Topical anesthesia mitigates the pain of castration in beef calves

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Topical anesthesia mitigates the pain of castration in beef calves S. Lomax and P. A. Windsor J ANIM SCI 2013, 91:4945-4952. doi: 10.2527/jas.2012-5984 originally published online August 21, 2013 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.journalofanimalscience.org/content/91/10/4945 www.asas.org Downloaded from www.journalofanimalscience.org at University of Sydney Library on September 29, 2013 References This article cites 31 articles, 6 of which you can access for free at: http://www.journalofanimalscience.org/content/91/10/4945#BIBL Downloaded from www.journalofanimalscience.org at University of Sydney Library on September 29, 2013 Topical anesthesia mitigates the pain of castration in beef calves1 S. Lomax2 and P. A. Windsor Faculty of Veterinary Science, University of Sydney, PMB 3, Camden, NSW 2570, Australia ABSTRACT: Castration involves the removal of the was measured as maximum pressure (g) exerted by the testes and is performed to improve product quality and electronic anesthesiometer to invoke animal reflex, and management of male calves. The procedure has been responses to the von Frey monofilaments were scored proven to cause significant pain and stress, and despite from 0 to 3 using a NRS on the basis of local and central several attempts to reduce the impact of castration on motor reflexes. Calves treated with TA displayed sig- animal welfare, there has yet to be a practical and afford- nificantly less pain-related behaviors up to 3.5 h after able option made available for farmer application. To castration than untreated calves (P < 0.001) and did not address this issue, we conducted 2 trials (n = 18 and differ from uncastrated controls. Topical anesthetic– 27) to

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ated calves (P < 0.001) and did not address this issue, we conducted 2 trials (n = 18 and differ from uncastrated controls. Topical anesthetic– 27) to examine the efficacy of topical anesthetic Tri- treated calves also exhibited significantly greater pain Solfen (TA) to alleviate the pain of surgical castration. threshold of the wound (559.2 ± 14.3 g) and surrounding Angus bull calves (135.8 ± 5.7 kg) aged 3 to 4 mo were skin (602.8 ± 16.5 g) than untreated calves (446.0 ± 18.9 randomly allocated to 3 treatment groups, including and 515.3 ± 20.4 g, respectively; P < 0.001). Control surgical castration, castration in combination with TA, and TA-treated calves had significantly lower mean and uncastrated controls. In Trial 1, pain-related behav- response scores to von Frey stimulation than untreated ior was assessed using a customized numerical rating calves (0.333, 0.978, and 4.289, respectively; P < 0.001). scale (NRS) over 4 h. In Trial 2, pre- and postoperative Results indicate that TA effects rapid and prolonged pain skin sensitivity of the wound and periwound areas was alleviation in calves up to 24 h after castration. Topical assessed using an electronic von Frey anesthesiometer anesthesia may present a cost-effective, practical, on- (IITC Life Sciences, Woodland Hills, CA) and von Frey farm approach to pain alleviation and is proposed as monofilaments (300 g). Sampling was repeated at 1 min a potential tool for reducing the welfare impact on the and 2, 4, 6, and 24 h after castration. Pain threshold beef animal in routine husbandry procedures. Key words: castration, electronic anesthesiometer, numerical rating scale, pain threshold, topical anesthesia, von Frey monofilaments © 2013 American Society of Animal Science. All rights reserved. J. Anim. Sci.

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rating scale, pain threshold, topical anesthesia, von Frey monofilaments © 2013 American Society of Animal Science. All rights reserved. J. Anim. Sci. 2013.91:4945–4952 doi:10.2527/jas2012-5984 INTRODUCTION tion has been well documented as painful (Molony et al., 1995; Fisher et al., 1996) but is considered nec- Castration of male calves is a routine husbandry essary for economic, safety, and management reasons. procedure commonly performed without anesthesia There has been significant research into the use of local or analgesia in cattle herds around the world. Castra- anesthesia and various analgesics to address the pain associated with castration (Fisher et al., 1996; Earley 1The financial support of the Australian Research Council, and Crowe, 2002; Stilwell et al., 2008; Coetzee, 2011). Bayer Animal Health Australia, and Animal Ethics Pty Ltd is grate- Although these options are effective, they fail to pro- fully acknowledged. The authors thank Steve Burgun and his staff at vide farmers with a practical and affordable option Arthursleigh, Marulan, NSW, and honors student Rachel Wilson from for incorporation into farm management. Huxley and the University of Sydney for their logistical support. We are grateful for the statistical advice from Peter Thomson from the University Whay (2007) reported that for the majority of produc- of Sydney. ers, the cost of analgesic agents was a significant issue 2Corresponding author: sabrina.lomax@sydney.edu.au deterring them from adopting such practices. Growing Received October 14, 2012. Accepted June 27, 2013. public concern about farm animal welfare makes it in- 4945 4946 Lomax and Windsor creasingly important to find more ethical and welfare- tunica was made from the base of the scrotum anteri- appropriate methods of

