Evaluating the efficacy of a topical anaesthetic formulation and ketoprofen, alone and in combination, on the pain sensitivity of dehorning wounds in Holstein-Friesian calves

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CSIRO PUBLISHING Animal Production Science http://dx.doi.org/10.1071/AN14012 Evaluating the efficacy of a topical anaesthetic formulation and ketoprofen, alone and in combination, on the pain sensitivity of dehorning wounds in Holstein-Friesian calves Crystal A. Espinoza A, Dominique McCarthy A, Peter J. White A, Peter A. Windsor A and Sabrina H. Lomax A,B A Faculty of Veterinary Science, The University of Sydney, NSW 2006, Australia. B Corresponding author. Email: sabrina.lomax@sydney.edu.au Abstract. The aim of this study was to investigate the effect of a topically applied local anaesthetic and the non-steroidal anti-inflammatory drug ketoprofen, alone and in combination, on the pain sensitivity response of calves to dehorning (mean age 2.2 months). Calves were randomly allocated and blocked by age to one of four groups. Groups were: scoop dehorning (D, n = 8), scoop dehorning + i.m. administration of 3 mg/kg ketoprofen (DK, n = 8), scoop dehorning + application of topical anaesthetic (DTA, n = 7) and scoop dehorning + application of topical anaesthetic and i.m. administration of ketoprofen (DKTA, n = 7). A pressure algometer was used to determine the mechanical nociceptive threshold (MNT), being the pressure (kg/f) at which calves withdrew from the stimulus. Measurements were taken before dehorning and at 1 min, 1, 2, 5 and 24 h post-dehorning at both the cut skin edge of the wound and the peri-wound area. The effect of treatment changed over time (P < 0.001). MNT was highest before treatment (MNT = 5.03 kg/f) and tended to decrease over time (MNT = 1.16 kg/f 24 h post-treatment). Overall, D calves exhibited the lowest MNT with an average of 1.77 kg/f. DTA calves had the highest MNT (3.89 kg/f), followed closely by DKTA calves (3.24 kg/f). DK calves exhibited an

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west MNT with an average of 1.77 kg/f. DTA calves had the highest MNT (3.89 kg/f), followed closely by DKTA calves (3.24 kg/f). DK calves exhibited an intermediate MNT of 2.61 kg/f. MNT of the cut skin edge was generally lower than that of the peri-wound area (2.01 vs 3.81 kg/f, respectively, P = 0.02).The topical anaesthetic formulation significantly reduced the pain sensitivity of dehorning wounds. There was no observed enhanced analgesic effect with addition of ketoprofen. The cut skin edge was more sensitive to pressure than the peri-wound area. Additional keywords: calf, non-steroidal anti-inflammatory drug, topical anaesthesia, welfare. Received 12 January 2014, accepted 15 February 2015, published online .BZ Introduction beef producers. In the interim, pain management is one realistic Dehorning is a common procedure in the dairy and beef cattle alternative to allay welfare concerns at dehorning (Fisher et al. industries and is well documented as being painful (Fisher et al. 2008). Although dehorning is traditionally performed without 2008). It is an important management tool for production and pain relief in many countries (Huxley and Whay 2006; Fisher safety reasons. Apart from increased probability of injury and et al. 2008; Paull et al. 2009), changing legislation especially difficulty in handling, horns may have additional economic in the EU recommends pain relief be used for calves over impacts through bruising and hide damage to other cattle, and 4 weeks of age (Council of Europe 1988). Research has been increased requirements for space during feeding and transport conducted on the application of anaesthesia and analgesia for (Vowles 1976; Marshall 1977; Stookey and Goonewardene the procedure, however the cost-effectiveness and practicality of 1996;

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thesia and analgesia for (Vowles 1976; Marshall 1977; Stookey and Goonewardene the procedure, however the cost-effectiveness and practicality of 1996; Stafford and Mellor 2005). Dehorning cattle reduces this approach for routine on-farm use is questionable (Petherick bruise trim by ~50% thus helping to reduce economic losses 2005). Studies on the attitudes of producers and practitioners (Prayaga 2007). to pain alleviation when dehorning, have shown that the main Despite the justifications for dehorning, there is growing reasons for lack of use of anaesthesia and analgesia were time public concern for production animal welfare, including the constraints, cost, and lack of information or skill (Huxley and welfare of animals undergoing painful husbandry procedures Whay 2006; Gottardo et al. 2011; Guatteo et al. 2012). (Fisher et al. 2008). This requires evaluation of alternative Regardless of existing constraints and limitations, there is options to dehorning or modification of the dehorning evidence that livestock industries are responding to welfare procedure to reduce or eliminate pain. Although the long-term concerns, with consideration of pain relief for calves solution to dehorning is the breeding of polled cattle, this is undergoing dehorning. Legislation requiring the administration currently not a feasible or practical solution for many dairy and of local anaesthesia before castration and dehorning has been Journal compilation ! CSIRO 2015 www.publish.csiro.au/journals/an B Animal Production Science C. A. Espinoza et al. enacted by several European countries (Graf and Senn 1999; Algometry has also been previously validated as a tool to quantify Rollin 2004). The Farm Animal Welfare Council in the UK pain sensitivity following dehorning (Heinrich et al. 2010;

