectionintothetestisandcastrationdidnotcausesignificantchangesinthestresshormoneconcentrationsofcortisol,CgA,epinephrineornorepinephrineintheexperimentalgroups.Inthehandlinggroup,evenhigherincreasesthanthoseintheNaClgroupwererecorded.Anexplanationforthefailureofbloodhormonestoillustratethenociceptionexperiencedbythepigletsinourmodelmaybethattheprocedureswereperformedunderisofluraneanes-thesia.Thebaselinebloodsamplesweretaken31minutesaftertheinductionofanesthesia(31.04±7.1minutes).Weassumethatthehighbaselinecortisollevel,comparedtootherstud-ies[41,43,44],couldbecausedbybasicstressduetofactorssuchashandlingorinductionofanesthesiathroughamask.However,thelowcatecholaminebaselinecouldbeexplainedbytheabsenceofacutestresscausedbyhandling.Thebaselinewascomparabletostudiesinwhichbloodsamplesweretakenwithoutstressviaavenousportfrompigletswithoutanesthesia[45]orwithoutavenousportbutunderisofluraneanesthesia[44].Furthermore,inhumans,increasesincatecholamineandcortisolconcentrationsunderiso-fluraneanesthesiahavebeendescribed,andthesereactionscouldalsoappearinpiglets[46].However,significantincreasesincortisolconcentrationswithingroupswereobserved,sug-gestingageneral,group-independentincreaseinstressunderthismodel.Whereasdifferentconcentrationsandapplicationtechniquesoflidocaine[2,3,8,9,15–19,21,39,41,47–56]andprocaine[9,17,41,42,57–59]havebeenexcessivelystudiedinthecon-textofpigletcastration,bupivacainewasanalyzedonlyincombinationwithlidocainebyBonastreetal.[60].Tothebestofourknowledge,mepivacaine,anapproveddruginseveralEuropeancountriesforintraarticularandepiduralinjectionsinhorses,hasneverbeenusedinstudiesexaminingpigletcastration.Althoughallofthelocalanestheticsusedinourstudywereadministeredinhighdoses,nocardiovascularorpulmonarysideeffectswereobserved.Tospeeduptheonsetofactionandtoprolongthedurationofaction,epinephrineisoftenaddedtolocalanesthetics.Asapilotstudyshowedthati.t.incombinationwithsubscrotallyinjectedepinephrinedistortedthemeasurementsofthehemodynamicparameters(FigIinS1Appen-dix)andplasmaepinephrine(FigIIinS1Appendix),noepinephrinewasaddedtotheana-lyzedsubstances.Nosignificantdifferenceswerefoundbetweenthefourlocalanesthetics,indicatingthatallofthemobtainedsufficientanalgesiceffectsunderlightisofluraneanesthe-sia,reducingacutenociceptivecastrationpain.Alimitationofthepresentstudyisthatnociceptionisonlyassessedonthebasisofacutecar-diovascularandhumoralresponsesandlimbmovements.Toobtainamorecompletepictureofnociception,neuralnociceptiveprocessingmustbeincludedintheevaluationbystudying
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scularandhumoralresponsesandlimbmovements.Toobtainamorecompletepictureofnociception,neuralnociceptiveprocessingmustbeincludedintheevaluationbystudying Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,202013/17
