Cuttance et al. - 2019 - Effects of a topically applied anaesthetic on the

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Full Terms & Conditions of access and use can be found athttps://www.tandfonline.com/action/journalInformation?journalCode=tnzv20 New Zealand Veterinary Journal ISSN: 0048-0169 (Print) 1176-0710 (Online) Journal homepage: https://www.tandfonline.com/loi/tnzv20 Effects of a topically applied anaesthetic on thebehaviour, pain sensitivity and weight gain ofdairy calves following thermocautery disbuddingwith a local anaestheticEL Cuttance, WA Mason, DA Yang, RA Laven, J McDermott & K InglisTo cite this article: EL Cuttance, WA Mason, DA Yang, RA Laven, J McDermott & K Inglis (2019)Effects of a topically applied anaesthetic on the behaviour, pain sensitivity and weight gain ofdairy calves following thermocautery disbudding with a local anaesthetic, New Zealand VeterinaryJournal, 67:6, 295-305, DOI: 10.1080/00480169.2019.1640651 To link to this article: https://doi.org/10.1080/00480169.2019.1640651 © 2019 The Author(s). Published by InformaUK Limited, trading as Taylor & FrancisGroup View supplementary material Accepted author version posted online: 04Jul 2019.Published online: 07 Aug 2019. Submit your article to this journal Article views: 396 View related articles View Crossmark data

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SCIENTIFICARTICLE E ectsofatopicallyappliedanaestheticonthebehaviour,painsensitivityandweightgainofdairycalvesfollowingthermocauterydisbuddingwithalocalanaestheticELCuttance a,WAMasona,DAYang b,RALaven b,JMcDermottaandKIngliscaVetEntResearch,TeAwamutu,NewZealand;bSchoolofVeterinaryScience,MasseyUniversity,Palmerston,NewZealand;cBayerNewZealandLtd,Auckland,NewZealandABSTRACTAims:Tocomparethee ectofatopicallyappliedanaesthetictonopainrelieformeloxicamonthebehaviouralresponses,painsensitivityandweightgainofcalvesfollowingdisbuddingwithorwithoutsedation.Methods:Atotalof364,2–6week-oldcalvesfromthreecommercialfarmsweresystematicallyallocatedtooneofsixtreatmentgroups.Allcalvesreceivedacornualnerveblockpriortodisbudding,withhalfrestrainedinacrateandhalfsedatedwithxylazine.Withinthesegroupsonethirdreceivednofurthertreatment(control),onethirdweretreatedwithmeloxicam>10minutespriortodisbuddingandonethirdreceivedatopicalanaestheticappliedtothehornbudwoundsfollowingdisbudding.Thefrequencyofear icks,headshakes,headscratchesandpainsensitivityofthewoundwererecordedonuptoeightoccasionsover24hoursafterdisbudding.Calveswereweighedbefore,and7and28daysafter,disbuddingtodetermineaveragedailyweightgain(ADG).Results:Comparedtocalvesinthecrate-controlgroup,allothergroupshadreducedear icksatalltimesfollowingdisbudding(p<0.01).Treatmentwithmeloxicamandtopicalanaesthesia inadditiontosedationreducedheadscratchescomparedtocalvesinthecrate-controlgroup (p≤0.013).At22hoursafterdisbuddingheadshakeswerereducedinsedatedcalvestreatedwithtopicalanaestheticcomparedtocalvesinthecrate-controlgroup(p<0.001).Pain sensitivitywaslowerinallsedatedcalvesthanunsedatedcalves(p<0.001).TheADG

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edwithtopicalanaestheticcomparedtocalvesinthecrate-controlgroup(p<0.001).Pain sensitivitywaslowerinallsedatedcalvesthanunsedatedcalves(p<0.001).TheADG betweenDays0–7was0.14(95%CI=0.015–0.274)kg/daygreaterinsedatedcalvestreatedwithmeloxicamthancalvesinthecrate-controlgroup(p=0.03),andtheADGbetweenDays 0–28tendedtobe0.06(95%CI=−0.01–0.13)kg/daygreaterinsedatedcalvestreatedwithtopicalanaestheticthancalvesinthecrate-controlgroup(p=0.09). Conclusionandclinicalrelevance:Sedationofcalvesfordisbuddingreducedthepainexperiencedinthefollowing24hours.Therewasabene ttoprovidingcalveswithtopicalanaestheticfollowingdisbuddingonbehaviouralresponsesandpainsensitivity,whichwas similartothatoftreatingcalveswithmeloxicam.Abbreviations:ADG:Averagedailygain;IRR:Incidencerateratio;NSAID:Non-steroidalanti-in ammatorydrugARTICLEHISTORYReceived16October2018Accepted6June2019Publishedonline4July2019KEYWORDSDisbudding;dehorning;topicalanaesthetic;painrelief;calves;behaviour;weightgainIntroductionInNewZealandlargenumbersofcalvesaredisbuddedeveryyear,usuallywithinthe rst2monthsoflife.Whilecurrently,disbuddingispermittedwithoutlocalanaesthesia,newregulationsduetobeintroducedon1October2019requirethatthedisbuddingofall calvesinNewZealandmustbeundertakenusinganappropriatelyplacedande ectivelocalanaesthetic(Anonymous2018).However,whiledisbuddingwithlocalanaesthesiaise ectiveforreducingphysiologicalandbehaviouralresponsesduringdisbudding(Petrieetal.1996),oncethelocalanaesthesiawearso (within2–3hours),behaviourssuchasear ickingandheadshakingincrease,asdoconcentrationsofcor- tisol,withthesepain-associatedchangeslastingforat

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siawearso (within2–3hours),behaviourssuchasear ickingandheadshakingincrease,asdoconcentrationsofcor- tisol,withthesepain-associatedchangeslastingforat least24hoursafterdisbudding(FaulknerandWeary2000;Sutherlandetal.2002).Thepainassociatedwithdisbuddingcanbereducedbygivingasystemicnon-steroidalanti-in am-matorydrug(NSAID;Sta ordetal.2003;Heinrichetal.2010;Batesetal.2015)andsedation(McMeekanetal.1999;Batesetal.2016),althoughneitherofthesearee ectiveateliminatingthephysiologicalandbehav-iouralresponsesduringdisbudding.Furthermore,©2019TheAuthor(s).PublishedbyInformaUKLimited,tradingasTaylor&FrancisGroupThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommonsAttribution-NonCommercial-NoDerivativesLicense(http://creativecommons.org/licenses/by-nc-nd/4.0/),whichpermitsnon-commercialre-use,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited,andisnotaltered,transformed,orbuiltuponinanyway. CONTACTE.L.Cuttance emma.cuttance@vetent.co.nz Supplementaldataforthisarticlecanbeaccessedathttps://doi.org/10.1080/00480169.2019.1640651. NEWZEALANDVETERINARYJOURNAL2019,VOL.67,NO.6,295–305https://doi.org/10.1080/00480169.2019.1640651