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ly validated as a tool to quantify Rollin 2004). The Farm Animal Welfare Council in the UK pain sensitivity following dehorning (Heinrich et al. 2010; recommends that analgesics and local anaesthesia be used Tapper 2011). Calves undergoing cautery disbudding were when dehorning calves, and that the procedure be performed found to have lower MNT than calves that had not been before 2 months of age (Anonymous 1997). ‘The Australian disbudded, suggesting that the procedure causes a pain Model Code of Practice for the Welfare of Animals: Cattle’ response (Heinrich et al. 2010). It was also found that calves encourages dehorning as young as possible and recommends that were dehorned following administration of meloxicam, the use of a local anaesthetic when dehorning calves over had higher MNT than calves that were dehorned without 6 months of age (Anonymous 2004a). The Australian analgesia, suggesting that meloxicam helped to relieve the Veterinary Association also states that cattle should be pain response (Heinrich et al. 2010). dehorned as young as possible and that analgesia should be This experiment aimed to investigate the duration and effect used where appropriate (Anonymous 2004b). of a topical anaesthetic and the NSAID ketoprofen, alone and in Issues of impracticality and cost of pain relief for dehorning combination, on the pain sensitivity of calves undergoing scoop can be addressed through the introduction of a topical anaesthetic dehorning. It was hypothesised that calves receiving the topical that can be easily applied on-farm by producers. Recently, a anaesthetic and ketoprofen would exhibit lower pain sensitivity topical anaesthetic wound dressing was shown to significantly than calves dehorned alone, and that their combined use would reduce short-term

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nsitivity topical anaesthetic wound dressing was shown to significantly than calves dehorned alone, and that their combined use would reduce short-term pain sensitivity in scoop dehorned dairy calves result in an additive effect on pain sensitivity. (Espinoza et al. 2013). This multipurpose formulation contained lignocaine and bupivacaine for local anaesthesia, cetrimide for Materials and methods antisepsis, and aluminium chlorohydrate for astringency of the Animals and housing wound. These ingredients were carried in a viscous gel base to improve adhesion to the wound and surrounding tissue. Thirty Holstein-Friesian heifer calves (51–86 days old) were Lignocaine, when administered as a cornual nerve block or a sourced from ‘Corstophine’ Dairy Unit at The University of ring block, provides rapid onset of anaesthesia at 2–5 min after Sydney (New South Wales, Australia) in May 2013. The application, and the anaesthetic effects are documented to last calves had been raised under commercial dairy operational up to 3 h (McMeekan et al. 1999; Faulkner and Weary 2000; conditions. The experimental protocol was conducted under Stafford and Mellor 2005; Stewart et al. 2009; Coetzee 2011). institutional animal ethics committee approval (Approval No. Bupivacaine is a longer acting local anaesthetic that begins to 5832). take effect 20–30 min after administration, with anaesthesia Calf weights were estimated using a Holstein-Friesian dairy lasting up to 8 h (Faulkner and Weary 2000; Stafford and calf weight estimation tape (The Coburn Co., Inc., Whitewater, Mellor 2005; Coetzee 2011). Although the use of injected WI, USA) with a range of 65.5–122.3 kg. Horn bud diameter local anaesthetic agents has been well documented, their (cm) for each calf was measured using a

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USA) with a range of 65.5–122.3 kg. Horn bud diameter local anaesthetic agents has been well documented, their (cm) for each calf was measured using a standard metric ruler. topical application requires further examination. Diameter was set as the distance across the base of the horn Non-steroidal anti-inflammatory drugs (NSAID) have where it attached to the skull. Calves were group-housed in analgesic effects that extend into the post-operative period by 50 · 20-m paddocks from 2 days of age and for the duration inhibiting cyclooxygenase and prostaglandin production and of the experimental period. The calves were fed a milk ration at reducing nociceptor sensitisation (Coetzee 2011). Subcutaneous ~10% of their bodyweight twice daily at 0730 hours and 1530 infiltration with a local anaesthetic, in combination with the hours via an artificial teat and had ad libitum access to water NSAID ketoprofen, has been shown to reduce the cortisol and kikuyu-based pasture. response, pain-related behaviour, and heart rate in calves undergoing dehorning to a greater degree than local Experimental design and treatments anaesthesia alone (Faulkner and Weary 2000; Stafford and On the day of the experiment, calves were randomly allocated Mellor 2005; Coetzee 2011). Thus, if used in combination to one of four treatment groups: (1) scoop dehorning (D, n = 8), with a topical anaesthetic, the inclusion of an NSAID may (2) scoop dehorning with pre-operative administration of provide enhanced relief of the pain associated with dehorning. ketoprofen (3 mg/kg) (Key Injection, Parnell Technologies NZ Algometry is a form of quantitative sensory testing that Pty Ltd, Auckland) (DK, n = 8), (3) scoop dehorning with post- provides objective, repeatable results (Duarte et al. 2005) operative