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FosproteinexpressioninthespinalcordandEEGresponses.Thesedatawerealsocollectedandwillbepublishedseparatelyduetotheirhighcomplexity(manuscriptinpreparation).Furthercomparisonsbetweenthetestedsubstancesareplannedinawakepigletsconsider-ingbehaviorandpostcastrationpain,wherecharacteristicssuchasdurationofactionandtimeofonsetplayamoreimportantrole.Alltheseresultsmustbetakenintoaccountbeforeafinalevaluationoflocalanesthesiaasamethodtoeliminatepainduringpigletcastrationispossible. Conclusions Ourstudydemonstratesthatthenociceptioninducedbyintratesticularandsubcutaneousinjectionandcastrationcanbereliablyquantifiedbymeasuringcardiovascularresponsesandlimbmovementsunderisofluraneanesthesia.Anintratesticularinjectionwithasubcutaneousdepotofalocalanestheticpriortocastrationreducesnociception-relatedcardiovascularresponsesandlimbmovementscomparedtocastrationwithoutalocalanesthetic.Ourfindingsconfirmtheanalgesiceffectoftheinvestigatedlocalanestheticscausedbyblockingnociceptionduringcastrationinourexperimentalsetupinpiglets.However,theinjectionoflocalanestheticscausedvisiblenociception,asshownbyincreasedlimbmovements.Itmustbementionedthatourstudyinvestigatedtheanalgesiceffectsoflocalanesthesiaduringcastrationinpigletsunderlightnarcosis,whichmeansthatnociceptionwasevaluatedwiththeexclusionofstressandfear.Ifconsciouspigletsarecastrated,thenthesefactorswillinfluencethepiglets’behaviorandperceptionofpain.Whetherthismethodisalsopracticableandeffectiveinconsciouspigletsandhowthedifferentlocalanestheticsinfluencewoundheal-ingandpost-castrationbehaviorwillbeelucidatedinfurtherstudies. Supportinginformation S1Appendix.Systemicinfluenceofintratesticularlyandsubscrotallyinjectedepinephrine.(DOCX) AuthorContributions
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edinfurtherstudies. Supportinginformation S1Appendix.Systemicinfluenceofintratesticularlyandsubscrotallyinjectedepinephrine.(DOCX) AuthorContributions Conceptualization:SusanneZo¨ls,ChristineBaumgartner.Datacuration:AnnaM.Saller,JuliaWerner.Formalanalysis:YuryZablotski.Fundingacquisition:SusanneZo¨ls,ChristineBaumgartner.Investigation:AnnaM.Saller,JuliaWerner,JudithReiser,SteffanieSenf,PaulineDeffner,NoraAbendscho¨n,JohannesFischer,ChristineBaumgartner.Methodology:AnnaM.Saller,JuliaWerner,JudithReiser,SteffanieSenf,PaulineDeffner,NoraAbendscho¨n,ChristineWeiß,JohannesFischer,SusanneZo¨ls,ChristineBaumgartner.Projectadministration:SusanneZo¨ls,ChristineBaumgartner.Resources:MathiasRitzmann,SusanneZo¨ls,ChristineBaumgartner.Supervision:MichaelH.Erhard,MathiasRitzmann,SusanneZo¨ls,ChristineBaumgartner.Validation:ChristineBaumgartner.Visualization:AnnaM.Saller,JuliaWerner. Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,202014/17
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Writing–originaldraft:AnnaM.Saller,JuliaWerner.Writing–review&editing:JudithReiser,SteffanieSenf,PaulineDeffner,NoraAbendscho¨n,JohannesFischer,AndreaScho¨rwerth,ReginaMiller,ShanaBergmann,MichaelH.Erhard,MathiasRitzmann,SusanneZo¨ls,ChristineBaumgartner. References
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Abendscho¨n,JohannesFischer,AndreaScho¨rwerth,ReginaMiller,ShanaBergmann,MichaelH.Erhard,MathiasRitzmann,SusanneZo¨ls,ChristineBaumgartner. References 1.EuropeanFoodSafetyAuthority(EFSA).Opinionofthescientificpanelonanimalhealthandwelfare(AHAW)onarequestfromthecommissionrelatedtowelfareaspectsofthecastrationofpiglets.EFSAJ.2004;2:91.2.HornT,MarxG,vonBorellE.Behaviorofpigletsduringcastrationwithandwithoutlocalanesthesia.DtschTierarztlWochenschr.1999;106:271–274.PMID:104813693.McGloneJJ,HellmanJM.Localandgeneralanestheticeffectsonbehaviorandperformanceoftwo-andseven-week-oldcastratedanduncastratedpiglets.JAnimSci.1988;66:3049–3058.https://doi.org/10.2527/jas1988.66123049xPMID:32300674.IASPTaskForceonTaxonomy,editedbyH.MerskeyandN.Bogduk.PARTIII:PainTerms,ACurrentListwithDefinitionsandNotesonUsage.ClassificationofChronicPain.