Application of a topical anesthetic reduces pain-associated parameters during spermatic cord transection in piglet castration using a minimal anesthesia model

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Application of a topical anesthetic reduces pain- associated parameters during spermatic cord transection in piglet castration using a minimal anesthesia model Pauline Deffner, PhD1*; Steffanie Senf, PhD1; Anna Saller, PhD2; Julia Werner, PhD2; Judith Reiser, PhD2; Nora Abendschön, PhD1; Yury Zablotski, PhD1; Christine Baumgartner, PhD2; Mathias Ritzmann, PhD, DECPHM1; Susanne Zöls, PhD1 1Clinic for Swine, Centre for Clinical Veterinary Medicine, Ludwig Maximilian University of Munich, Oberschleissheim, Bavaria, Germany 2Center of Preclinical Research, Technical University of Munich, Munich, Bavaria, Germany *Corresponding author: Dr. Deffner (pauline.deffner@lmu.de) Received March 29, 2023 Accepted June 26, 2023 doi.org/10.2460/ajvr.23.03.0060 OBJECTIVE This study assessed the use of a topical anesthetic as a feasible approach to reduce pain during piglet castration using a minimal anesthesia protocol. ANIMALS 18 male piglets, aged 3–6 days, were included in this study. METHODS A minimal anesthetic state was induced with isoflurane administered by facemask, with anesthetic depth individu- ally adjusted based on responses to interdigital pinch. To desensitize the scrotal skin, a vapocoolant was applied 3 times. Scrotal incisions were made subsequently and Tri-Solfen (TS) or Placebo (P) was administered in both incisional gaps. After 30 seconds, the spermatic cords were severed followed by a further application of TS/P to both incision edges. Nociception-related variables, such as mean arterial blood pressure (MAP), heart rate (HR), and nocifensive movements, were assessed. RESULTS Significant differences in MAP changes were assessed between the TS (14 ± 4 mmHg) and the P group (36 ± 8 mmHg) for cutting the spermatic cords. Furthermore, significantly fewer

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MAP changes were assessed between the TS (14 ± 4 mmHg) and the P group (36 ± 8 mmHg) for cutting the spermatic cords. Furthermore, significantly fewer nocifensive movement score points appeared in the TS than in the P group (0; IQR = 0 vs 5; IQR = 6). CLINICAL RELEVANCE In this anesthesia model, the application of TS after skin incision significantly reduced MAP responses and nocifen- sive movements with spermatic cord transection compared with the application of P. However, the waiting period between TS-application and spermatic cord transection might limit the benefit of the method in conscious piglets, as pain during castration is reduced but additional stress is caused by the prolonged handling. Furthermore, using a vapocoolant did not provide anesthesia for skin incisions. T he castration of male suckling piglets is still an important issue in livestock farming. All over the world castration is commonly practiced primarily Protection Law requires pain elimination for surgical piglet castration since 2021. Nevertheless, castration of suckling piglets is still mainly carried out without ensuring constant meat quality1 and reducing the anesthesia, even though it is commonly accepted as risk of boar taint,2 but also minimizing aggressive leading to pain and distress and, therefore, reducing and sexual behavior between pigs.3,4 Some coun- animal welfare.5-8 tries in Europe have implemented the use of anes- Administration of a nonsteroidal anti-inflamma- thesia and analgesia during the castration process, tory before the castration of piglets can alleviate pain as the EU Council Directive 2018/120/EC demands after but is not able to mitigate acute pain during the better practices for castrating suckling piglets before procedure.9 Therefore, methods for controlling