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sory testing that Pty Ltd, Auckland) (DK, n = 8), (3) scoop dehorning with post- provides objective, repeatable results (Duarte et al. 2005) operative application of topical anaesthetic (TA) (Technical when measuring sensation, pain detection and pain tolerance Consultancy Services Pty Ltd, Rockdale, NSW, Australia) (Clark et al. 2011). An algometer applies increasing pressure (DTA, n = 7) and (4) scoop dehorning with pre-operative onto a target site and measures the pressure, usually in kilograms administration of ketoprofen and post-operative application of or pounds of force, at which the animal withdraws from the TA (DKTA, n = 7). The experiment was conducted over 2 days, stimulus (Clark et al. 2011). The maximum pressure applied is with 16 calves being treated on the first day (D and DK treatment interpreted as the pain threshold response (or mechanical groups) and 14 calves being treated on the second day (DTA nociceptive threshold; MNT) of the animal (Fitzpatrick et al. and DKTA treatment groups). Calves were quietly moved from 2013). Algometry has been used to successfully provide an their housing paddocks to a holding pen. Ketoprofen was indication of pain in a variety of conditions in cattle including administered intramuscularly in the neck 20 min before lameness, digital dermatitis, ocular pain in calves affected with dehorning at a dosage of 3 mg/kg. All calves that did not bovine keratoconjunctivitis, and mastitis (Dyer et al. 2007; receive ketoprofen (D and DTA calves) were administered a Cutler et al. 2013; Fitzpatrick et al. 2013; Dewell et al. 2014). placebo injection of buffered saline intramuscularly in the Topical anaesthesia for dehorning in calves Animal Production Science C neck equivalent to the volume it would have received if given

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uscularly in the Topical anaesthesia for dehorning in calves Animal Production Science C neck equivalent to the volume it would have received if given ketoprofen. This was conducted to eliminate any possible effect the injection may have on the calves’ pain sensitivity. Individual calves were then moved through the race and restrained in a standing upright position in a calf cradle (Arrow Farmquip, Tamworth, NSW, Australia) for treatment and data collection. Scoop dehorning was performed by a single experienced technician. The dehorning device was positioned over the horn bud and the handles pulled apart to excise the horn bud and surrounding tissue. TA was administered immediately after dehorning with a 10-mL syringe and a soft silicone brush. Approximately 7 mL of TA was applied per wound (~14 mL per calf), or enough to completely cover the dehorned wound and the peri-wound area. The peri-wound area covered by TA was ~1 cm wide for the total circumference of the dehorned wound. The brush was cleaned between calves in a bucket of 100 mL/L chlorhexidine solution (Hibitane, Coopers Animal Health, Sydney, NSW, Australia). Following treatment and Fig. 1. Sites subjected to pressure sensitivity testing (peri-wound sites: data collection, calves were quietly returned to their paddocks black stars; cut skin edge sites: grey stars). until subsequent data collection was required, where they were quietly moved back to the holding pen and cradle. differentiate between calves that had been treated with TA and those that had not. Assessment of pressure/pain threshold Statistical analyses Pressure algometry was used to measure changes in pain sensitivity over time, with the amount of force required to Data was normalised by log-e transformation. Pressure readings elicit a head

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anges in pain sensitivity over time, with the amount of force required to Data was normalised by log-e transformation. Pressure readings elicit a head withdrawal response denoted as the MNT (in were analysed by conducting residual maximum likelihood using kg/f). This value can also be interpreted as the minimum the statistical software package, GENSTAT (VSN International Ltd, pressure required to induce a pain response. For this Hemel Hempstead, UK). The fixed effects of the model were experiment, a pain response was defined as a full head treatment (D, DK, DTA, DKTA), time (pre-treatment, 1 min, 1, 2, withdrawal reflex away from the mechanical stimulus. Testing 5, and 24 h post-treatment), and their interaction, area tested was performed using a calibrated hand-held pressure algometer (peri-wound or cut skin edge), calf weight and age, and horn (Wagner Pain Test FPIX Digital Algometer, Wagner Instruments, bud diameter. The random effect of the model was calf. For Riverside, CT, USA) with a maximum threshold of 10 kg all statistical calculations, P-values !0.05 were considered force (to 50 g accuracy). Measurements were taken after each statistically significant. calf had settled in the calf cradle and there was minimal noise or external activity to distract the animal. The algometer, Results equipped with a round rubber tip ~1 cm in diameter, was Overall placed perpendicular to the target site for each measurement. There was a significant interactive effect of time and treatment Increasing pressure was slowly applied until the calf withdrew (P < 0.001), and area tested and treatment (P = 0.02) on MNT. its head, and the maximum pressure applied was recorded as There was no significant effect of calf age, weight or horn bud the MNT (kg/f). Calves that did not