©1994;209–214,updated2011.5.TierschutzgesetzinderFassungderBekanntmachungvom18.Mai2006(BGBl.IS.1206,1313),daszuletztdurchArtikel101desGesetzesvom20.November2019(BGBl.IS.1626)gea¨ndertwordenist.6.IsonSH,CluttonRE,DiGiminianiP,RutherfordKM.Areviewofpainassessmentinpigs.FrontVetSci.2016;3:108.https://doi.org/10.3389/fvets.2016.00108PMID:279659687.HerskinMS.Paininpigs:characterisation,mechanismsandindicators.In:SˇpinkaM,editor.Advancesinpigwelfare.Duxford,UnitedKingdom:WoodheadPublishing;2018.p.506.8.HagaHA,RanheimB.Castrationofpiglets:theanalgesiceffectsofintratesticularandintrafunicularlidocaineinjection.VetAnaesthAnalg.2005;32:1–9.https://doi.org/10.1111/j.1467-2995.2004.00225.xPMID:156637339.RauhA,HofmannK,HarliziusJ,WeissC,NumbergerJ,ScholzT,etal.Painanddistressresponseofsucklingpigletstoinjectionandcastrationunderlocalanaesthesiawithprocaineandlicocaine—part2:defencebehaviour,catecholamines,coordinationofmovements.TierarztlPraxAusgGGrosstiereNutztiere.2019;47:160–170.10.HagaHA,TevikA,MoerchH.Electroencephalographicandcardiovascularindicatorsofnociceptionduringisofluraneanaesthesiainpigs.VetAnaesthAnalg.2001;28:126–131.https://doi.org/10.1046/j.1467-2987.2001.00051.xPMID:2840444211.HuangY,LiuZ,LiuW,YinC,CiL,ZhaoR,etal.Shortcommunication:salivaryhaptoglobinandchro-mograninAasnon-invasivemarkersduringrestraintstressinpigs.ResVetSci.2017;114:27–30.https://doi.org/10.1016/j.rvsc.2017.02.023PMID:2828404812.CasalN,MantecaX,EscribanoD,CeronJJ,FabregaE.Effectofenvironmentalenrichmentandherbalcompoundsupplementationonphysiologicalstressindicators(chromograninA,cortisolandtumournecrosisfactor-alpha)ingrowingpigs.Animal.2017;11:1228–1236.https://doi.org/10.1017/S1751731116002561PMID:2792726113.PrunierA,MounierAM,HayM.Effectsofcastration,toothresection,ortaildockingonplasmametabo-litesandstresshormonesinyoungpigs.JAnimSci.2005;83:216–222.https://doi.org/10.2527/2005.831216xPMID:1558306214.LirkP,HollmannMW,StrichartzG.Thescienceoflocalanesthesia:basicresearch,clinicalapplication,andfuturedirections.AnesthAnalg.2018;126:1381–1392.https://doi.org/10.1213/ANE.0000000000002665PMID:2918928015.Kluivers-PoodtM,HouxBB,RobbenSR,KoopG,LambooijE,HellebrekersLJ.Effectsofalocalanaes-theticandNSAIDincastrationofpiglets,ontheacutepainresponses,growthandmortality.Animal.2012;6:1469–1475.https://doi.org/10.1017/S1751731112000547PMID:2303152016.HanssonM,LundeheimN,NymanG,JohanssonG.Effectoflocalanaesthesiaand/oranalgesiaonpainresponsesinducedbypigletcastration.ActaVetScand.2011;53:34.https://doi.org/10.1186/1751-0147-53-34PMID:2162779717.RittershausD.Topischeana¨sthesieverfahrenzurschmerzreduktionbeidersaugferkelkastration.Inau-guralDissertation,UniversityofVeterinaryMedicineHannover,Foundation.2009.18.CourboulayV,HemonicA,GadonnaM,PrunierA.Castrationunderanalgesiaorlocalanesthesia:impactonpainandlabourdemand.In:AnnualmeetingoftheEuropeanAssociationforanimalproduc-tion.Saint-Gilles,France;2010.p.138.