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whilstmanycalvesinNewZealandaredisbuddedundersedation(N.Harding1pers.comm.),theuseofanalgesicsincalvesdisbudded,eitherundersedationorwhilstunsedatedandrestrainedinacrate,islimitedduetotheadditionalcostandperceivedlackofeconomicbene t.Thewelfareofdairycalvesiscomingundergreaterscrutinyasconsumersincreasinglyconsideranimalwelfarewhenpurchasingfood(Verbeke2009).There-forethereisaneedtoreducetheimpactofdisbuddingoncalfwelfarebeyondtheuseofjustlocalanaesthesia,andforapracticalandcoste ectivewayofdeliveringadditionalpainreliefduringandafterdisbudding.Theonlyregisteredtopicalanaestheticdrugforlargeanimaluseisanantisepticgelspraycontainingligno-caine,bupivacaineandadrenaline(Tri-Solfen;Bayer AustraliaLtd.),whichwasoriginallyregisteredinAus-traliaforuseinlambstoprovidepainrelieffollowingmulesingandtaildocking.Since2016Australianregis- trationhasincludedprovisionofpainreliefduringand followingsurgicalcastrationoflambsandcalves,andfromJune2018ithasbeenregisteredforuseaftercalfdisbuddingordehorning.Thisproductwasevaluatedin30Holstein-Friesian,2montholdcalves,whenappliedafterscoopdehorning, comparedtonopainrelief,andwasfoundtoreduceor removeresponsestomechanicalstimulationfrom4–24hoursafterapplication(Espinozaetal.2013).Inanotherstudythetopicalanaesthetic,appliedafter scoopdehorning,wascomparedwithacornualnerve blockappliedpriortodehorning,andfoundnodi er-enceinpainsensitivityafterdehorning(McCarthyetal.2016).Howeverthisstudyhaderrorsinitsstatisticalanalysisandwasgrosslyunderpoweredtodetectanydi erences.Anotherstudy,using6–8month-oldBosindicuscalvesundergoingconcurrentcastrationandamputationdehorning,investigatedtheuseofthe topicalanaestheticandbuccalmeloxicam,withoutanylocalanaesthesia,onpost-operativeweightgain

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entcastrationandamputationdehorning,investigatedtheuseofthe topicalanaestheticandbuccalmeloxicam,withoutanylocalanaesthesia,onpost-operativeweightgain andbehaviour.Verylittleconsistente ectoftreatmentwasfoundonmostofthemeasuredbehavioursor weightgainoverthe rst6daysaftercastrationanddehorning(VanderSaagetal.2018b).Inasimilarstudyusing6–8month-oldHerefordcalvesunder-goingamputationdehorningalone,therewasno cleare ectoftopicalanaestheticorbuccalmeloxicamonbehaviour,maximumwoundtemperatureorwoundmorphologyafterdehorning(VanderSaagetal.2018a).ThesestudieshavelimitedrelevanceoutsideAustraliaandsimilarextensiverangefarmingsystems, astheydidnotinvestigatetheuseoftopicalanaes-theticalongsidelocalanaesthesia.Topicalanaesthetics cannotbeusedtocontrolpainduringdisbudding,aswouldbelegallyrequiredinmanyjurisdictions,includ-ingNewZealandafter1October2019.Furthermore,allthestudiesusedamputationorscoopdehorningof2–8month-oldcalves,ratherthanhotirondisbuddingof 2–3week-oldcalveswhichismuchmorecommononNewZealanddairyfarms.Inadditionnostudieshaveevaluatedtheuseoftopicalanaestheticincalvessedatedwithxylazinepriortodisbudding,whichis thestandardpracticeforveterinarian-leddisbudding ondairyfarmsinNewZealand.Theaimsofthisstudyweretoinvestigatethee ectofatopicallyappliedlocalanaestheticfollowingdis- budding,usingeitheracrateforrestraintorsedation,incomparisontoeithertheNSAIDmeloxicamadminis-teredatdisbuddingornopost-disbuddingpainrelief, onthebehaviouralresponses,painsensitivityandweightgainofcalves.MaterialsandmethodsCalfselectionandallocationtogroupsAllanimalprocedureswereapprovedbytheRuakuraAnimalEthicsCommittee(AgResearch,Hamilton,NZ).Thisstudywasconductedbetween26Marchand4May2018onthreeconvenientlylocated,autumn-

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wereapprovedbytheRuakuraAnimalEthicsCommittee(AgResearch,Hamilton,NZ).Thisstudywasconductedbetween26Marchand4May2018onthreeconvenientlylocated,autumn- calving,commercialfarmsintheWaikatoregionoftheNorthIslandofNewZealand.Twoweekspriortothestudystartdate,anelec-troniclistoftheidenti cation,dateofbirthandbreedofallcalvesbornbetween1stFebruary2018upuntilthe14dayspriortothestudystartdate wereprovidedbythefarmer.Allcalvesbetween2–6weeksofageonthestudystartdate(Day0)wereeli-gibletobeexaminedforselectioninthetrial.AlleligiblecalveswereexaminedonDay−1forsignsofdisease(e.g.navelill,scours,pneumonia)by aveterinarianandcheckedforthepresenceofhornbuds.Calveswithdiseaseorpolledwerenoteligible forthetrial.Everyhealthy,eligiblecalfwasweighedonelectronicweighscales.OnFarms1and2,wherethereweresmallernumbersofcalves,theageofthe calvesrangedfrom2–6weekssocalveswereorderedbyweightandsystematicallyallocatedintooneofsix groups.OnFarm3therewere60calvespervisit, whichwere rstcategorisedaccordingtoageandthenwithinagecategorytheywereorderedbyweightandsystematicallyallocatedintooneofsixgroups.Themeanweightandageofthesixgroups weredeterminedtoensuretherewerenomajordiscre-panciesbetweengroups.AdescriptionofthetreatmentgroupsisshowninTable1.Asthereweremultipleoutcomesmeasuredforthetrial,calveswereallocatedbycohortforeitherbehaviouralobservationorpainsensitivitytesting (Figure1).The rstcohortofeligiblecalvesonafarmwereallallocatedforbehaviouralobservation.The 1N.Harding,DairyNZ,Hamiton,NewZealand.296 E.CUTTANCEETAL.

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secondcohortofcalvesthatweredisbuddedeitherdaysorweekslater,dependingonthefarmandageofthecalves,wereallallocatedtopainsensitivity testing.Thereweretwocohortsperfarmandbehav-iouralobservationsandpainsensitivitymeasurementswereseparatedbybetween2daysand3weeks.Calvesassignedtohavebehaviouralobservationsrecordedhadtheirnumberspraymarkedalongtheir sidesandtheirbacks,wereseparatedintotheirdesig- natedgroupsandwereplacedinsixseparatepenswithinthesamecalfhouseonDay−1.Calvesassignedtopainsensitivitytestingwereseparatedintotwo groups;oneforsedationandoneforcratedisbudding.ExperimentalprocedureAllcalveswerefedtheeveningbeforeDay0butnoton themorningofDay0.Twoteamsoftechnicianscarried outthedisbuddingfollowingadministrationoflocalanaestheticnerveblocks;oneteamoftwodisbuddedcalveswhiletheywerefullyconscious,restrainedina crateandtheotherteamoftwodisbuddedfollowingsedation.Thetwoteamsworkedsimultaneouslyonthegroupsofcalves.Thesamepersoninthegroup oftwoadministeredallthenerveblocksandthe otherteammemberdidallthedisbudding.Forcalvesthatweresedated,theywereinjectedwith3–4mg(0.15–0.2mL)/10kgof20mg/mLxylazine(Xylazine2%Injection;PhoenixPharmDistributors,Auckland,NZ)I/Mintheneck.Forthemajorityofcalves,thiswasadoseof0.8mL(16mg),butvaried from0.6–1.2mL(12–24mg),dependingontheweightofthecalf.Animalsweremarkedonceinjected toensurethesameanimalwasnotinjectedtwice.Inallcalvesbothhornsweredesensitisedusingacornualnerveblockatleast10minutespriortodisbud- ding,byinjecting5mL(100mg)of20mg/mLligno- caine(Bomacaine;BayerNewZealand,Auckland,NZ) atdepthofapproximately1cmunderthetemporalridgearoundeachcornualnerve.Calvesthatwereallocatedtoreceivemeloxicamwereinjectedwith50mg/100kg(1.4mL)of20mg/mLmelox- icam(Metacam20;BoehringerIngelheimNZLtd,Auck-land,NZ)S/Cintheneckfollowingthecornualnerve