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t is not able to mitigate acute pain during the better practices for castrating suckling piglets before procedure.9 Therefore, methods for controlling acute 7 days of age. For instance, in Germany, the Animal pain in this context are urgently needed. In addition, © 2023 THE AUTHORS. Published by the American Veterinary Medical Association as an Open Access article under Creative Commons CCBY-NC license. American Journal of Veterinary Research 1 Unauthenticated | Downloaded 01/26/25 02:04 AM UTC the feasibility for the farmer and the integration Therefore, the present study was performed into existing workflows are important aspects of the using a minimal anesthesia model with a low dose of practicability of pain-minimizing measures under isoflurane. As isoflurane has no analgesic potential,19 field conditions. In Australia and New Zealand, a gel- this model provides a light level of general anesthesia formulated topical anesthetic (Tri-Solfen®, Medical without analgesia, enabling differentiation between Ethics Pty Ltd) is used to provide analgesia in lambs stress- and nociception-induced responses. This and calves undergoing castration, tail docking, and investigation was part of a large-scale study on the mulesing. It contains a combination of a short-acting efficacy of local anesthesia during surgical castration (50 g/L Lidocaine hydrochloride) and a long-acting of piglets. This study part aimed to evaluate whether local anesthetic (5 g/L Bupivacaine hydrochloride), using a topical anesthetic in piglet castration is a as well as 0.048 g/L epinephrine acid tartrate as a feasible approach to reduce pain during the proce- vasoconstrictor and 5 g/L Cetrimide as an anti- dure. Therefore, the hypothesis that TS can minimize septic agent. Tri-Solfen® (TS) has been shown

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ce- vasoconstrictor and 5 g/L Cetrimide as an anti- dure. Therefore, the hypothesis that TS can minimize septic agent. Tri-Solfen® (TS) has been shown to variations in heart rate and blood pressure, as well as mitigate pain during and after various routine hus- reduce nocifensive movements during the cutting of bandry procedures in farm animals. In lambs, Paull the spermatic cords was tested in this study. et al10 documented that administration of TS in the wound together with the intramuscular application of a nonsteroidal anti-inflammatory reduced pain- Methods related behaviors in the first 4 hours after mulesing The study was performed in accordance with and peak cortisol concentrations did not differ to the EU Directive 2010/63/EU, the German Animal control animals. Treatment of 2-month-old calves Welfare Act (2018), and the ARRIVE guidelines. All immediately after dehorning with an adapted TS procedures were approved by the Ethical Committee formula (100 g/L Lidocaine hydrochloride) reduced for Animal Experiments of the Government of Upper wound sensitivity for at least 1.5 hours after the Bavaria, Munich, Germany (Reference Number procedure, suggesting less postoperative pain.11 ROB-55.2-2532.Vet_02-19-11). Regarding the castration procedure, Lomax et al12 applied TS into the scrotum of lambs during surgi- Animals cal castration before and after cutting the spermatic Eighteen clinically healthy male German cords, accompanied by tail docking. The covering of Landrace/German large white X Piétrain piglets from the spermatic cords with TS led to less pain-related 3 litters were included in this study, meeting the fol- behavior and improved wound healing. Meanwhile, lowing criteria: minimum body weight of 1.4 kg, the potential of TS for pain relief during and

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he fol- behavior and improved wound healing. Meanwhile, lowing criteria: minimum body weight of 1.4 kg, the potential of TS for pain relief during and after aged 3 to 7 days of life and no evidence of hernia or the castration of male suckling piglets has also been cryptorchidism. Neither teeth clipping, ear tagging, investigated. Assessing vocalization and defensive nor tail docking was applied to the piglets. All pig- movements during the castration procedure, Sheil lets received iron orally (1 mL per piglet; Ursoferran et al13 recorded significantly reduced nociceptive 150 mg/mL, Serumwerk Bernburg AG) during the motor and vocalization responses in piglets receiv- first 10 hours of life. Sows and piglets were housed ing TS 30 seconds before the spermatic cord transec- in the animal husbandry unit of the Clinic for Swine tion. Additionally, investigations from France, where (Oberschleissheim, Germany). Housing was in the castration of suckling piglets was performed accordance with the German Order for the Keeping using a protocol combining oral sucrose 30%, local of Productive Animals. Included piglets were ran- instillation of TS, and intramuscular Meloxicam injec- domized and distributed to 2 experimental groups. tion, piglets showed lower postoperative pain inten- Piglets of 1 group were receiving Tri-Solfen (TS), and sity than piglets of the control group (only treated piglets of the second group a Placebo (P). All partici- with Meloxicam).14 In contrast, neither a short- nor a pants involved were blinded regarding the allocation long-acting local anesthetic turned out to be effec- of the piglets to the treatment groups. tive at eliminating pain responses to castration as measured by cortisol, hematology, vocalizations, Anesthesia and behavior.15 However, in this