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d, and the maximum pressure applied was recorded as There was no significant effect of calf age, weight or horn bud the MNT (kg/f). Calves that did not respond to pressure testing diameter on MNT. had its MNT recorded as 10 kg/f (maximum threshold of the algometer). The algometer was reset to zero after each pressure sensitivity test. Time and treatment interactive effect Pressure sensitivity was measured immediately before There was a significant effect of time and treatment, and a dehorning, and 1 min, 1 and, 2, 5 and 24 h post-dehorning. significant time and treatment interaction (P < 0.001). All The algometer was operated throughout the experiment by a calves had an MNT between 4.44 and 6.12 kg/f before single and trained technician. Pressure measurements were treatment (mean 5.03 kg/f) (Fig. 2). Thereafter MNT decreased taken from eight sites on each calf in total: four sites located over time reaching the lowest mean MNT at 24 h post-treatment. on the cut skin edge of the wound and four sites located on the Overall, D calves exhibited the lowest MNT with an average of surrounding tissue (peri-wound area ~1 cm from the cut skin 1.77 kg/f. DK calves had a mean MNT of 2.61 kg/f. DTA calves edge) (Fig. 1). The cut skin edge sites were chosen as it has had the highest mean MNT (3.89 kg/f), followed closely by previously been shown that the sensitivity of cut skin edges in DKTA calves (3.24 kg/f). mulesing wounds are more sensitive to pain due to damaged D versus DK At 1 min post-dehorning, the mean MNT of DK nerve endings (Lomax et al. 2008). The peri-wound sites were calves was greater than that of D calves (5.22 and 3.65 kg/f, chosen to investigate secondary hyperalgesia (exaggerated pain respectively). At 1 and 2 h post-treatment, DK calves had a response in

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and 3.65 kg/f, chosen to investigate secondary hyperalgesia (exaggerated pain respectively). At 1 and 2 h post-treatment, DK calves had a response in tissue surrounding the wound). The visibility of the significantly greater mean MNT than D calves (P < 0.05). Mean TA on the wound surface meant that the technician was able to MNT of these calves were similar 5 and 24 h post-treatment. D Animal Production Science C. A. Espinoza et al. 9 Dehorned Dehorned + Ketoprofen Dehorned + Topical Anaesthetic 8 Dehorned + Ketoprofen + Topical Anaesthetic Mean mechanical nociceptive threshold (kg/f) 7 b a 6 a b ab 5 a c ab 4 a b c c 3 a ab bc 2 b a ab a a 1 a a a a 0 Pre 1 min 1h 2h 5h 24 h Time Fig. 2. Predicted mean mechanical nociceptive thresholds following algometer mechanical stimulation on various sites over time on the peri-wound and cut skin edge of dehorned calves subjected to the following treatments: dehorned alone (n = 8), dehorned with ketoprofen (n = 8) dehorned and treated with topical anaesthesia (n = 7), and dehorned with ketoprofen and treated with topical anaesthesia (n = 7). Calves not sharing the same superscript within each time point are considered statistically significant (P < 0.05). D versus DTA The mean MNT of DTA calves was 7 significantly higher than D calves at all time points post- Peri-wound a treatment except 24 h (P < 0.05). 6 Skin-edge Mean mechanical nociceptive D versus DKTA The mean MNT of DKTA calves was greater a 5 than that of D calves at all time points, with significant differences threshold (kg/f) a 2 and 5 h post-treatment (P < 0.05). 4 b DK versus DTA MNT was numerically higher in DTA than a b DK calves at most time points, with a significant difference 3 detected 2 h post-treatment (P < 0.05). b DK versus DKTA MNT of DK and DKTA

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DTA than a b DK calves at most time points, with a significant difference 3 detected 2 h post-treatment (P < 0.05). b DK versus DKTA MNT of DK and DKTA calves were similar 2 1 min, 1 and 24 h post-treatment. DKTA calves had significantly b greater MNT than DK calves 2 and 5 h post-treatment (P < 0.05). 1 DTA versus DKTA MNT was numerically higher in DTA 0 than DKTA calves 1 min, 1, 2 and 24 h post-treatment. MNT D DK DTA DKTA was numerically higher in DKTA than DTA calves 5 h post- treatment. No significant differences were detected between Fig. 3. Predicted mean mechanical nociceptive thresholds following groups at any time point. algometer mechanical stimulation on the peri-wound and cut skin edge of dehorned calves subjected to the following treatments: dehorned alone (D) (n = 8), dehorned with ketoprofen (DK) (n = 8), dehorned and treated with topical anaesthesia (DTA) (n = 7), and dehorned with ketoprofen and treated Area and treatment interactive effect with topical anaesthesia (DKTA) (n = 7). Calves not sharing the same Mechanical stimulation of the cut skin edge area resulted in superscript within each treatment are considered statistically significant (P lower mean MNT than stimulation of the peri-wound tissue < 0.05). (2.01 vs 3.81 kg/f, respectively) (Fig. 3). Differences varied depending on treatment with the greatest difference seen in Discussion DTA calves (2.09 kg/f) and similar differences in D, DK and This study assessed the efficacy of a topical anaesthetic DKTA calves (1.63–1.7 kg/f; P = 0.02). formulation in combination with the NSAID ketoprofen, for Topical anaesthesia for dehorning in calves Animal Production Science E the pain amelioration of scoop dehorning wounds in calves. As et al. 1998a; Sutherland et al. 2002), or orally (Faulkner