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6 Lomax and Windsor creasingly important to find more ethical and welfare- tunica was made from the base of the scrotum anteri- appropriate methods of conducting routine husbandry orly (approximately 2.5 cm) to expose the testes. Each procedures. Incorporation of practical and affordable testicle was pushed through the opening in the scrotum, methods of pain relief into routine surgical procedures and the surrounding tunica was removed. The exposed on farms is important for improving on-farm welfare. spermatic cord was then severed with the knife approxi- Tri-Solfen (Bayer Animal Health, Pymble NSW, mately 12 cm proximal to the head of the epididymis. Australia) is a commercially available topical anesthetic In groups receiving TA treatment, Tri-Solfen was ap- (TA), hemostatic, and antiseptic agent for the allevia- plied to each of the exposed spermatic cords proximal tion of mulesing pain in sheep. It consists of lignocaine to the site of incision, before the removal of the testis, (40.6 g/L), bupivacaine (4.5 g/L), adrenalin (24.8 mg/L), by inserting the nozzle of the applicator (N.J. Phillips and cetrimide (5.0 g/L) in a gel base. It has been re- Australia F-grip 2-mL injector, Gosford NSW, Australia) ported that Tri-Solfen is effective in alleviating pain of along the length of each cord as far into the scrotum as mulesing, castration, and tail docking in sheep and im- possible. Three milliliters of TA were applied liberally to proves wound healing (Lomax et al., 2008, 2010, 2013). coat each spermatic cord and to ensure maximal cover- Because of the efficacy of this TA for reducing surgi- age of the retracting tissue. An additional 2 to 3 mL of cal pain in lambs and the similar anatomical nature of TA was applied to the cut edge of the scrotal wounds the wounds, we

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An additional 2 to 3 mL of cal pain in lambs and the similar anatomical nature of TA was applied to the cut edge of the scrotal wounds the wounds, we hypothesized that a comparable effect after the procedure. Because of the blue staining caused would be seen in calves. Thus, this research examines by Tri-Solfen, the wounds of castrated calves not treated the efficacy of TA for reducing the pain of castration with Tri-Solfen and the scrotum of control calves were wounds in beef calves. painted with blue food dye to blind observers to treat- ment in both trials. MATERIALS AND METHODS Application method is pivotal to maximum efficacy of the topical anesthetic in these trials. Insertion of the ap- All animal procedures were conducted with prior in- plicator into the scrotal sac and spraying into the vicinity stitutional animal ethics approval in accordance with the of the external inguinal ring ensured that the formulation National Health and Medical Research Council Code of pooled against the mucosal surfaces for fast and efficient Practice for the Care and Use of Animals for Scientific absorption. In addition, once the extracted spermatic cord Purposes. was severed, the retracting cord and exposed nerve end- ings were bathed in a pool of anesthetic formulation, en- Husbandry of Calves abling almost immediate absorption and anesthesia. Two trials were conducted using Angus bull calves Trial 1: Assessment of Acute Pain-Related Behavior selected from a commercial herd in the Central Table- lands of New South Wales, Australia. Calves were 3 to 4 Behavior was assessed over the first 4 h after cas- mo of age, born in the winter of 2008, with a mean initial tration to examine any acute effects of wound pain or BW of 135.8 ± 5.7 kg. Calves were randomly allocated anesthesia on