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oups. tive at eliminating pain responses to castration as measured by cortisol, hematology, vocalizations, Anesthesia and behavior.15 However, in this study, no waiting To measure nociception during castration, a min- time was maintained between the application of imal anesthesia protocol with isoflurane (Isoflurane the local anesthetic and spermatic cord transection; Baxter vet., Baxter Deutschland GmbH) was used thus, only conclusions on postoperative analgesia aiming to keep the piglets in a hypnotic state during could be drawn. the procedure to preclude interfering factors such Nevertheless, all available data regarding the as fear and stress. During anesthesia, animals were potential of TS to mitigate pain during and after breathing spontaneously using a circle rebreath- the castration of piglets were collected on awake ing circuit with an oxygen carrier gas flow rate of animals under farm conditions. The assessment of 3 L/min. Isoflurane was inhaled via a mask and the defensive movements during piglet castration has concentration was monitored by a connected anes- been used in a large number of studies and is consid- thetic gas monitor (Vamos® plus, Dräger Medical ered a reliable and repeatable parameter for docu- Deutschland GmbH). For achieving and maintain- menting pain responses.5,16-18 Nevertheless, there is ing light anesthesia in accordance with Guedel no feasible differentiation between pain-associated scheme III.1,20 the minimum alveolar concentration and handling-caused stress responses. of isoflurane was determined for every single piglet 2 AJVR Unauthenticated | Downloaded 01/26/25 02:04 AM UTC individually: for the induction of anesthesia 5% iso- FFP-LS and Evolution Software, FISO Technologies flurane in oxygen was administered, thereafter con-

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vidually: for the induction of anesthesia 5% iso- FFP-LS and Evolution Software, FISO Technologies flurane in oxygen was administered, thereafter con- Inc). Heart rate was determined by electrocardiog- centration was reduced while placing measurements raphy (PLUGSYS module, Transducer Amplifier mod- devices to reach the appropriate isoflurane dose. For ule TAM, heart rate module, HAEMODYN software, sustaining light anesthesia, the anesthetic depth was Hugo Sachs Elektronik–Harvard Apparatus GmbH). evaluated via interdigital pinches. For this purpose, Additionally, oxygen saturation was measured a pean clamp was closed in the interdigital space of via a pulse oximeter (2500A VET, Nonin Medical the posterior claw for a maximum of 5 seconds to a Inc) placed at the base of the piglet’s tail. Body maximum of the first locking position. A single pelvic temperature (PLUGSYS Thermocouple Amplifier limb movement with immediate calming was consid- Module (TCAM), HAEMODYN software, Hugo Sachs ered as correct anesthetic depth and isoflurane con- Elektronik—Harvard Apparatus GmbH), respira- centration was maintained. Isoflurane concentration tory frequency, and end-tidal CO2 were monitored was further reduced by 0.2% if no reaction after the (Vamos® plus, Dräger Medical Deutschland GmbH) interdigital pinch was observed. In case of excessive throughout the anesthesia period. response to the interdigital pinch, the isoflurane con- centration was increased by 0.2%. After a stabilization Local anesthesia and castration period of 3 minutes, the reaction to a further interdig- After implementing all measurement devices and ital pinch was assessed and isoflurane concentration adjusting anesthesia according to Guedel scheme was maintained or in-/decreased again depending III.1, the

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h was assessed and isoflurane concentration adjusting anesthesia according to Guedel scheme was maintained or in-/decreased again depending III.1, the castration procedure was started. A vapo- on the piglets’ movement intensity. Twenty minutes coolant spray (PreOp PLUS, chilled antiseptic for after adjusting the depth of anesthesia the castration animals, Medical Ethics Pty Ltd) that is comprising process was started with the application of a vapo- a hydrocarbon propellant in an aerosol canister and coolant spray onto the scrotal skin. This time period induces in this way a temperature reduction through was chosen because the present study was part of a evaporation of the volatile liquid spray from the skin comprehensive study and comparability with other surface, was used to anesthetize the skin. It was parts of the study had to be ensured. Afterward, skin applied 3 times to the scrotum and the residue was incisions were made, TS was applied in both cre- wiped off every time after 15 seconds. Immediately ated wound gaps and subsequently, the spermatic thereafter, 2 vertical scrotal incisions through the skin cords were severed. Anesthesia was maintained for and the processus vaginalis were made using a scal- another 90 minutes after castration before piglets pel. Thereupon, the topical anesthetic (Tri-Solfen, were euthanized intravenous with overdosed pento- Medical Ethics Pty Ltd) or P (Placebo, Medical Ethics barbital (Euthadorm 500 mg/mL; Injektionslösung, Pty Ltd) containing the same amount of epineph- CP Pharma) for obtaining the spinal cord for Fos rine was administered using an irrigation cannula analysis (findings not described in this publication). and the appropriate applicator depending on body weight: piglets less than 2 kg body weight received a