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s Animal Production Science E the pain amelioration of scoop dehorning wounds in calves. As et al. 1998a; Sutherland et al. 2002), or orally (Faulkner and hypothesised, calves treated with TA were significantly less Weary 2000). In addition, local anaesthesia was administered pressure-sensitive than calves dehorned without TA (except at topically rather than via subcutaneous infiltration, allowing for 24 h post-treatment). Treatment with ketoprofen reduced slower absorption and concentration of the actives at the injury pressure sensitivity with significant reductions observed 1 and site. 2 h post-treatment. The combined use of TA and ketoprofen The effect of an NSAID on the pain sensitivity of disbudding resulted in some reduced pressure sensitivity compared with wounds has been previously investigated. Calves that were calves dehorned without analgesia, however no additive effect cautery disbudded following the administration of meloxicam was observed with DKTA calves displaying similar sensitivity and lignocaine (cornual nerve block), displayed lower pain to DTA calves. sensitivity (as determined through algomtery) 4 h after Previous research has shown that TA significantly reduces disbudding than calves given lignocaine alone (Heinrich et al. pain sensitivity for at least 1.5 h post-dehorning (Espinoza et al. 2010). This indicates the effectiveness of an NSAID as an 2013). However, as the pain of dehorning appears to be most ameliorant for acute dehorning pain. Results from the present severe during the 7–9 h post-procedural period, and may still be study also found significantly lower pain sensitivity in evident 1–2 days later, addressing chronic pain is considered ketoprofen-treated calves 1 and 2 h post-dehorning compared important (Sylvester et al.

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evident 1–2 days later, addressing chronic pain is considered ketoprofen-treated calves 1 and 2 h post-dehorning compared important (Sylvester et al. 1998, 2004a; Stafford and Mellor with calves not given ketoprofen. Another study, which 2005). Therefore, a combination of drugs, as used in the present investigated the effect of meloxicam on the pain sensitivity of study, may provide a multimodal approach to analgesia, which disbudding wounds, failed to detect any analgesic effect but has been demonstrated to be more efficacious (Coetzee 2011). attributed this finding to the probable inability of von Frey The post-operative application of TA on dehorning wounds monofilaments in exerting sufficient pressure to induce a resulted in significantly greater mean MNT than calves dehorned response (Mintline et al. 2013). Heinrich et al. (2010) and without TA. This reduced pain sensitivity in DTA and DKTA Mintline et al. (2013) studied meloxicam, believed to be a calves was observed for up to 5 h post-treatment, exceeding preferential cyclooxygenase-2 isoform inhibitor with a half-life the duration of efficacy of 1.5 h detected previously (Espinoza between 20 and 43 h. Ketoprofen is a nonspecific cyclooxygenase et al. 2013). This may be due to the increased concentration of inhibitor with a half-life in most animals of less than 2 h but bupivacaine in the current formulation (1% vs 0.5% in Espinoza duration of action up to 24 h (Papich 2010). The much shorter et al. 2013). The quantity of TA may also be important for half-life of ketoprofen compared with meloxicam may explain efficacy, with a larger volume used here than in previous work the seemingly diminishing effect from 1 to 2 h in the DK group. (7 mL vs 4 mL per dehorning wound). An important consideration Method

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in previous work the seemingly diminishing effect from 1 to 2 h in the DK group. (7 mL vs 4 mL per dehorning wound). An important consideration Method of dehorning is an important consideration given that however is the different modes of pain assessment used to gauge cautery (used in Heinrich et al. 2010; and Mintline et al. 2013) efficacy in the two experiments. The von Frey monofilaments and amputation dehorning (used in the present study) elicit used in Espinoza et al. (2013) were designed to bend at an even, very different wounds and subsequent pain responses. Cautery repeatable force (10 and 300 g/f). Thus the same force was exerted disbudding elicits first, second and third degree burns resulting on the wound and surrounding skin of all calves in order to invoke in the damage and destruction of nociceptors leading to altered or a pain response. This response to stimulation was then visually loss of sensation (Petrie et al. 1996). Thus cautery disbudding scored using a numerical rating scale ranging from 0 to 3 (no, has been suggested as less painful than amputation dehorning, minor, moderate or severe response). The present study utilised which results in a surgical wound resulting in bleeding, and algometry whereby tolerance (up to 10 kg/f) to increasing exposed and severed nociceptors. mechanical stimulation was measured and a quantitative The duration of nerve blockade provided by local anaesthetics outcome obtained. Therefore, the type of pain response being has been suggested as having an impact on the efficacy of measured is different between the two trials, which does not allow NSAID for the amelioration of dehorning pain (Stafford and for direct comparison. Mellor 2005). Ketoprofen in combination with lignocaine The administration of ketoprofen