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ivemeloxicamwereinjectedwith50mg/100kg(1.4mL)of20mg/mLmelox- icam(Metacam20;BoehringerIngelheimNZLtd,Auck-land,NZ)S/Cintheneckfollowingthecornualnerve blockandatleast10minutespriortodisbudding.Inallcalvesthehornbudwasprepared rstbyshavingthehairaroundthesiteusingelectricclippers. Disbuddingwasperformedbythermocauteryusinga gasheatedcleaninstrumentwitha18mmdiameterhead(ExpressLPGorFarmHanddisbudder,ShoofHamilton,NZ).Thehornbudwasremovedcompletely duringtheprocedure.Ifcalvesshowedanindicationofpainafterdisbuddingstarted,disbuddingwasstoppedandthecornualnerveblockwasrepeated.Followingdisbuddingthewoundateachhornbudwastreatedwitheither2mLoftopicalanaestheticsol- ution(Tri-Solfen(BayerNewZealandLtd),containing 40.6g/Llignocainehydrochloride,4.2g/Lbupivacainehydrochloride,24.8mg/Ladrenaline(asacidtartrate)and5.0g/Lcetrimide)or2mLofaplacebo.The placebowasidenticaltothetopicalanaestheticbutdid notincludeanylignocaine,bupivacaine,adrenalineorcetrimide.Thesolutionsweredeliveredusingahandheldapplicator(V-Grip6mLapplicator;GenesisIndustries,Mudgee,NSW,Australia).Insomecaseswhenitrano thewoundsiteexcesswascaughtwithatowelonthesideof theheadtoavoidproductgoingintotheeyesofcalves. Table1.Descriptionofthesixdi erenttreatmentgroupsusedtoinvestigatethee ectofatopicalanaesthetic(TA)aonthebehaviour,painsensitivityandweightgainofdairycalvesfollowingcauterydisbudding.GroupTreatment1Cratedisbudding,localanaestheticandTAplacebo5mLlignocainebappliedtoeachhornbud,4mLTAplaceboafterdisbudding2Cratedisbudding,localanaestheticandmeloxicam andTAplacebo5mLlignocainebappliedtoeachhornbud,1.4mLS/C meloxicamc,4mLTAplaceboafterdisbudding3Cratedisbudding,localanaestheticandTA5mLlignocainebappliedtoeachhornbud,4mLTAafter

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ppliedtoeachhornbud,1.4mLS/C meloxicamc,4mLTAplaceboafterdisbudding3Cratedisbudding,localanaestheticandTA5mLlignocainebappliedtoeachhornbud,4mLTAafter disbudding4Sedationdisbudding,localanaestheticandTAplacebo0.8mLI/Mxylazined,5mLlignocainebappliedtoeachhornbud,4mLTAplacebo afterdisbudding5Sedationdisbudding,localanaestheticandmeloxicamandTAplacebo0.8mLI/Mxylazined,5mLlignocainebappliedtoeachhornbud,1.4mLS/Cmeloxicamc,4mLTAplaceboafterdisbudding6Sedationdisbudding,localanaestheticandTA0.8mLI/Mxylazined,5mLlignocainebappliedtoeachhornbud,4mLTAafter disbuddingaTri-Solfen(BayerNewZealandLtd,Auckland,NZ).b20mg/mLlignocaine(Bomacaine,BayerNewZealand).c20mg/mLmeloxicam(Metacam20;BoehringerIngelheimNZLtd,Auck-land,NZ).d20mg/mLxylazine(Xylazine2%Injection;PhoenixPharmDistributors,Auckland,NZ). Figure1.Diagrammaticrepresentationshowingtheallocationwithinfarmsofcalvestobedisbuddedinacrateorsedated,andtoreceivenofurthertreatment(C),orreceiveatopical anaesthetic(TA)ormeloxicam(M).The rstcohortwasobservedafterdisbuddingforbehaviouralmeasurements, and3–21dayslaterthesecondcohorthadpainsensitivitymeasurementsrecordedafterdisbudding.NEWZEALANDVETERINARYJOURNAL 297

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Afterdisbudding,allcalvesthatwereallocatedtobehaviouralobservationsremainedintheirseparatepensuntil24hoursfollowingdisbudding.Allcalves thatwereallocatedtothepainsensitivitytestingwereintwojoinedpens(oneforsedatedcalvesandoneforcratecalves)for24hours.After24hoursallcalves werejoinedtogether.Theywereprovidedwithclean water,anewbatchofcalfmealandamilkfeed.Theremainderofthefeedingwasasperusualfarmpractice.BehaviouralobservationCalvesinthepenswerevideorecorded,startingat12:00hoursonDay−1andcontinuinguntil09:00hoursonDay1.FourArloPro2(ArloTechnologiesInc.,SanJose,CA,USA)videocameraswithnightvisionweremountedneartheroofofthecalfpens.Theywereposi- tionedsuchthatallsixtreatmentpenswereobservableinatleastoneofthecamerarecordings,andweretestedtoensurethattheywereabletocaptureallareas ofthecalfpens.Approximately7–10minutesofvideoweredown-loadedatthestartofeachofhour,at0,1,3,5,7,9, 12and22hoursfollowingdisbudding,ontoArloTech- nologiescloudsystem,whichwerethensubsequentlycopiedontoUSBdrivesforobservations.Thereforeforeachindividualcalfatotalof∼65–80minutesoffootagewasrecordedover24hours.Atotalof22trainedobserverswatchedthevideofootageforear icking,headshakingandheadscratch-ingbyindividualcalves,asdescribedinTable2.Theobserversweresupervisedbytwooftheauthors(ELC andWAM)andworkedinpairstowatchthefootage togetherona50cmcomputerscreen.Theobservers wereprovidedwithaselectionofspeci cvideosandwereinstructedonwhatpentheywereobserving, thecalfidenti cationnumbersinthatpenandthetimeperiodofobservation.Theyeachwatchedasinglecalfinthepen,thenanotheruntilallcalveswereobservedonceforthattime.Theywereencour- agedtore-watchthefootageandaskforhelpfromsupervisorsforcertainty.Theyrecordedthecalfnumber,thedescriptionofthecalf,andthecountof

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ttime.Theywereencour- agedtore-watchthefootageandaskforhelpfromsupervisorsforcertainty.Theyrecordedthecalfnumber,thedescriptionofthecalf,andthecountof thebehavioursshownthroughoutthetimeperiods.Afterapairhad nishedwatchingallthecalvesonce,anotherpairofobserversfollowedthesameprocedurewiththesamevideos.Therefore,eachcalfateachtime waswatchedbybetween2–4separatetrainedobser-verswhowereunawareofanypreviousobservation results.Thecalvesthatwerepositionedinthepens furthestawayfromthecameraswereobservedmorefrequently.Theobservershadnoknowledgeofthetrialotherthanthebehavioursthattheyhadto recordandwerethereforecompletelyblinded.Atthecompletionoftheobservations,thedatawerecollatedsoalltheobservationsofacalffromafarmata settimecouldbecomparedtodeterminediscrepancies betweenobservers.Asupervisorthenviewedallofthe videoswithdiscrepanciesinrecordedobservationsof>3betweenobservers.Incasesofclearerror(e.g.2–3observersreported5–7headshakesandoneobserverreported18),thesupervisormadeajudgmentcallon whethertousethemedianresult,removeasingleobserverorremovemultipleobserversforthatobser- vation,sothattherewasonemeasurementforeachcalfateachtime.ActivitymonitoringusingHeyrexVet(Heyrex,Well-ington,NZ)wearablemonitorswasalsoundertaken.AsthisactivitymonitorhasnotbeenvalidatedincalvesthemethodsandresultsaredescribedinSup-plementaryInformation1.2PainsensitivitytestingItwasoriginallyintendedthatpainsensitivitytestingwouldbeconductedat1,2,3,4,6,8,10,12and24hoursafterdisbudding,usingapressurealgometer (FPX50,WagnerInstruments,Greenwich,CT,USA) appliedateightlocationsaroundthehornbud,asshowninFigure2.Thisrequiredplacingthealgometerrubbertipoverthecauterywoundattheedgeofnormaltissue.Howeveronthe rstfarmwherepainsensitivitytestingwascarriedouttheveterinarian