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of 2008, with a mean initial tration to examine any acute effects of wound pain or BW of 135.8 ± 5.7 kg. Calves were randomly allocated anesthesia on calf recovery, as comparable to previous to 1 of 3 treatment groups to compare calf responses results in lambs (Lomax et al., 2010). Eighteen calves with surgical castration with and without TA treatment were weighed and randomly assigned to 1 of the 3 treat- to those of uncastrated controls. Control calves were ment groups as described above. Calves were individu- handled in the same manner as castrated calves, where ally identified by numbers 1 through 18 with colored the scrotal sac was physically manipulated without spray marker on their sides and back to assist behavioral surgery. On the day of each experiment, calves were observations. They were then handled and treated ac- separated from their mothers into a holding yard and cordingly before being released into a large observation weighed, ear-tagged and ear-notched, vaccinated, and yard (50 m2). The holding yard had complete ground placed in a calf cradle for treatment. The cradle used in cover, and calves had access to their mothers to allow these experiments was a swing-away squeeze chute that them to express natural feeding and other behaviors. could be turned on its side to place the animal in lateral Pain-related behavior assessments were performed by a recumbency for the performing of procedures. trained observer, blind to treatment group strategy at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, and 4 h after castration. Method of Surgical Castration and Topical Pain-related behavior was assessed using a previ- Anesthetic Application ously developed, customized numerical rating scale (NRS; Lomax et al., 2008, 2010). Individual calves Surgical castration was performed using

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lication ously developed, customized numerical rating scale (NRS; Lomax et al., 2008, 2010). Individual calves Surgical castration was performed using a steril- were allocated a score between 0 and 3 based on be- ized scalpel. An incision through the skin and testicular havioral indicators of pain, where 0 = no pain-related Topical anesthesia and castration 4947 behavior, indicated by liberal feeding and suckling and no signs of abnormalities of gait and posture; 1 = mild abnormalities of posture, gait, or behavior, such as mild kyphosis without hyperextension of hind legs, ventral recumbency with hind legs partially extended, or mild stiffening of gait without overt limping or leg dragging; 2 = moderate abnormalities of posture, gait, or behavior, such as “statue standing” with head down and promi- nent kyphosis, moderate stiffening or slowing of gait, hyperextension and abduction of hind legs, or ventral recumbency with legs fully extended; 3 = display of severe abnormalities of posture, gait, or behavior, such as marked agitation with twisting or writhing, high fre- quency of postural change from lying to kneeling or standing, distressed vocalization, and lateral or prostrate Figure 1. Electronic anesthesiometer applied to castration wound. lying, kneeling, or shaking. Trial 2: Assessment of Skin and Wound Sensitivity rump and head and were graded by severity of expres- sion using a NRS. Response scores were graded as 0 Twenty-seven calves were used in this trial to assess = no response; 1 = minor involuntary motor responses skin and wound sensitivity postcastration. Quantitative such as minor facial “awareness,” such as eye widening sensory testing of the wound and surrounding skin was or blinking or nasal flaring, local skin twitch, subcutane- used to

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eness,” such as eye widening sensory testing of the wound and surrounding skin was or blinking or nasal flaring, local skin twitch, subcutane- used to assess sensitivity over the initial expected action ous muscle twitch, or anal contraction; 2 = partial head period of the TA (4 to 6 h) and at 24 h to assess extended or rump withdrawal reflex, such as slight lifting of the efficacy of the actives beyond the product description. snout or partial head rotation, multiple subcutaneous This was measured by means of a pressure transducer muscle group contraction, and lifting of the tail; 3 = full (electronic von Frey anesthesiometer with rigid tips; 0 startle reflex of the head, resulting in a major movement, to 1,000 g; IITC-Life Science Instruments, Woodland such as lifting head off the cradle, full head jerk or full Hills, CA) and through the use of a von Frey monofila- head rotation, or full rump withdrawal reflex with lifting ment (300 g, Bailey Instruments Ltd., Manchester, UK). of the rump off the cradle. Total scores were calculated Calves were restrained in the calf cradle, and testing was out of 6 for periwound sensitivity and out of 12 for di- performed before castration and at 3 min and 2, 6, and rect wound sensitivity. 24 h after castration. Electronic von Frey Anesthesiometer. Animals Statistical Analysis were placed in the calf cradle, and the tip of the anes- thesiometer was applied to the wound and surrounding Data were analyzed using Genstat software (VSN (periwound) skin (Fig. 1). Pain threshold was automati- International, hemel Hempstead, UK). Residual maxi- cally recorded as maximum pressure (g) exerted before mum likelihood estimation linear mixed model analy- animal motor response and withdrawal from the device. ses were used to analyze differences