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ration of dehorning pain (Stafford and for direct comparison. Mellor 2005). Ketoprofen in combination with lignocaine The administration of ketoprofen provided significant short- administered around the cornual nerve has been shown to term reduction in the pain sensitivity of dehorning wounds when virtually eliminate the cortisol response to dehorning, whereas compared with D calves (up to 2 h). However, no reduction was the use of bupivacaine appears to produce a delayed cortisol evident 5 and 24 h post-dehorning. The onset of ketoprofen has response once the bupivacaine wears off (McMeekan et al. been documented at 2 h post-dehorning (McMeekan et al. 1998a). While in this circumstance it is not clear why shorter- 1998a; Stafford and Mellor 2011) whereas other sources acting local anaesthesia is more effective than longer-acting local suggest a half-life in most animals of less than 2 h (Papich anaesthesia, this occurrence may explain why the ketoprofen and 2010). Hence the pharmacokinetics of ketoprofen are unclear. TA combination did not appear to have an enhanced analgesic DTA and DKTA calves exhibited similar mean MNT at all effect. time points following dehorning, whereas in other studies, the Important information is presented in the present study with combined use of ketoprofen and lignocaine has been shown to be respect to the onset of topical anaesthesia for dehorning wounds. effective at reducing the pain response to dehorning (McMeekan Evidence of local anaesthesia may be seen 1 min post-dehorning et al. 1998a; Faulkner and Weary 2000; Sutherland et al. 2002). and treatment with TA. Some indication of local anaesthesia Route of administration could account for these results. Although was seen in previous dehorning work at 1 min, though it was not the dose

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anaesthesia Route of administration could account for these results. Although was seen in previous dehorning work at 1 min, though it was not the dose is the same in the present study as in the literature (3 mg/ statistically significant when compared with control animals kg), ketoprofen was administered intramuscularly into the neck and could be due to the different tool used for assessment: von rather than intravenously into the calf jugular vein (McMeekan Frey monofilaments (Espinoza et al. 2013). Previous research F Animal Production Science C. A. Espinoza et al. on TA for castration and mulesing in lambs reported evidence for young calves undergoing scoop dehorning, as well as a of anaesthesia between 1 and 3 min post-treatment, respectively potential benefit for beef and dairy industries to address (Lomax et al. 2008, 2010). TA enables a faster onset of local welfare concerns with a relatively practical approach. anaesthesia than injectable administration, (which is 3–5 min All dehorned calves demonstrated increased sensitivity over for a cornual nerve block in calves) as agents are applied time. A limitation of this study is the inability to compare with directly to open wounds and mucosal surfaces allow rapid non-dehorned animals as no sham (positive control) animals absorption and action through exposed nerve endings and were included in the study. Rather, a reduction in pain from blood vessels. the dehorned animals (negative control) with a known painful The cut skin edge of the dehorning wound was found to be wound can be performed. It is likely that the decrease in MNT more sensitive than the peri-wound area, regardless of treatment. over time observed in all animals is due to tissue damage and the This supports previous findings of increased

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eri-wound area, regardless of treatment. over time observed in all animals is due to tissue damage and the This supports previous findings of increased sensitivity of the inflammatory process, and not an artefact of repeated testing. cut skin edge of mulesing wounds in lambs (Lomax et al. 2008). The pain following dehorning has been well documented (Petrie This sensitivity is likely to be caused by direct injury to et al. 1996; McMeekan et al. 1997, 1998b; Sylvester et al. nociceptors (Meyer et al. 2005). At the site of injury (the 2004b). Sham dehorned calves subjected to mechanical dehorning wound), sensitisation of exposed nerve endings stimulation with von Frey monofilaments did not display leads to an enhanced response from these nociceptors. increasing sensitivity but an unchanging response up to 24 and Production of inflammatory mediators and upregulation of 75 h post-sham dehorning (Espinoza et al. 2013; Mintline et al. proinflammatory enzymes, along with changes in tissue pH 2013). Whereas scoop dehorned calves showed an increased and electrolyte composition (Tapper 2011) can explain the sensitivity to von Frey stimulation up to 24 h post-dehorning significant decrease in mean MNT over time observed in the (Espinoza et al. 2013). Sham dehorned calves subjected to present study. There was a significant decrease in mean MNT pressure algometry showed a reduction in MNT over time over time indicating the effect of inflammatory mediators on (Tapper 2011) and this may be due to the return of sensation, exposed nerve endings in addition to uninjured tissue (Meyer or consequence, from the administration of two lignocaine et al. 2005). cornual nerve blocks given to all animals throughout the The TA formulation used previously and in this study, was experimental