chunk 34 · 70 tokens
deranalgesiaorlocalanesthesia:impactonpainandlabourdemand.In:AnnualmeetingoftheEuropeanAssociationforanimalproduc-tion.Saint-Gilles,France;2010.p.138. Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,202015/17
chunk 35 · 1045 tokens
19.Marsˇa´lekP,SvobodaM,BernardyJ,VečerekV.Concentrationsofneopterin,biopterin,andcortisolassociatedwithsurgicalcastrationofpigletswithlidocaine.CzechJAnimSci.2015;60:473–478.20.Berchtold,S.OptimierungderInjektionsana¨sthesiefu¨rdieFerkelkastration.InauguralDissertation,Uni-versita¨tZu¨rich.2015.21.HugPJ,CapVH,HoneggerJ,Schupbach-RegulaG,SchwarzA,Bettschart-WolfensbergerR.Optimi-zationofanalgesiaforpigletcastrationunderisofluraneanaesthesiawithparenteralbutorphanol,meloxicamorintratesticularlidocaine.SchweizArchTierheilkd.2018;160:461–467.https://doi.org/10.17236/sat00169PMID:2998955322.RDevelopmentCoreTeam.Alanguageandenvironmentforstatisticalcomputing.Vienna,RFounda-tionforStatisticalComputing;2017.23.TaylorAA,WearyDM,LessardM,BraithwaiteL.Behaviouralresponsesofpigletstocastration:theeffectofpigletage.ApplAnimBehavSci.2001;73:35–43.https://doi.org/10.1016/s0168-1591(01)00123-xPMID:1135628924.vonBorellE,BaumgartnerJ,GiersingM,JagginN,PrunierA,TuyttensFA,etal.Animalwelfareimpli-cationsofsurgicalcastrationanditsalternativesinpigs.Animal.2009;3:1488–1496.https://doi.org/10.1017/S1751731109004728PMID:2244498225.ZbindenAM,Petersen-FelixS,ThomsonDA.Anestheticdepthdefinedusingmultiplenoxiousstimuliduringisoflurane/oxygenanesthesia.II.Hemodynamicresponses.Anesthesiology.1994;80:261–267.26.AntogniniJF,BergK.Cardiovascularresponsestonoxiousstimuliduringisofluraneanesthesiaareminimallyaffectedbyanestheticactioninthebrain.AnesthAnalg.1995;81:843–848.https://doi.org/10.1097/00000539-199510000-00032PMID:757402127.BovaJF,daCunhaAF,StoutRW,BhumiratanaS,AlfiDM,EisigSB,etal.BupivacainemandibularnerveblockaffectsintraoperativebloodpressureandheartrateinaYucatanminiatureswinemandibu-larcondylectomymodel:apilotstudy.JInvestSurg.2015;28:32–39.https://doi.org/10.3109/08941939.2014.971207PMID:2539429528.TaylorAA,WearyDM.Vocalresponsesofpigletstocastration:identifyingproceduralsourcesofpain.ApplAnimBehavSci.2000;70:17–26.https://doi.org/10.1016/s0168-1591(00)00143-xPMID:1098642029.JohnsonCB,SylvesterSP,StaffordKJ,MitchinsonSL,WardRN,MellorDJ.Effectsofageontheelectroencephalographicresponsetocastrationinlambsanaesthetizedwithhalothaneinoxygenfrombirthto6weeksold.VetAnaesthAnalg.2009;36:273–279.https://doi.org/10.1111/j.1467-2995.2009.00448.xPMID:1939777930.VanLieshoutJJ,WielingW,KaremakerJM,EckbergDL.Thevasovagalresponse.ClinSci(Lond).1991;81:575–586.31.PriebeHJ,SkarvanK.RegulationofthecardiovascularsystemIn:NijhawanN,WarltierDC,editors.Cardiovascularphysiology.London:BMJPublishingGroup;2000.pp.213–239.32.GibbsNM,LarachDR,SkeehanTM,SchulerHG.Halothaneinducesdepressorresponsestonoxiousstimuliintherat.Anesthesiology.1989;70:503–510.33.TaylorPM,KirbyJJ,ShrimptonDJ,JohnsonCB.Cardiovasculareffectsofsurgicalcastrationduringanaesthesiamaintainedwithhalothaneorinfusionofdetomidine,ketamineandguaifenesininponies.EquineVetJ.1998;30