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before mum likelihood estimation linear mixed model analy- animal motor response and withdrawal from the device. ses were used to analyze differences between treatment von Frey Monofilament. Von Frey monofilaments groups for all behavioral and wound sensitivity testing are calibrated to bend at a predetermined pressure to data, with the factors time, treatment, and interaction be- provide repeatable pain stimulation of predetermined tween time and treatment as explanatory variables and sites on the wound and surrounding (periwound) skin, calf number as the random effect. Where a significant as previously described in lambs (Lomax et al., 2008, interaction was found, post hoc pairwise comparisons 2010). A 300-g filament was used to perform direct sen- using LSD were performed to analyze between-group sory testing at 4 predetermined sites on the cut skin edge differences (Table 1). For all statistical calculations, P < of the scrotal wound and 2 sites on the intact skin sur- 0.05 was considered statistically significant. rounding the wound. Evidence of local anesthesia (diminished response RESULTS to tactile stimulation) and primary and secondary hy- peralgesia (heightened response to stimulus directly in Pain-Related Behavior the damaged tissue or in surrounding undamaged tis- sue, respectively) were assessed at each site. Responses There was a significant treatment effect on pain- were scored by monitoring induced motor reflexes in the related behavior (Table 2). Calves treated with TA ex- 4948 Lomax and Windsor Table 1. Statistical interactions and df tested in Trials 1 Response scores in the TA-treated calves were sig- and 2 nificantly below those of the untreated calves between 2 Response Wald and 24 h after castration (P < 0.001; Table 4). Response Trial variate

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g- and 2 nificantly below those of the untreated calves between 2 Response Wald and 24 h after castration (P < 0.001; Table 4). Response Trial variate Factor statistic n.df2 P-value scores to stimulation of the skin surrounding the castra- Trial 1 Behavior Interaction1 23.85 14 0.001 tion wound were significantly lower in TA-treated calves Trial 2 than in untreated calves at 2 and 6 h after castration. E lectronic anesthesiometer Wound Interaction1 34.68 8 0.001 Response scores to stimulation of the wound and Periwound Interaction1 16.17 8 0.001 surrounding skin of TA-treated calves did not differ sig- V on Frey nificantly from uncastrated controls between 1 min and monofilament 6 h after castration but were significantly greater by 24 Wound Interaction1 93.2 8 0.001 h (P < 0.001). Periwound Interaction1 54.15 8 0.001 1Time × treatment. DISCUSSION 2Number of degrees of freedom for sample size n. There are increasing economical and ethical impera- tives to address pain associated with routine husbandry pressed significantly less pain than untreated calves at procedures, such as castration of beef calves. Local an- all time points after castration (P < 0.001). esthetics, such as lignocaine, have been found to reduce acute pain associated with castration when injected into Electronic von Frey Anesthesiometer the neck of the scrotum and into the spermatic cord (Fisher et al., 1996; Stafford et al., 2002; U.S. National Before castration, there was no significant dif- Library of Medicine, 2010a). Regardless, local anes- ference in the pain threshold between the 3 treatment thetic injections are rarely incorporated into routine hus- groups, with mean pressures of 605.4 ± 17.5 g exerted bandry procedures of commercial cattle properties. on the preincision wound site and

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outine hus- groups, with mean pressures of 605.4 ± 17.5 g exerted bandry procedures of commercial cattle properties. on the preincision wound site and 628.4 ± 18.3 g on the The development of an affordable and practical skin surrounding the wound site. means of pain alleviation for such procedures is pro- There was a significant effect of treatment (P < 0.001) posed for incorporation into routine farm management and time (P < 0.001) on pain threshold after castration. practices. Topical anesthesia, applied during and imme- Predicted grand means for treatment showed that control diately after the procedure, has previously been found calves had the greatest pressure threshold of the wound to be practical and effective for reducing postoperative (613.0 ± 12.2 g) and surrounding skin (637.0 ± 16.7 g), pain associated with surgical husbandry procedures in followed by TA-treated castrated calves (559.2 ± 14.3 sheep (Paull et al., 2007; Lomax et al., 2008, 2010; U.S. and 602.8 ± 16.5 g), with untreated castrated calves hav- National Library of Medicine, 2010b). Our studies pres- ing the most sensitivity (446.0 ± 18.9 and 515.3 ± 20.4 ent evidence that amelioration of pain up to 24 h can be g). Uncastrated control calves had the greatest wound achieved for calves undergoing surgical castration us- pain thresholds at all time points after castration (Table ing a farmer-applied, spray-on topical anesthetic. These 3). The TA-treated calves exhibited significantly greater findings have major welfare implications for all live- wound pain thresholds than untreated castrated calves at stock undergoing such procedures. all time points after castration. Local anesthetic agents act directly on nerve tissue Untreated calves also had significantly lower peri- to inhibit the