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gnocaine et al. 2005). cornual nerve blocks given to all animals throughout the The TA formulation used previously and in this study, was experimental period. Repeated mechanical stimulation in modified from the original formulation designed for the sheep has produced mixed results. Healthy sheep with an mulesing of sheep in Australia (Tri-Solfen, Bayer Animal algometer strapped to their hind leg did not become sensitised Health, Pymble, NSW, Australia). Scoop dehorning wounds during the testing period (Nolan et al. 1987a, 1987b, 1987c; are usually significantly smaller than mulesing wounds Welsh and Nolan 1995). Another study using a handheld although there is often increased haemorrhage, particularly if algometer to determine the MNT of the forelimb of sheep arterial bleeding occurs (Espinoza et al. 2013). Aluminium observed a decrease in MNT over 3 days (Stubsjoen et al. chlorohydrate was included as a vasoconstrictive agent to 2010). The number of chosen time points may be an important promote haemostasis and slow the rate of systemic absorption consideration as each sheep was tested 30 times over a 30-min of anaesthetic actives, which aids in extending the duration of period. The inclusion of this group in future work would be local anaesthesia (Lomax et al. 2013). beneficial to compare sensitivity of intact and dehorned calves. There are several advantages to the post-operative application Pressure algometry is a novel indicator of the pain induced of local anaesthetics. In animal production, routine husbandry by dehorning despite its widespread use for the quantification procedures need to be performed quickly and efficiently due to of pain sensitivity for other bovine diseases (Dyer et al. 2007; time and labour constraints. TA can be applied easily, has a

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ly and efficiently due to of pain sensitivity for other bovine diseases (Dyer et al. 2007; time and labour constraints. TA can be applied easily, has a rapid Cutler et al. 2013; Fitzpatrick et al. 2013; Dewell et al. 2014). onset, and there is no need for double-handling of animals. Algometry is useful for the assessment of localised wound Post-operative application of TA allows direct contact of the pain and anaesthesia but does not quantify systemic analgesia. anaesthetic agents, lignocaine and bupivicaine, with damaged Algometry can be invasive as mechanical pressure is being used tissue and nerve endings. This direct contact between the source to measure hyperalgesia. The re-handling and restraint of of pain and the pain relieving actives improve efficacy and speed animals, which is required for pressure testing, can also cause of pain alleviation. Additionally, the haemostatic and antiseptic stress and potentially disturb the wound. agents are applied directly to the wound allowing pain, blood Algometry was chosen as the sole pain assessment tool in loss and infection to be treated simultaneously. Post-operative this study for several reasons. Algometry is a form of mechanical application of TA is therefore an effective, practical and cost- sensory testing, which induces a pain response in order to effective option for farmers, which minimises the amount of establish maximum nociceptive threshold. This induction of handling required (Lomax et al. 2010). pain would likely induce a cortisol response, thus interfering The high cost and impracticality of injectable pain relief with the measurement of cortisol. In addition, animals should methods have prevented the widespread uptake of pain relief be minimally handled for assessment of cortisol so that by the

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In addition, animals should methods have prevented the widespread uptake of pain relief be minimally handled for assessment of cortisol so that by the majority of cattle producers. Although a significant handling and restraint do not induce stress and a rise in amount of research has focussed on the use of injected local cortisol (Hemsworth et al. 2011). Behaviour assessment could anaesthesia for ameliorating dehorning pain (Morisse et al. not be combined with mechanical sensory testing as repeated- 1995; McMeekan et al. 1998a, 1999; Graf and Senn 1999; measures on each animal was being performed to document Sutherland et al. 2002; Stafford and Mellor 2005; Doherty changing sensitivity over time. This required animals to be re- et al. 2007; Stewart et al. 2009), this study is one of the first to handled and restrained at regular intervals, which would investigate the use of TA. TA has a potential welfare benefit disturb and confound any behaviour observations significantly. Topical anaesthesia for dehorning in calves Animal Production Science G To obtain quality data it is vital that behaviour observations be digital dermatitis in dairy cattle. Journal of Dairy Science 96, unobtrusive (Ploger and Yasukawa 2003), performed alone, and 7550–7557. doi:10.3168/jds.2012-6384 with minimal to no interference or handling for the observation Dewell RD, Millman ST, Gould SA, Tofflemire KL, Whitley RD, Parsons RL, period. Evaluation of TA and ketoprofen for dehorning pain could Rowe EW, Liu F, Wang C, O’Connor AM (2014) Evaluating approaches to measuring ocular pain in bovine calves with corneal scarification and be performed using physiological and behavioural indicators but infectious bovine keratoconjunctivitis-associated corneal ulcerations. in isolation and not in