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iredplacingthealgometerrubbertipoverthecauterywoundattheedgeofnormaltissue.Howeveronthe rstfarmwherepainsensitivitytestingwascarriedouttheveterinarian undertakingthetestingimmediatelyexpressed concernaboutthelevelofpainthatthecalveswereexperiencing.Thereforetheplacementofthealg-ometerwaslimitedtopositions1and2oneachhorn bud(Figure2)andtestingwascarriedoutat0–1,2–5,6–11,12and24hoursafterdisbudding.Testingwasconductedwithtwopeoplerestrainingthecalf.Theveterinariancarryingoutthetesting initiallyplacedahandlightlyonthepollofthecalfuntilthecalfwashabituatedtobeingtouchedandstoodstill.Thehandwasthenremovedandreplaced withthealgometerrubbertipatthetwopositionsaroundeachhornbudwound.Theforce(N)thatwasabletobeappliedagainstthewoundbeforethecalf movedawayfromthestimuluswasrecorded. Table2.De nitionsofbehavioursthatwereobservedindairycalvesfollowingcauterydisbudding.BehaviourDescriptionEar ickingCalfrapidlymovesoneorbothearstothefrontandbackindependentofaheadshake.Eachtimemovementconstitutesasanear ick.HeadshakingCalfrapidlyshakesheadfromonesidetotheother.Recordedasonebehaviourwhentheheadmoved slowlyorwasinarestingposition.HeadscratchingCalfliftshindlegtoscratchtopofheadwithfootorrubsheadagainstsidesofthepen. 2https://doi.org/10.1080/00480169.2019.1640651.298 E.CUTTANCEETAL.

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Halfofthecalvesweretestedontherighthorn rst,followedbythelefthorn,withtheremaindertestedintheoppositeorder.Allcalvesreturnedtotypicalfarmmanagement(inonegroup)followingthecompletionofthetrialat24hours.Allanimalhealtheventswere recordedandanyanimalsthatweresu eringillnesseswereremovedfromthetrial.Anycalvesthatexpressed anunusuallyhighaversiontopainsensitivitytesting (struggling,vocalisation)wereremovedfromfurther assessmentsonwelfaregrounds.Inadditiontothealgometermeasurements,thepersonapplyingthealgometeralsosubjectively gradedthecalf’spainresponseaslow,moderate,highorextreme.Themethodsandresultsforthissub- jectiveassessmentarepresentedinSupplementary Information2.3WeightgainAllcalveswereweighedonelectronicweighscaleson Days7and28.FortheDay7visitthecalibrationofthe scaleswasidenti edasbeingincorrectfor30calvesandtheseanimalswereremovedfromweightanalysisforDay7,butwereincludedintheanalysisforDay28.StatisticalanalysesThesamplesizefortotalnumbersofenrolledanimalswasestimatedbasedon95%con dencewith80%powerofdetectingaweightgaindi erencebetweengroups,over28days,of2kgwithavarianceof49kg. Thisresultedin284calvesbeingrequiredacrosssix groups.Anextra80calveswereenrolledduetothelikelihoodoflosinganimalstofollowupafterenrolment.Forthebehaviouralobservationsapproximately90animals,16ineachgroup,wererequiredtodetectan approximate40%di erenceintheincidenceofheadshakesbetweengroups.Approximately132animalswererequiredforthepainsensitivitycomponentof thetrial,todetectadi erencebetweengroupsof7NwithaSDof10N,atanysingletime.BehaviouralobservationDataforthetotalnumberofear icks,headshakesandheadscratchesrecordedat0,1,3,5,7,9,12and

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weengroupsof7NwithaSDof10N,atanysingletime.BehaviouralobservationDataforthetotalnumberofear icks,headshakesandheadscratchesrecordedat0,1,3,5,7,9,12and 22hoursafterdisbuddingwereanalysedseparately.Thedataforear icksandheadscratchesweremod-elledusingtwoseparatemixede ectsnegativebino-mialregressionmodels,wherecalfwastreatedas randome ects,andthenaturallogarithmoflengthofvideorecordedateachtimeperiodwasaddedasano setterm.Forheadshakes,amixede ectsPoissonregressionmodelwitharobuststandarderrorwasadopted,whichalsoincludedcalfasarandome ectandthesameo setterm.Initialexplana-toryvariablesincludedinthemultivariablemodelswerefarm,treatmentgroupandtime,andtheinter-actionbetweentreatmentgroupandtime.Thisinter- actiontermwasincludedasitwaspossiblethatthetreatmentshadadi erentdurationofaction.Startingwithafullmodelthatincludedtheinteractionterm, xede ectsweredroppedfromthemodelifAkaikeinformationcriteriafromthesimplermodelwassmaller.Resultsarereportedasincidencerateratios(IRR),whichcanbeinterpretedastheincrease,or reduction,intherateofthebehaviourperminutepercalf,comparedtoareferencecategory.AnIRR>1.0indicatesanincreaseintherateofabehaviour (i.e.morepainful),andIRR<1.0indicatesareductionintherateofabehaviour(i.e.lesspainful).Nodi erenceswerenotedbetween0,1and3hoursafterdisbudding,sotheseresultswerere-categorised as0–3hoursafterdisbudding.Furtheranalysesofthethreebehaviouralresponseswerecarriedoutusingsimilarmodelstocompareresultsforcalvessedated ornot,treatedwithmeloxicamornot,andtopicalanaestheticornot.PainsensitivityAsmallsubsetofcalveshadanextremesubjectivepainresponseinwhichtheyhead-buttedthealgometer, resultinginaveryhighalgometerreading.Asthesevalueswouldbiastheresults,theywereremovedfromtheanalysis.Resultsfromalgometerreadings recordedatthefourlocationsoneachcalfwere

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algometerreading.Asthesevalueswouldbiastheresults,theywereremovedfromtheanalysis.Resultsfromalgometerreadings recordedatthefourlocationsoneachcalfwere includedintheanalysis,andmeasurementsrecorded Figure2.Diagramshowingthepositionofpressurealgometerplacementformeasurementofpainsensitivityincalvesfollow-ingdisbudding.Theblackovalsindicatethepositionofthe hornbudwoundandthenumbersindicatethelocationforpla- cementofthepressurealgometer. 3https://doi.org/10.1080/00480169.2019.1640651.NEWZEALANDVETERINARYJOURNAL 299