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time points after castration. Local anesthetic agents act directly on nerve tissue Untreated calves also had significantly lower peri- to inhibit the conduction of nerve impulses responsible wound pain threshold values than both TA-treated and for the sensation of pain. They are absorbed through mu- control calves between 2 and 6 h after castration. Peri- cosal surfaces and damaged skin and can effect rapid and wound pain thresholds did not differ significantly be- profound local anesthesia when applied to open wounds tween treated and control calves. (Brofeldt et al., 1989; Jellish et al., 1999; Kokinsky et al., 1999; Lomax et al., 2008, 2010). Substance P and bra- von Frey monofilament dykinin are chemical mediators involved in the inflam- matory response which cause vasodilation, edema, and There was minimal response to pain stimulation of the release of histamine (Ren and Dubner, 1999; U.S. the wound site and surrounding skin before castration. National Library of Medicine, 2010b). They can have a Mean NRS response to testing was 0.55 ± 0.2 for the slow and prolonged effect, leading to increased sensiti- wound site (maximum possible score of 12) and 0.19 ± zation of neurons to nociceptive signals and exacerbated 0.09 for the surrounding skin (maximum possible score pain to noxious stimuli. Local anesthetics have been of 6). There were no significant differences between found to suppress bradykinin and substance P-mediated groups (Table 4). signaling (U.S. National Library of Medicine, 2010b). Topical anesthesia and castration 4949 Table 2. Mean pain-related behavior numerical rating scale score (±SE) and pairwise comparisons of differences between treatment means at various time points after castration comparing untreated castrated calves with castrated calves

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comparisons of differences between treatment means at various time points after castration comparing untreated castrated calves with castrated calves treated with topical anesthetic (TA) and uncastrated controls Treatment means Mean differences Time,1 h Control Treated2 Untreated Control − Treated Control − Untreated Treated − Untreated 0.5 0.00 0.17 ± 0.16 0.50 ± 0.22 -0.17 -0.503 -0.333 1 0.00 0.67 ± 0.33 1.17 ± 0.31 -0.673 -1.173 -0.503 1.5 0.00 0.33 ± 0.21 1.50 ± 0.22 -0.333 -1.503 -1.173 2 0.00 0.00 1.33 ± 0.33 0.00 -1.333 -1.333 2.5 0.33 ± 0.21 0.00 1.17 ± 0.31 0.333 -0.833 -1.173 3 0.00 0.17 ± 0.17 1.33 ± 0.33 -0.17 -1.333 -1.173 3.5 0.17 ± 0 0.00 1.17 ± 0.17 0.17 -1.003 -1.173 4 0.33 ± 0.21 0.33 ± 0.21 0.83 ± 0.17 0.00 -0.503 -0.503 1Time after castration. 2Treatment with 6mL Tri-Solfen (Bayer Animal Health, Pymble, Australia). 3P < 0.001, based on LSD of 0.205. The result is the attenuation of cutaneous microvascu- et al., 2008). This also supports previous observations of lar flare responses in damaged tissue and reduced in- absent or significantly reduced pain-related behaviors in flammation and therefore decreased hyperalgesia of the lambs treated with TA applied into the castration and tail wound and surrounding skin. docking wounds (Lomax et al., 2010). Local anesthesia via injection of lidocaine and bupi- In Trial 2, results from mechanical stimulation of vacaine has been shown to significantly reduce the cor- the castration wound and surrounding skin with both tisol response to surgical castration (Earley and Crowe, von Frey monofilaments and the electronic anesthesi- 2002; Stafford et al., 2002; Coetzee, 2011). Our results ometer indicated that significant wound anesthesia was indicate that topical anesthesia can effect a similar

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et al., 2002; Coetzee, 2011). Our results ometer indicated that significant wound anesthesia was indicate that topical anesthesia can effect a similar reduc- achieved within 1 min of castration. These results con- tion in pain. Trial 1 showed that calves castrated without cur with previous findings in lambs undergoing surgi- topical anesthetic treatment displayed more pain-related cal husbandry procedures (Lomax et al., 2008, 2010). behaviors, including stiffness of gait, hunched postures, Calves that received TA were found to tolerate greater prostration, and less feeding, than treated and uncastrated pressure exertion on the wound and periwound surfaces control calves. These findings are consistent with behav- after castration. The same calves had significantly lower ioral observations of calves receiving local anesthetic NRS responses to pain stimulation of the wound and infiltration of the spermatic cord and scrotum (Boesch Table 3. Mean pressure (g) exerted on wound and periwound surfaces (±SE) and pairwise comparisons of differences between treatment means at various time points after castration comparing untreated castrated calves with castrated calves treated with topical anesthetic (TA) and uncastrated controls Treatment Mean differences Time1 Control Treated2 Untreated Control − Treated Control − Untreated Treated − Untreated Wound Precastration 577.3 ± 19.8 641.7 ± 39.5 597.2 ± 27.9 -64.4 -19.9 44.5 1 min 616.4 ± 44.9 555.8 ± 22.6 449.3 ± 30.8 60.6 167.13 106.53 2h 585.2 ± 20.6 523.5 ± 8.2 426.3 ± 24.5 61.7 158.93 97.23 6h 644 ± 15.5 537.2 ± 22.1 330.8 ± 21.5 106.83 313.23 206.43 24 h 641.8 ± 22.7 537.9 ± 42.9 426.5 ± 48.8 103.93 215.33 111.43 Periwound Precastration 624.3 ± 30.4 651.9 ± 39.1 609.1 ± 26.5 -27.6 15.2 42.8 1 min 567.6