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rmed using physiological and behavioural indicators but infectious bovine keratoconjunctivitis-associated corneal ulcerations. in isolation and not in conjunction with pressure algometry. Journal of Animal Science 92, 1161–1172. doi:10.2527/jas.2013-7264 Other limitations to the present study would require further Doherty T, Kattesh H, Adcock R, Welborn M, Saxton A, Morrow J, Dailey J examination. In future trials, the inclusion of a placebo gel would (2007) Effects of a concentrated lidocaine solution on the acute phase allow for effective blinding to treatment, in addition to evaluating stress response to dehorning in dairy calves. Journal of Dairy Science. a wound barrier effect that has previously been observed in 90, 4232–4239. doi:10.3168/jds.2007-0080 sheep (Lomax et al. 2008). Although the experiment was Duarte A, Pospisilova E, Reilly E, Mujenda F, Hamaya Y, Strichartz G conducted in an identical manner on both days of the study, (2005) Reduction of postincisional allodynia by subcutaneous future experiments should represent all treatments groups on bupivacaine – findings with a new model in the hairy skin of the rat. each day of the study. This would eliminate any potential Anesthesiology 103, 113–125. doi:10.1097/00000542-200507000- confounding by ‘day of experiment’. 00018 Through the use of pressure algometry, it can be concluded Dyer RM, Neerchal NK, Tasch U, Wu Y, Dyer P, Rajkondawar PG (2007) Objective determination of claw pain and its relationship to limb that TA is able to provide pain relief in under 3-month-old dairy locomotion score in dairy cattle. Journal of Dairy Science 90, calves for up to 5 h post-scoop dehorning. This was evident 4592–4602. doi:10.3168/jds.2007-0006 through reduced pressure sensitivity at both the cut skin

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es for up to 5 h post-scoop dehorning. This was evident 4592–4602. doi:10.3168/jds.2007-0006 through reduced pressure sensitivity at both the cut skin edge of Espinoza C, Lomax S, Windsor P (2013) The effect of a topical anesthetic the wound and the peri-wound area. A combined effect of TA and on the sensitivity of calf dehorning wounds. Journal of Dairy Science ketoprofen was not detected with the methods used and should be 96, 2894–2902. doi:10.3168/jds.2012-5954 further investigated. The low MNT observed 24 h after dehorning Faulkner P, Weary D (2000) Reducing pain after dehorning in dairy calves. suggests that dehorning causes prolonged pain. Extending the Journal of Dairy Science 83, 2037–2041. doi:10.3168/jds.S0022-0302 observation period beyond 24 h will help understand the (00)75084-3 generation and extent of pain following dehorning. TA offers a Fisher A, Paull D, Lee C, Atkinson S, Colditz I (2008) New research on pain- practical and effective option for improving the welfare of young alleviating methods for farm animals. In ‘Scientific assessment and calves undergoing scoop dehorning. management of animal pain’. (Eds D Mellor, P Thornber, D Bayvel, S Kahn) pp. 145–156. (World Organisation for Animal Health: Paris, Acknowledgements France) Fitzpatrick CE, Chapinal N, Petersson-Wolfe CS, DeVries TJ, Kelton DF, The authors gratefully acknowledge Kim McKean for provision of calves Duffield TF, Leslie KE (2013) The effect of meloxicam on pain and equipment, Bayer Animal Health for provision of topical anaesthetic sensitivity, rumination time, and clinical signs in dairy cows with and Mark Hazelton for practical assistance. The statistical advice of Peter endotoxin-induced clinical mastitis. Journal of Dairy Science 96, Thomson, Evelyn Hall and Mary

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practical assistance. The statistical advice of Peter endotoxin-induced clinical mastitis. Journal of Dairy Science 96, Thomson, Evelyn Hall and Mary Abdelsayed is greatly appreciated. 2847–2856. doi:10.3168/jds.2012-5855 Gottardo F, Nalon E, Contiero B, Normando S, Dalvit P, Cozzi G (2011) References The dehorning of dairy calves: practices and opinions of 639 farmers. Anonymous (1997) FAWC Report on the Welfare of Dairy Cattle. Available Journal of Dairy Science 94, 5724–5734. doi:10.3168/jds.2011-4443 at http://webarchive.nationalarchives.gov.uk/20121007104210/http:// Graf B, Senn M (1999) Behavioural and physiological responses of calves www.fawc.org.uk/reports/dairycow/dcowr069.htm [Verified 9 April to dehorning by heat cauterization with or without local anaesthesia. 2015] Appl. Anim. Behav. Sci. 62, 153–171. doi:10.1016/S0168-1591(98) Anonymous (2004a) Primary Industries Standing Committee Model Code 00218-4 of Practice for the Welfare of Animals: Cattle. Available at http://www. Guatteo R, Levionnois O, Fournier D, Guemene D, Latouche K, Leterrier C, publish.csiro.au/nid/22/pid/4831.htm [Verified 2 June 2013] Mormede P, Prunier A, Serviere J, Terlouw C, Neindre P (2012) Anonymous (2004b) Dehorning of cattle. Available at http://www.ava.com. Minimising pain in farm animals: the 3s approach – ‘suppress, au/policy/84-dehorning-cattle [Verified 2 June 2014] substitute, soothe. Animal 6, 1261–1274. doi:10.1017/S1751731112 Clark C, Mendl M, Jamieson J, Arnone A, Waterman-Pearson A, Murrell J 000262 (2011) Do psychological and physiological stressors alter the acute pain Heinrich A, Duffield T, Lissemore K, Millman S (2010) The effect of response to castration and tail docking in lambs? Veterinary Anaesthesia meloxicam on behavior and pain sensitivity

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