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atdi erenttimeswerere-categorisedas0–1,2–5,6–11and12–24hoursafterdisbudding.Alinearmixedmodel,withcalfasarandome ect,wasusedtoanalysethealgometerreadings.Asitwaslikelythatsedatedcalveswouldbepoorlyrespon-siveimmediatelyafterdisbudding,treatmentgroups wereinitiallycollapsedintosedatedandnon-sedated, andaninteractiontermfortimeandsedationstatuswasaddedtothemodel.Asubsetanalysiswasthenperformedwithresultsfrom0–1hoursremoved,withthesixtreatmentgroups,farm,locationonthecalfandtimeas xede ects.Startingwithafullmodel, xede ectsweredroppedfromthemodelifthelog-likelihoodratiotestbetweentwonestedmodelshad asigni canceofp>0.05.Modeldiagnosticswereexaminedtoassessforoutliersandin uentialobservations.Animportantassumptionoflinearmodellingisthatthevariationoftheresidualsisconstantacrossallrangesofthepredictedoutcomesandassociatedrisk factors.Withthisstudy,thevariationinalgometerread-ingsvariedconsiderablybetweenfarms,withthealg-ometerreadingsbeinggreaterinFarm1thanFarms 2and3,aswasthevariationinthereadings.Thiswascorrectedbymodellingdi erentvarianceweightingsforeachfarm,therebyensuringeachfarmhadequalweightingwhenstandarderrorswereusedtocomparefarms.WeightgainWeightgainwascalculatedforeachcalfastheaveragedailygain(ADG)betweenDays0and7,and betweenDays0and28.Linearregressionmultivari-ablemodelswereusedtoanalysetheADGforeachtimeperiod,includingtheexplanatoryvariablesof farm,treatmentgroupandweightatenrolment.Aninteractiontermbetweentreatmentgroupandfarmwasalsoincludedintheoriginalmultivariable

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eexplanatoryvariablesof farm,treatmentgroupandweightatenrolment.Aninteractiontermbetweentreatmentgroupandfarmwasalsoincludedintheoriginalmultivariable model,asitwasbiologicallyplausiblethatthetreat-mentscouldhavedi erente ectsondi erentfarms.Startingwithafullmodelthatincludedtheinteractionterm, xede ectswereremovedfromthemodelifthelog-likelihoodratiotestbetweentwonestedmodelshadasigni canceofp>0.05.Modeldiagnosticswereexaminedtoassessforout-liersandin uentialobservations.AllstatisticalanalyseswerecarriedoutusingRv3.3.3(RCoreTeam,2017;RFoundationforStatisticalCom- puting,Vienna,Austria),apartfromthenegativebino-mialmodelling,thatwascarriedoutusingStata13(StataCorp,CollegeStation,TX,USA)ResultsThenumberofcalvesenrolledineachtreatmentgrouponthethreefarmispresentedinTable3.Ninecalveswereexcludedfollowingenrolment;onecalfthataspiratedwoodchipswhilstundersedation andeightwerefoundtobepolled.OnefurthercalflostweightbetweenDay7and28,itwasfoundthat thisanimalhadbeenexaminedbyaveterinarianon themorningofDay7andhadbeenidenti edwithdiarrhoeaandill-thrift.Itwasinthesedation-meloxi- camgrouponFarm3andwasexcludedfromthe analysis.BehaviouralresponsesBehaviouralresponseswererecordedandanalysedfor 20,30and44calves,onFarms1,2and3,respectively, acrosseighttimeperiods.Ear icksThemediannumberofear icksperminuteforcalvesineachtreatmentgroupovertimearepresentedin Figure3a.Resultsofthe nalmodelforvariablesassoci-atedwiththenumberofear icksperminuteareshowninTable4.Comparedtocalvesinthecrate-controlgroup,thenumberofear icksperminutewerereducedinallothertreatmentgroups(p≤0.006).Thee ectwassimilarforcalvestreatedwithmeloxicamortopicalanaesthetic.Thenumberofear icksperminutevariedwithtimeafterdisbudding(p<0.001),increasingfrom5–9hoursafterdisbudding,decreasingat12hourswhenthe

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topicalanaesthetic.Thenumberofear icksperminutevariedwithtimeafterdisbudding(p<0.001),increasingfrom5–9hoursafterdisbudding,decreasingat12hourswhenthe majorityofthecalvesweresleeping,thenincreasingagainat22hoursfollowingdisbudding.Therewasnointeractionbetweentimeandtreatmentgroupon thenumberofear icksperminute,indicatingthatthee ectoftreatmentdidnotvarywithtimeafterdisbudding.Thenumberofear icksperminutewashigherincalvesfromFarm1thancalvesfromtheothertwofarms(p≤0.007),buttherewasnointeractionbetweenfarmandtreatmentgroup.HeadscratchesThemediannumberofheadscratchesperminuteforcalvesineachtreatmentgroupovertimearepresentedinFigure3b.Resultsofthe nalmodelforvariablesassociatedwiththenumberofheadscratchesper Table3.Numberofcalvesenrolledonthreefarmsinsixdi erenttreatmentgroupsusedtoinvestigatethee ectofatopicalanaesthetic(TA)ondairycalvesfollowingcauterydisbudding.TreatmentFarm123TotalCrate-control1064763Crate-meloxicam1064662Crate-TA1064662Sedation-control1064460 Sedation-meloxicam964358Sedation-TA1064359Total5936269364300 E.CUTTANCEETAL.

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minuteisshowninTable5.Forcalvesthatweredis-buddedwhilerestrainedinacrate,theadditionofmelox-icamortopicalanaestheticdidnotreducethenumberofheadscratchesperminute(p>0.6),howevertreatmentwithmeloxicamandtopicalanaesthesiainadditionto sedationreducedthenumberofheadscratchesper minutecomparedtocalvesinthecrate-controlgroup(p≤0.013).ThenumberofheadscratchesperminutewashigherincalvesfromFarm1thancalvesfromFarms2or3(p≤0.002).Overall,thenumberofheadscratchesperminutewasreducedby53(95%CI=35–67)%insedatedcalvescomparedtonon-sedatedcalvesacrossthe24-hourperiod(p<0.001). Table4.Resultsofthemixede ectsnegativebinomialregressionmodelforvariablesassociatedwiththenumberofear icksperminuterecordedindairycalves(n=94)onthreefarmsbetween0–22hoursfollowingcauterydisbudding,thatwereallocatedtosixtreatmentgroups(see Table1).VariableIRR95%CIP-valueaIntercept0.040.03–0.06<0.001FarmFarm1RefFarm20.630.46–0.870.005Farm30.660.49–0.890.007Time(hours)0–3Ref51.961.54–2.46<0.00172.291.85–2.84<0.0019b3.652.56–5.20<0.001120.180.12–0.28<0.001222.161.75–2.66<0.001TreatmentCrate-controlRefCrate-meloxicam0.550.37–0800.002Crate-TAc0.540.37–0.780.001Sedation-control0.580.40–0.860.006Sedation-meloxicam0.590.41–0.850.004Sedation-TA0.220.14–0.33<0.001aSigni canceofincidencerateratio(IRR).bThenumberofear icksperminutewas3.65(95%CI=2.56–5.20)timesgreaterat9hoursthanat0–3hours.cThenumberofear icksperminutewas0.54(95%CI=0.37–0.78)timeslowerincalvestreatedwithtopicalanaestheticfollowingdisbuddinginacratethancalvesnottreatedwithtopicalanaesthetic.IRR=Incidentrateratio;Ref=referencecategory;TA=topicalanaesthetic. Figure3.Mediannumberof(a)ear icks,(b)headscratchesand(c)headshakesperminuterecordedincalvesafterdisbud-dingincrateswithnofurthertreatment(redsolidline),orwere