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641.8 ± 22.7 537.9 ± 42.9 426.5 ± 48.8 103.93 215.33 111.43 Periwound Precastration 624.3 ± 30.4 651.9 ± 39.1 609.1 ± 26.5 -27.6 15.2 42.8 1 min 567.6 ± 20.6 538.4 ± 32.1 513.2 ± 27.7 29.2 54.4 25.2 2h 691.4 ± 47.1 583.7 ± 18.9 462.4 ± 49.7 107.74 2294 121.34 6h 596.5 ± 25.1 630.9 ± 32 431.0 ± 59.1 -34.4 165.54 199.94 24 h 705.1 ± 41.1 609.2 ± 51.1 560.6 ± 36.8 95.9 144.54 48.6 1Time after castration. 2Treatment with 6mL Tri-Solfen (Bayer Animal Health, Pymble, Australia). 3P < 0.001, based on LSD of 84.02. 4P = 0.049, based on LSD of 106.5. 4950 Lomax and Windsor Table 4. Mean numerical rating scale score (±SE) and pairwise comparisons of differences between response to pain stimulation of the castration wound and surrounding skin with a 300-g von Frey filament at various time points after castration comparing untreated castrated calves with castrated calves treated with topical anesthetic (TA) and uncastrated controls Treatment Mean differences Time1 Control Treated2 Untreated Control − Treated Control − Untreated Treated − Untreated Wound Precastration 0.67 ± 0.44 0.56 ± 0.38 0.44 ± 0.24 0.11 0.22 0.11 1 min 0.44 ± 0.29 0.44 ± 0.24 1.67 ± 0.53 0.00 -1.22 -1.22 2h 0.22 ± 0.15 0.22 ± 0.15 6.22 ± 0.86 0.00 -6.003 -6.003 6h 0.11 ± 0.11 1.11 ± 0.42 7.11 ± 0.98 -1.00 -7.003 -6.003 24 h 0.22 ± 0.15 2.56 ± 0.85 6.00 ± 0.78 -2.333 -5.783 -3.443 Periwound Precastration 0.11 ± 0.11 0.33 ± 0.24 0.11 ± 0.11 -0.22 0.00 0.22 1 min 0.22 ± 0.22 0.11 ± 0.11 0.67 ± 0.37 0.11 -0.44 -0.56 2h 0.22 ± 0.22 0.00 ± 0 2.44 ± 0.29 0.22 -2.224 -2.444 6h 0.00 ± 0 0.11 ± 0.11 1.89 ± 0.39 -0.11 -1.894 -1.784 24 h 0.11 ± 0.11 0.56 ± 0.24 1.11 ± 0.35 -0.44 -1.004 -0.56 1Time after castration. 2Treatment with 6mL Tri-Solfen (Bayer Animal Health,