:304–309.https://doi.org/10.1111/j.2042-3306.1998.tb04102.xPMID:970511334.EgerEI,RainesDE,ShaferSL,HemmingsHCJr.,SonnerJM.Isanewparadigmneededtoexplainhowinhaledanestheticsproduceimmobility?AnesthAnalg.2008;107:832–848.https://doi.org/10.1213/ane.0b013e318182aedbPMID:1871389235.EgerEI,JohnsonBH,WeiskopfRB,HolmesMA,YasudaN,TargA,etal.Minimumalveolarconcentra-tionofI-653andisofluraneinpigs:definitionofasupramaximalstimulus.AnesthAnalg.1988;67:1174–1176.PMID:319573436.SatasS,HaalandK,ThoresenM,SteenPA.MACforhalothaneandisofluraneduringnormothermiaandhypothermiainthenewbornpiglet.ActaAnaesthesiolScand.1996;40:452–456.https://doi.org/10.1111/j.1399-6576.1996.tb04468.xPMID:873869037.HannaMN,ElhassanA,VelosoPM,LesleyM,LissauerJ,RichmanJM,etal.Efficacyofbicarbonateindecreasingpainonintradermalinjectionoflocalanesthetics:ameta-analysis.RegAnesthPainMed.2009;34:122–125.https://doi.org/10.1097/AAP.0b013e31819a12a6PMID:1928271138.HoganME,vanderVaartS,PerampaladasK,MachadoM,EinarsonTR,TaddioA.Systematicreviewandmeta-analysisoftheeffectofwarminglocalanestheticsoninjectionpain.AnnEmergMed.2011;58:86–98e81.https://doi.org/10.1016/j.annemergmed.2010.12.001PMID:2131681239.SutherlandMA,BackusBL,BrooksTA,McGloneJJ.Theeffectofneedle-freeadministrationoflocalanestheticonthebehaviorandphysiologyofcastratedpigs.JVetBehav.2017;21:71–76.
chunk 36 · 70 tokens
MA,BackusBL,BrooksTA,McGloneJJ.Theeffectofneedle-freeadministrationoflocalanestheticonthebehaviorandphysiologyofcastratedpigs.JVetBehav.2017;21:71–76. Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,202016/17
chunk 37 · 1070 tokens
40.BarticciottoLS,LunaSPL,LorenaSERDS,TellesFG,BertoDA.Weightgain,behavioralandcortisolchangesafterorchiectomywithorwithoutlocalanaesthesiainpiglets.SeminCiencAgrar.2016;37:1307–1315.41.ZanklA,RitzmannM,ZolsS,HeinritziK.Theefficacyoflocalanaestheticsadministeredpriortocastra-tionofmalesucklingpiglets.DtschTierarztlWochenschr.2007;114:418–422.PMID:1807793242.HofmannK,RauhA,HarliziusJ,WeissC,ScholzT,Schulze-HorselT,etal.Painanddistressresponsesofsucklingpigletstoinjectionandcastrationunderlocalanaesthesiawithprocaineandlido-caine—part1:cortisol,chromograninA,woundhealing,weights,losses.TierarztlPraxAusgGGros-stiereNutztiere.2019;47:87–96.43.ZolsS,RitzmannM,HeinritziK.EinflussvonSchmerzmittelnbeiderKastrationma¨nnlicherFerkel.BerlMunchTierarztlWochenschr.2006;119:193–196.44.SchulzC,RitzmannM,PalzerA,HeinritziK,Zo¨lsS.AuswirkungeneinerIsofluran-InhalationsnarkoseaufdenpostoperativenKastrationsschmerzvonFerkeln.BerlMu¨nchTiera¨rztlWschr.2007;120:177–182.45.MayfieldSR,StonestreetBS,ShaulPW,BrubakkAM,SusaJ,OhW.Plasmacatecholamineconcen-trationsofnewbornpigletsinthermoneutralandcoldenvironments.JDevPhysiol.1989;11:331–334.PMID:259275046.NishiyamaT,YamashitaK,YokoyamaT.Stresshormonechangesingeneralanesthesiaoflongdura-tion:isoflurane-nitrousoxidevssevoflurane-nitrousoxideanesthesia.JClinAnesth.2005;17:586–591.https://doi.org/10.1016/j.jclinane.2005.03.009PMID:1642752747.WhiteRG,DeShazerJA,TresslerCJ,BorcherGM,DaveyS,WaningeA,etal.Vocalizationandphysio-logicalresponseofpigsduringcastrationwithorwithoutalocalanesthetic.JAnimSci.1995;73:381–386.https://doi.org/10.2527/1995.732381xPMID:760176848.GutzwillerA.Kastrationvonferkelnunterlokalana¨sthesie.Agrarforschung.2003;10:10–13.49.RanheimB,HagaHA,IngebrigtsenK.Distributionofradioactivelidocaineinjectedintothetestesinpig-lets.JVetPharmacolTher.2005;28:481–483.https://doi.org/10.1111/j.1365-2885.2005.00675.xPMID:1620731250.Kluivers-PoodtM,ZonderlandJJ,VerbraakJ,LambooijE,HellebrekersLJ.Painbehaviouraftercastra-tionofpiglets;effectofpainreliefwithlidocaineand/ormeloxicam.Animal.2013;7:1158–1162.https://doi.org/10.1017/S1751731113000086PMID:2338811651.Perez-PedrazaE,Mota-RojasD,Ramirez-NecoecheaR,Guerrero-LegarretaI,Martinez-BurnesJ,Lezama-GarciaK,etal.Effectofthenumberofincisionsanduseoflocalanesthesiaonthephysiologi-calindicatorsofsurgically-castratedpiglets.IntJVetSciMed.2018;6:159–164.https://doi.org/10.1016/j.ijvsm.2018.10.002PMID:3056459052.TellesFG,LunaSPL,TeixeiraG,BertoDA.Long-termweightgainandeconomicimpactinpigscas-tratedunderlocalanaesthesia.VetAnimSci.2016;1–2:36–39.53.HancockTM,CaulkettNA,PajorEA,GrenwichL.Aninvestigationoftheeffectsofintratesticularalfaxa-loneandlidocaineduringcastrationinpiglets.VetAnaesthAnalg.2018;45:858–864.https://doi.org/10.1016/j.vaa.2018.07.002PMID:3025399954.RigamontiS,Bettschart-WolfensbergerR,SchwarzA,NussbaumerI.ErmittlungeinesfeldtauglichenInjektionsana¨sthesieprotokollszurKastrationvon8bis14-ta¨gigenFerkeln.SchweizerArchivfu¨rTier-heilkunde.2018;160:469–474.55.LomaxS,HarrisC,WindsorPA,WhitePJ.HerabsetzungdesSchmerzempfindensanderKastrations-wundebeineugeborenenFerkelndurcheinetopischangewandteLokalana¨sthesie.TierarztlUmsch.2018;73.56.YunJ,OllilaA,ValrosA,Larenza-MenziesP,HeinonenM,OlivieroC,etal.Behaviouralalterationsinpigletsaftersurgicalcastration:effectsofanalgesiaandanaesthesia.ResVetSci.2019;125:36–42.https://doi.org/10.1016/j.rvsc.2019.05.009PMID:3112582057.Zo¨lsS.Mo¨glichkeitenderSchmerzreduzierungbeiderKastrationma¨nnlicherSaugferkel.InauguralDissertation,Ludwig-Maximilians-Universita¨t.2006.58.LeidigMS,HertrampfB,FailingK,SchumannA,ReinerG.Painanddiscomfortinmalepigletsduringsurgicalcastrationwithandwithoutlocalanaesthesiaasdeterminedbyvocalisationanddefencebehaviour.ApplAnimBehavSci.2009;116:174–178.59.TavellaG,ScolloA,MazzoniC,ContieroB,GottardoF.Useoflocalanaesthesiaduringpigletcastra-tion:painevaluation.In:AttidellaSocietàItalianadiPatologiaedAllevamentodeiSuini,XLIIMeetingAnnuale;Montichiari,Italia:SocietàItalianadiPatologiaedAllevamentodeiSuini;2016.pp.69–76.60.BonastreC,MitjanaO,TejedorMT,CalaviaM,YusteAG,UbedaJL,etal.Acutephysiologicalresponsestocastration-relatedpaininpiglets:theeffectoftwolocalanestheticswithorwithoutmeloxi-cam.Animal.2016;10:1474–1481.https://doi.org/10.1017/S1751731116000586PMID:27080170
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tedpaininpiglets:theeffectoftwolocalanestheticswithorwithoutmeloxi-cam.Animal.2016;10:1474–1481.https://doi.org/10.1017/S1751731116000586PMID:27080170 Analgesiceffectsoflocalanesthesiainpigletsundergoingcastration PLOSONE|https://doi.org/10.1371/journal.pone.0236742July30,202017/17