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Mediannumberof(a)ear icks,(b)headscratchesand(c)headshakesperminuterecordedincalvesafterdisbud-dingincrateswithnofurthertreatment(redsolidline),orwere treatedwithmeloxicam(browndottedline),oratopicalanaes- thetic(greendashedline),orweresedatedwithnofurther treatment(turquoisedashedline),orwerealsotreatedwith meloxicam(bluedottedline),oratopicalanaesthetic(pink dashedline). Table5.Resultsofthemixede ectsnegativebinomialregressionmodelforvariablesassociatedwiththenumberof headscratchesperminuterecordedindairycalves(n=94) onthreefarmsbetween0–22hoursfollowingcauterydisbudding,thatwereallocatedtosixtreatmentgroups(see Table1).VariableIRR95%CIP-valueaIntercept0.0020.001–0.003<0.001FarmFarm1RefFarm20.440.27–0.710.001Farm30.510.33–0.780.002Time(hours)0–3Ref51.981.25–3.140.00471.601.06–2.420.0269b2.851.58–5.14<0.001120.380.17–0.850.019221.551.02–2.340.038TreatmentCrate-controlRef Crate-meloxicam1.040.58–1.840.906Crate-TA1.150.66–2.010.63Sedation-control0.620.35–1.110.105Sedation-meloxicam0.470.26–0.850.013Sedation-TAc0.440.23–0.830.011aSigni canceofincidencerateratio(IRR).bThenumberofheadscratchesperminutewas2.85(95%CI=1.58–5.14)timesgreaterat9hoursthanat0–3hours.cThenumberofheadscratchesperminutewas0.44(95%CI=0.23–0.83)timeslowerinsedatedcalvestreatedwithtopicalanaestheticfollowingdisbuddingthancalvesnottreatedwithtopicalanaestheticfollowingdis-buddinginacrate.IRR=Incidentrateratio;Ref=referencecategory;TA=topicalanaesthetic.NEWZEALANDVETERINARYJOURNAL 301

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HeadshakesThemediannumberofheadshakesperminuteovertimeforthesixtreatmentgroupsarepresentedin Figure3c.Inthe nalmixede ectsPoissonregressionmodeltherewasaninteractionbetweentreatment groupandtime(p<0.01).Thereforetheoveralle ectoftreatmentgroupcouldnotbereported.Foralltimesfrom0to12hours,therewasnostat-isticallysigni cantdi erenceintheIRRforeachtreat-mentgroup(p=0.29).However,at22hours,thenumberofheadshakesperminutedi eredbetweentreatmentgroups;comparedtocalvesinthecrate-controlgroup,theIRRforcalvesinthecrate-topicalanaesthesiagroupwas0.43(95%CI=0.20–0.91),forcalvesinthesedation-controlgroupwas0.47(95%CI=0.22–0.99)andforsedation-topicalanaesthesiagroupwas0.16(95%CI=0.06–0.38).Thenumberofheadshakesperminutewas similarforcalvesinthecrate-controlandcrate- meloxicam(p=0.93)andsedation-meloxicam(p=0.08)groups.Thenumberofheadshakesperminutedi eredbetweenfarms(p<0.001).PainsensitivityAtotalof2,469algometertestresultsfrom29,36and 59calvesonFarms1,2and3,respectively,wereused intheanalysis.Therawmeansandrangeofall measurementsrecordedateachtimeperiod,acrossallfarms,foreachofthesixtreatmentgroupsarepre-sentedinTable6.Becausetheyhadanextremepainresponse,andanalgometerreading>40N,25testresultsfromninecalvesonthethreefarmswereremovedfromfurtheranalyses.Forthemodelcomparingpainsensitivitybetweensedatedandnon-sedatedcalvestherewasaninter- actionbetweentimeandtreatment(p<0.001).At0–1hours,calvesthathadbeendisbuddedunderseda-tionhad15.8(95%CI=13.2–18.5)Ngreaterforceappliedtothedisbuddingwoundbeforetheyrespondedcomparedtocalvesthatweredisbudded

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thathadbeendisbuddedunderseda-tionhad15.8(95%CI=13.2–18.5)Ngreaterforceappliedtothedisbuddingwoundbeforetheyrespondedcomparedtocalvesthatweredisbudded andrestrainedinthecrate(p<0.001).Theresultsofthelinearregressionmodelforpainsensitivityaftermeasurementsfrom0–1hourshadbeenexcludedarepresentedinTable7.Therewasstillasigni cante ectofsedation,withamean6.5(95%CI=1.6–11.4)Ngreaterforcebeingappliedtosedatedcalvesbeforetheyshowedawithdrawal responsecomparedtocalvesthatweredisbudded andrestrainedinthecrate(p<0.001).Calvesinallthesedationgroupshadagreaterforceappliedbeforetheyrespondedthanthecalvesinthecrate- controlgroup(p<0.01),howeverresponseswere similarbetweencalvesthatweregivenmeloxicamortopicalanaestheticineitherthecrateorsedationgroups.Therewasnostatisticallysigni cantdi er-encebetweenpainsensitivityincalvesinthecrate-meloxicamorcrate-topicalanaesthesiagroupsincomparisontothecrate-controlgroup(p >0.4).Theforcerequiredtoelicitaresponsewaslowerbetween6–11hoursafterdisbuddingcomparedto22–24hoursafterdisbudding,indicatingareducedpainsensitivityby24hours. Table6.Mean(min,max)algometerreadings(N)forallpainsensitivitymeasurementsindairycalves(n=124)onthreefarmsbetween0–24hoursfollowingcauterydisbudding,thatwereallocatedtosixtreatmentgroups(seeTable1).Treatment0–1hour2–5hours6–11hours12–24hoursCrate-control25.7(0.2,73.2)17.5(0.6,79.8)16.1(0.2,66.0)24.6(2.4,83.2)Crate-meloxicam21.9(0,70.2)21.3(1.0,87.6)18.6(0.6,86.8)25.8(1.6,66.8)Crate-TA27.4(0,64.8)22.0(0.2,76.4)17.7(0.4,61.0)25.2(1.6,66.8)Sedation-control38.6(11.7,86.0)26.7(3.6,77.6)22.2(0.2,82.4)29.9(3.4,79)Sedation-meloxicam40.8(3.6,89.2)31.8(2.0,93.8)25.2(0.2,99.8)29.9(3.4,89.0)Sedation-TA42.5(4.2,94.6)36.4(3.4,100.4)23.5(1.4,84.2)30.0(2.8,84.0)TA=Topicalanaesthetic.

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icam40.8(3.6,89.2)31.8(2.0,93.8)25.2(0.2,99.8)29.9(3.4,89.0)Sedation-TA42.5(4.2,94.6)36.4(3.4,100.4)23.5(1.4,84.2)30.0(2.8,84.0)TA=Topicalanaesthetic. Table7.Resultsofthelinearregressionmodelforvariablesassociatedwithalgometerreadings(N)forpainsensitivityrecordedindairycalves(n=1,828measurementsfrom124 calves)onthreefarmsbetween2–24hoursfollowingcauterydisbudding,thatwereallocatedtosixtreatmentgroups(see Table1).VariableEstimate95%CIP-valueaIntercept15.52TreatmentCrate-controlRefCrate-meloxicam1.09−3.63–5.800.65Crate-TA1.89−2.98–6.750.45Sedation-control6.51.64–11.350.01Sedation-meloxicam8.483.61–13.35<0.001Sedation-TAb9.104.30–13.90<0.001FarmFarm1RefFarm2−3.5−7.23–0.230.07Farm315.4211.92–18.92<0.001Time(hours)12–24Ref2–52.821.41–4.24<0.0016–11c−5.31−6.37to−4.25<0.001LocationLefttopRef Leftside−5.53−6.80to−4.25<0.001Righttop4.853.56–6.13<0.001Rightside−1.03−2.31–0.250.11aSigni canceofestimate.bTheforcerequiredtoelicitapainresponsewas9.10(95%CI=4.30–13.90)Ngreaterforsedatedcalvestreatedwithtopicalanaestheticfollowingdisbuddingthanforcalvesnottreatedwithtopicalanaestheticfollowing disbuddinginacrate.cTheforcerequiredtoelicitapainresponsewas5.31(95%CI=4.25–6.37)Nlessforcalvestestedbetween6–11hoursafterdisbuddingthanforcalvestestedat22–24hours.Ref=referencecategory;TA=topicalanaesthetic.302 E.CUTTANCEETAL.