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-1.894 -1.784 24 h 0.11 ± 0.11 0.56 ± 0.24 1.11 ± 0.35 -0.44 -1.004 -0.56 1Time after castration. 2Treatment with 6mL Tri-Solfen (Bayer Animal Health, Pymble, Australia). 3P < 0.001, based on LSD of 1.41. 4P < 0.001, based on LSD of 0.64. thus were concluded to have less wound and periwound tivity. To obtain more objective, discrete data, we also pain than untreated calves. used electronic anesthesiometry. The results from both In this study we elected to combine behavioral ob- forms of quantitative sensory testing appeared to align servations with 2 methods of quantitative sensory test- well, showing similar levels of significance in the dif- ing to clinically assess the pain responses to surgery. We ferences between treatment groups. Correlation tests to examined pain-related behavior using a numerical rating validate this observation are proposed, as the 2 meth- scale, a method commonly used for grading behavior ods have different ways of eliciting pain response. The (Mathews, 2000; Anil et al., 2002, 2005; Hartrick et al., von Frey monofilaments are a sudden, acute stimula- 2003). Subjectivity was minimized through the use of a tion of the wound site to elicit a behavioral response, single trained observer, blinded to treatment protocol. which is graded on vigor. The electronic anesthesiom- Quantitative sensory testing is a widely used, vali- eter provides slow increasing pressure to elicit animal dated technique that we have previously used in lambs withdrawal from the noxious stimuli, at which point the to record the onset, evolution, and distribution of pain maximum pressure exerted may exceed that of the sud- from mulesing and castration wounds and their response den stimulus from the monofilament. to topical local anesthetic (Lomax et al., 2008, 2010). It

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from mulesing and castration wounds and their response den stimulus from the monofilament. to topical local anesthetic (Lomax et al., 2008, 2010). It There was evidence of a significant and persistent is an objective, repeatable form of pain assessment en- reduction in primary and secondary hyperalgesia 24 h abling the assessor to distinguish between various anal- after castration in calves treated with TA. Extended ef- gesic interventions (Duarte et al., 2005). Hypersensitivity ficacy of the topical anesthetic is attributed to the inclu- (hyperalgesia and allodynia) induced by inflammation or sion of adrenaline in the formulation. When used topi- nerve injury has been extensively studied as an indicator cally, adrenaline acts as a vasoconstrictor, slowing the of perioperative and postoperative pain in humans and rate of systemic absorption of the 2 anesthetic agents in animals (Bose, 1979; Wall, 1984; Malatinsky et al., 1986; the formulation and reducing wound hemorrhage. This Kawamata et al., 2002; Brower and Johnson, 2003). reduced rate of systemic absorption is likely to prolong We examined wound hypersensitivity using 2 forms the presence of the anesthetic agents concentrated at of quantitative sensory testing. Von Frey monofilaments the wound site and slows the metabolism of the agents, are commonly used in human and animal medicine, and thereby prolonging the intensity and duration of the lo- we have used them in previous ovine studies to assess cal anesthesia. In addition, the vasoconstrictive proper- hyperalgesia, allodynia (hypersensitivity to normally ties of adrenaline slow blood flow to the wound, thereby nonnoxious stimuli), and hypoesthesia (Lomax et al., suppressing the inflammatory cascade. The nerve end- 2008, 2010). Responses are recorded using a

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nonnoxious stimuli), and hypoesthesia (Lomax et al., suppressing the inflammatory cascade. The nerve end- 2008, 2010). Responses are recorded using a numerical ings in the damaged tissue are not exposed to inflamma- rating scale, despite concerns of subjectivity and sensi- Topical anesthesia and castration 4951 tory mediators that would cause them to become sensi- production animals, with product cost in addition to the tized, leading to decreased hyperalgesia. cost of employment of a veterinarian being significant Results from both techniques of sensory testing indi- barriers to general uptake (Stafford et al., 2005; Huxley cated no significant difference in secondary hyperalgesia and Whay, 2006). Options for analgesia are unlikely to of the periwound surface between treated and untreated be used in routine management procedures if their use calves 1 min after castration. Secondary hyperalgesia is is too time-consuming, costly, and generally impractical hypersensitivity in tissue adjacent to the wound and is for the farmer. It is likely that the use of analgesics may a consequence of central sensitization. This occurs as a become standard farm practice because of the falling result of peripheral sensitization (primary hyperalgesia) cost of most commonly used NSAID as more generic enhancing the pain responses of nociceptive neurons products become registered and available. However, in in the central nervous system (Ren and Dubner, 1999). the interim it is important to consider methods for effec- Dorsal horn neurons respond to peripheral inputs from tive and affordable alleviation of pain. the wound site and release chemical mediators that in- The topical anesthetic formulation examined in this crease central sensitization and lead to the perception of study has great