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WeightgainTheADGofcalvesbetweenDays0–7wasanalysedin310calvesandbetweenDays0–28in315calves.Days0–7AveragedailygainbetweenDays0–7variedbetweenthetreatmentgroups(SupplementaryTable2)4,withtheADGofcalvesinthesedation-meloxicamgroupbeing0.14(95%CI=0.015–0.274)kg/daygreaterthancalvesinthecrate-controlgroup.Growthratesweresimilarbetweenfarms,andtherewasnointer- actionbetweentreatmentgroupandfarm.Weight atenrolmentwasnotassociatedwithADGbetweenDays0–7.Whencomparingsedatedandnon-sedatedcalves,theADGofcalvesdisbuddedundersedationwas0.10(95%CI=0.02–0.17)kg/daymorethancalvesdis-buddedinacrate(p=0.009).Howevertherewas nooveralle ectofeithertopicalanaesthesia(p=0.50),ormeloxicam(p=0.75)onADGbetweenDays0–7.Days0–28TheADGofcalvesbetweenDays0–28variedbetweenfarms(p<0.05),buttherewasnofarmbytreatmentinteraction(p=0.73;SupplementaryTable3).4TheADGofcalvesinthesedation-topicalanaesthetic grouptendedtobegreaterthancalvesinthecrate-controlgroupby0.06(95%CI=−0.01–0.13)kg/day(p=0.09).Therewasnostatisticallysigni cantdi erenceinADGbetweenanyoftheothertreatmentgroups comparedtothecrate-controlgroup.Whencomparingsedatedandnon-sedatedcalves,theADGofsedatedcalveswas0.05(95%CI=0.01–0.09)kg/daygreaterthannon-sedatedcalves(p=0.01).Therewasnooveralle ectofeithertopicalanaesthetic(p=0.82),ormeloxicam(p=0.74),on ADGbetweenDays0–28.DiscussionThisstudyisoneofthelargeststudiesconductedondisbuddingandshowedthattherewasapositivee ectofdisbuddingundersedationonalloutcomesmeasured.Therewasabene ttoprovidingcalveswithtopicalanaestheticormeloxicamfollowingdis- buddingonbehaviouralresponsesandpainsensitivity.

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nonalloutcomesmeasured.Therewasabene ttoprovidingcalveswithtopicalanaestheticormeloxicamfollowingdis- buddingonbehaviouralresponsesandpainsensitivity. Thebene toftopicalanaestheticwasnotstatisticallydi erenttothatofmeloxicamexceptforareductioninear icksinsedatedcalves.Paincanbedi culttomeasureasitisasubjectivestate.Howeverbehaviourcanbeasensitiveindicatorofpain,overandabovethatofconcentrationsofcorti-solinserumandotherphysiologicalmeasures(Aniletal.2002).Behaviouralresponsessuchasthosemeasuredinthisstudyareanacceptedindicatorof painresultingfromadisbuddingprocedure(Faulkner andWeary2000;Sta ordetal.2003;Heinrichetal.2010).Thebehaviouralobservationsprovidedanimportantinsightintothebehaviourofcalvesfor 24hoursfollowingdisbudding.Despitetheuseofa cornualnerveblock,theobservationsofear icks,headshakesandheadscratchesindicatedthatthe painexperiencedbycalvesinthe rst24hoursafterdisbuddingwassubstantial.Boththeuseofmeloxicamortopicalanaestheticresultedinareductionofear icks,incalvesthatweredisbuddedinacrateorsedated.However,themostpronouncedreductionwasseenincalvestreatedwiththecombinationofsedationandtopical anaestheticwhichresultedina78%reductioninear icksanda56%reductioninheadscratchesrelativetocalvesdisbuddedinacratewithoutsedation.Theequivalentreductionincalvestreatedwithmeloxicam plussedationwas41%and53%forear icksandheadscratches,respectively.Itispossiblethatbecausecalveswithinthesixtreat-mentgroupswereobservedforbehaviouralresponseswithinthesamepen,therecouldbeaperceivedlackofindependencebetweencalves.Forhealthycalvesnot

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hinthesixtreat-mentgroupswereobservedforbehaviouralresponseswithinthesamepen,therecouldbeaperceivedlackofindependencebetweencalves.Forhealthycalvesnot experiencingpain,ifaparticularlyactivecalfwaspresentitmayin uencethebehaviourofothercalvesinapen.Howeverinthisstudyveryspeci cbehaviourresponseswereassessedthathavebeendemonstratedtobeindicatorsofpain(FaulknerandWeary2000;Sta ordetal.2003;Heinrichetal.2010).Itwasconsideredveryunlikelythatear icks,headscratchesorheadshakesofonecalfwouldin uencetheexpressionofthesebehavioursinothercalveswithinapen,sotheyweretreatedasindependent observations.Practically,theseresultssuggestthatifcalvesaredisbuddedbylaydisbuddingoperationsorby farmers(whocannotusesedation),thereissomebene tofusingtopicalanaestheticormeloxicam,buttominimisethepain-associatedbehavioursafterdis-budding,sedationisrequired.Thisstudyhasprovided someevidence(basedonear icksandheadshakes)thataddingtopicalanaesthetictoadisbuddingpro- cedurethatinvolvedsedationreducedtheexpressionofpain-associatedbehaviourscomparedtouseofmeloxicam.Inadditionthereappearedtobeanextendede ectoftopicalanaestheticinreducingthenumberofheadshakesat22hoursincalvesdis- buddedwithandwithoutsedation.Sedationalonealsoreducedthenumberofheadshakesatthistime, buttheuseofmeloxicamdidnot.Thebene tofsedationmaybeadirecte ectoftheanalgesice ectofxylazine,themoderationof 4https://doi.org/10.1080/00480169.2019.1640651.NEWZEALANDVETERINARYJOURNAL 303

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hyperalgesiaorreducedanxiety(Garcia-Villaretal.1981;Browningetal.1982),buttherearesomeotherreasonsforthestronge ectofsedationseeninthisstudy.Firstly,tosimplifystudymanagement,thesedatedcalveswerekeptseparatefromtheunsedatedcalves.Thismeantthatonetechnicianprovidedthe cornualnerveblocktosedatedcalvesandanotherto thecalvesdisbuddedinacrate.Thusitispossiblethatthisconfoundingbetweensedationandtech-niciancouldhavecontributedtotheapparente ectofsedationiftheirtechniquesweredi erent.Howeverthetechnicianswereextremelyexperienced andtrainedannuallytotheveterinaryclinic’sstandardoperatingprocedure,andhadalsobeenretrainedbythesupervisingveterinarianpriortostudystart.Fur-thermorethee ectivenessofallthecornualnerveblockswerecheckedpriortodisbudding.Anotherpotentialreasonfortheapparentbene tofsedationwasthatitwouldhavebeeneasiertoadministerthenerveblockincalvesthatweresedatedthanrestrained inacrate.Thereforethebene tsobservedafterdisbud-dingmayhavebeenduetomoree ectiveanalgesiaduringthedisbuddingandnotnecessarilyjustthe e ectofxylazine.Responsesofcalvesduringdisbud-dingwerenotrecorded,andwereonlyusedasanindi- cationthatananimaldidnothaveane ectiveblock(asperthedisbuddingprotocol),butcouldhavehadarelationshipwiththesubsequentlyrecordedresponses.Althoughtherearenosuitablecomparablestudiesontheuseofatopicalanaestheticfollowingdisbud-dingwithacornualnerveblock,theresultsarecompar-abletootherstudiesthathaveinvestigated behaviouralresponsesfollowingtheuseofNSAID.Heinrichetal.(2010),comparedtheuseofmeloxicamandaplacebofollowingdisbuddingwithacornualnerveblockandreportedreductionsinear ickperhourof70%and83%withmeloxicam0and1days afterdisbudding,respectively.Therewasalsoa74%

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ngdisbuddingwithacornualnerveblockandreportedreductionsinear ickperhourof70%and83%withmeloxicam0and1days afterdisbudding,respectively.Therewasalsoa74% reductioninheadshakesbutnoreductioninheadscratches.FaulknerandWeary(2000)comparedbehav-iouralresponsesincalvesdisbuddedwithacornualnerveblockandsedationaswellastreatedwithketo- profenwithcalvesnottreatedwithketoprofen.Theyfoundasigni cantreductioninthefrequencyofear icks,headshakesandheadrubsduringthe24hoursafterdisbuddingincalvestreatedwithketoprofen. Theseresults,aswellasourstudyresults,indicatethatthebehaviouralresponsesofcalveswhoreceived topicalanaestheticwascomparabletothebehaviouralresponsesofcalveswhoreceivedNSAID.Theuseofpressurealgometryhaspreviouslybeenusedinadultcattletoobjectivelyassesspainassoci- atedwithskinlesionsoflamecattle(Dyeretal.2007)aswellastoassessthepainassociatedwithdehorning.(Heinrichetal.2010).Thee ectoftopicalanaestheticandmeloxicamonthepainsensitivity,asmeasuredwiththepressurealgometer,wasonlyapparentincalvesthatweresedatedandwascomparablebetweenthetwoproducts,andweresimilartothose ofcalvesthatthatwereonlysedated.Theseresultsweresupportedbythesubjectivepainassessment,wheresedatedcalveshadsigni cantlyreducedoddsofshowinghighorextremeresponsescompared withunsedatedcalves.Thee ectofprovidingpainreliefusingNSAIDonweightgainafterdisbuddingwasinvestigatedintwostudies(Batesetal.2015,2016),whichfoundthattreat-mentwithmeloxicamorketoprofenwasassociated withincreasedweightgainonlyinanimalsdisbudded withoutsedationorlocalanaesthetic.Therewasnobene tifNSAIDwereusedalongsidesedationandlocalanaesthetic.Incontrastthepresentstudyshowedasigni cantincreaseinweightgaininthe rst7daysafterdisbudding,onlyinsedatedcalvestreatedwithmeloxicamcomparedtothecrate- controlgroup.However,theseresultsarenotdirectly

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seinweightgaininthe rst7daysafterdisbudding,onlyinsedatedcalvestreatedwithmeloxicamcomparedtothecrate- controlgroup.However,theseresultsarenotdirectly comparablewiththoseofthepreviousstudies,asinthepresentstudyallanimalshadacornualnerveblockwhichcouldhavereducedanypotentialimpact ofmeloxicamongrowthrates.Nevertheless,ourresultsareconsistentwiththoseofBatesetal.(2015,2016)astheincreasedgrowthratesrecordedinthe7daysafterdisbuddinginsedatedcalvestreatedwith meloxicam(0.144kg/day)wereonlymarginallygreaterthantheincreaseseenincalvesintheseda- tion-controlgroup(0.125kg/day).This ndingsupportsthesuggestionthattheuseofxylazinesedationalonemayincreaseweightgainafterdisbudding(Batesetal.2015,2016).Oneofthepracticalconsiderationsofusingthetopicalanaestheticwasthatitwasaliquid.Inthestudy,theproductwasappliedandanysurplusliquid wascaughtonatowelbeforethecalfwasreleased.Thismaypossiblyhavegivenalongercontacttimefortheproduct,butitisunknownifthiswoulda ecthowwellitwase ective.Managementofanimalwelfareneedstobeattheforefrontofourdairyindustryandthisstudyhas givenastrongindicationthat,untilweareabletopre- dominantlybreedpolledcalves,morecanbedonetoalleviatepainandsu eringfollowingthedisbuddingprocedure.Thepositiveresultsshownfromtheuseofthetopicalanaestheticincombinationwithsedationindicatethatthisproductproducesane ectivereductioninindicatorsofpain,similartothoseresult-ingfromuseofNSAID.Inconclusion,therewasapositivee ectofdisbud-dingcalvesundersedationonalloutcomes.Therewas abene ttoprovidingcalveswithtopicalanaestheticfollowingdisbuddingonbehaviouralresponsesand painsensitivityandthisbene twasnotstatisticallydi erenttothatoftreatmentwithmeloxicam.Thee ectsweremostpronouncedwhentopical304 E.CUTTANCEETAL.

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anaestheticwasappliedincalvesthatweredisbuddedundersedationandindicatethatthee ectmaylastatleast22hoursfollowingthedisbuddingprocedure.AcknowledgementsTheauthorswouldliketothankBayerNewZealandLtdforfundingthestudy,thefarmanimalowners,managersand workersforallthetimetheyspentdrafting,helpingmake pensand nallytheamazingVetEnttechniciansandvetsfortheirorganisation, exibilityandmostofall,enthusiasm.ORCIDELCuttance http://orcid.org/0000-0003-0354-5295DAYang http://orcid.org/0000-0003-3893-9403RALaven http://orcid.org/0000-0002-8938-8595References*Anonymous.AnimalWelfare(CareandProcedures)Regulations2018http://www.legislation.govt.nz/regulation/public/2018/0050/latest/096be8ed817efd82. pdf(accessed1June2019).NewZealandGovernment,Wellington,NZ,2018AnilSS,AnilL,DeenJ.Challengesofpainassessmentindomesticanimals.JournaloftheAmericanVeterinaryMedicalAssociation220,313–9,2002BatesAJ,EderP,LavenRA.E ectofanalgesiaandanti-in ammatorytreatmentonweightgainandmilkintakeofdairycalvesafterdisbudding.NewZealandVeterinaryJournal63,153–7,2015BatesA,LavenR,ChappleF,WeeksD.Thee ectofdi erentcombinationsoflocalanaesthesia,sedativeandnon-steroidalanti-in ammatorydrugsondailygrowthratesofdairycalvesafterdisbudding.NewZealandVeterinaryJournal,64,282–7,2016BrowningS,LawrenceD,LivingstonA,MorrisB.Interactionsofdrugsactiveatopiatereceptorsanddrugs activeatα2receptorsonvarioustestsystems.BritishJournalofPharmacology77,487–91,1982DyerRM,NeerchalNK,TaschU,WuY,DyerP,RajkondawarPG.ObjectivedeterminationofclawpainandItsrelationshiptolimblocomotionscoreindairy cattle.JournalofDairyScience90,4592–602,2007EspinozaC,LomaxS,WindsorP.Thee ectofatopicalanestheticonthesensitivityofcalfdehorningwounds.

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