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ical mediators that in- The topical anesthetic formulation examined in this crease central sensitization and lead to the perception of study has great potential to improve the welfare of live- postoperative pain (Ren and Dubner, 1999; U.S. Nation- stock undergoing surgical castration. This method of al Library of Medicine, 2010b). This process tends to be delivery is desirable as it provides an option for safe, slower than peripheral sensitization, which explains why efficient, and effective anesthesia of castration wounds. there is very little secondary hyperalgesia seen within 1 Administering the product topically during and immedi- min of castration, whereas primary hyperalgesia appears ately postprocedure allows for rapid onset of anesthesia to develop immediately in untreated calves. In addition, (within 1 min on the basis of sensory testing results). the slow progression of the inflammatory cascade means This removes the need for double handling and has a there would be minimal vasodilation within 1 min in minimal time impact on regular farm operation. In ad- surrounding tissues, and thus, hypersensitivity would dition, the product is provided at a relatively low cost not yet have developed. (approximately AU$1 per head) through veterinarians. Despite the proven efficacy of various nonsteroidal anti-inflammatory drugs (NSAID) and local anesthetics Conclusions as discussed in the extensive reviews of Coetzee (2011) and Stafford et al. (2005, 2006), there is limited use of Through the combination of behavioral observa- these products by farmers and practitioners. Tradition- tions and quantitative sensory testing we conclude that ally, pain in farm animals has been overlooked because the topical anesthetic, antiseptic, and hemostatic formu- of attitudes of farmers

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conclude that ally, pain in farm animals has been overlooked because the topical anesthetic, antiseptic, and hemostatic formu- of attitudes of farmers and veterinary practitioners, prac- lation (Tri-Solfen) effects rapid and prolonged pain al- ticality, and economic constraints (Heleski et al., 2004; leviation in calves up to 24 h after castration. This was Huxley and Whay, 2006, 2007; Coetzee, 2011). There evident through a reduction in pain-related behaviors is a need to further assess these attitudes to pain and the and reduced sensitivity of the wound and surrounding use of analgesics in production animals. surfaces in treated calves. Although initially developed Limitations to the use of injectable anesthetics and for mulesing wounds, this type of product has the capac- NSAID arise from the delayed onset of action, the need ity to significantly reduce the acute pain associated with for veterinary administration, and the cost of the prod- routine husbandry procedures in livestock. ucts. Depending on the country, most drugs can only be obtained with a prescription by a veterinarian, and some LITERATURE CITED must be administered under veterinary supervision or Anil, L., S. Anil, and J. Deen. 2005. Pain detection and amelioration by a veterinarian (Sutherland et al., 1999). Furthermore, in animals on the farm: Issues and options. J. Appl. Anim. Welf. many of these anesthetics are invasive, requiring injec- Sci. 8:261–278. tion to the animal, and, depending on the drug, may take Anil, S., L. Anil, and J. Deen. 2002. Challenges of pain assessment in a matter of minutes to exert its effect (Coetzee, 2011). domestic animals. J. Am. Vet. Med. Assoc. 220:313–318. Boesch, D., A. Steiner, L. Gygax, and M. Stauffacher. 2008. Burdiz- This can require double handling of

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animals. J. Am. Vet. Med. Assoc. 220:313–318. Boesch, D., A. Steiner, L. Gygax, and M. Stauffacher. 2008. Burdiz- This can require double handling of animals and a time zo castration of calves less than 1-week old with and without delay between administration and procedure, both of local anaesthesia: Short-term behavioural responses and plasma which are impractical in large commercial operations. As cortisol levels. Appl. Anim. Behav. Sci. 114:330–345. with any substance that must be artificially introduced Bose, B. 1979. Burn wound dressing with human amniotic mem- into the body, there are various problematic side effects brane. Ann. R. Coll. Surg. Engl. 61:444–447. Brofeldt, B., P. Cornwell, D. Doherty, K. Batra, and R. Gunther. 1989. attributed to their use. Occupational health and safety Topical lidocaine in the treatment of partial-thickness burns. J. issues associated with the use of needles and scheduled Burn Care Rehabil. 10:63–68. drugs increase risk to producers and limit access. Finally, there are economic constraints to the use of analgesics in 4952 Lomax and Windsor Brower, M. C., and M. E. Johnson. 2003. Adverse effects of local an- Lomax, S., M. Sheil, and P. A. Windsor. 2013. Duration of action esthetic infiltration on wound healing. Reg. Anesth. Pain Med. of a topical anaesthetic formulation for pain management of 28:233–240. mulesing in sheep. Aust. Vet. J. 91:160–167. Coetzee, J. F. 2011. A review of pain assessment techniques and Malatinsky, J., M. Vigas, J. Jurcovicova, D. Jezova, S. Garayova, and pharmacological approaches to pain relief after bovine cas- M. Minarikova. 1986. The patterns of endocrine response to tration: Practical implications for cattle production within the surgical stress during different types of anesthesia and

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