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s (findings not described in this publication). and the appropriate applicator depending on body weight: piglets less than 2 kg body weight received a Preparation nociceptive measurements total of 0.4 mL TS or P in each wound cavity, heavier After the induction of anesthesia, the setup for animals 0.8 mL per side. After a waiting period of measurement devices and preparation for the exper- 30 seconds, both spermatic cords were severed indi- imental procedure was performed as previously vidually using an emasculator. This was followed by described in detail.21-23 All animals were assumed an application of TS/P to the wound edges (0.1 mL to experience similar stress from the basic experi- or 0.2 mL per side, respectively). mental setup. Piglets were placed in a supine posi- tion and fixated in this position with warm water Heart rate and blood pressure bottles that helped to maintain a physiological body measurements temperature. Twenty minutes before general anes- During the entire procedure systolic, diastolic, thesia local anesthetic cream (Emla®, AstraZeneca and mean arterial blood pressure (MAP) were GmbH) was applied to the skin of the jugular groove. recorded using the microtip catheter in the left Eye ointment (Bepanthen Augen- und Nasensalbe, carotid artery and heart rate (HR) by using an ECG. Bayer Vital GmbH) was administered, and cot- One minute before the “events” [(1) application of ton wool was placed in the external auditory canal vapocoolant, (2) skin incision, and (3) cutting of the to avoid the impact of background noises on mea- spermatic cords] mean baseline values of MAP and surement results. The local anesthetic Lidocaine HR were calculated. Subsequently, the maximum (lidocaine 2%, Bela-pharm Arzneimittelfabrik) deviation, as well as the

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. The local anesthetic Lidocaine HR were calculated. Subsequently, the maximum (lidocaine 2%, Bela-pharm Arzneimittelfabrik) deviation, as well as the percent deviation from base- was infiltrated subcutaneous in a maximum dos- line were determined for 1 minute after the event. age of 0.3 mL in the region for the vascular access (jugular groove) before skin incision. The left carotid Nocifensive movements artery was visualized by preparation and a microtip During the application of vapocoolant, skin inci- catheter (FISO-LS Fiber Optic Pressure Catheter, sion, and cutting of spermatic cords each animal FOP-LS-2FR-10, FISO Technologies Inc) was inserted was immobilized by the same person and nocifen- for invasive systolic, diastolic, and mean arterial blood sive movements were assessed generating a noci- pressure measurement (PLUGSYS module, EIM-B, fensive score. This restraining person was blinded to EIM-A, heart rate module, HAEMODYN software, the treatment and assessed every movement of the Hugo Sachs Elektronik—Harvard Apparatus GmbH; 4 limbs and the back. Additionally, each event was AJVR 3 Unauthenticated | Downloaded 01/26/25 02:04 AM UTC recorded to confirm the assessed movements after- and “cutting of spermatic cords”; HR to events “skin ward. The scoring of nocifensive movements was incision” and “cutting of spermatic cords”), Student’s adopted from Saller et al21 and assessed for the left t-test was performed because all groups had equal and right testicles individually in terms of frequency variances (homogeneity of variance between groups and intensity of movements of all 4 legs and the was tested via Levene’s test). In the case of nonnor- back. A maximum score of 28 points (14 per testicle) mal distribution (MAP to the event skin incision;

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sted via Levene’s test). In the case of nonnor- back. A maximum score of 28 points (14 per testicle) mal distribution (MAP to the event skin incision; HR could be assigned at each event (Table 1). to event application of vapocoolant) and in ordinal data (nocifensive movements), the Mann-Whitney Table 1—Assessment of the nocifensive score. U test was used. Dichotomous variables were ana- lyzed for associations by χ2-test (nocifensive move- Leg movements score ments yes/no to the 3 events). The results are (each leg separately) Number of movements presented as violin plots. 0 No movement 1 One movement Results 2 Two or 3 movements 3 More than 3 or long- On the day of castration, piglets had an average lasting movements age of 4.6 ± 1.0 days (range = 3–6). There was no sig- Maximum leg movement score 12 nificant difference between the 2 groups. The mean Back movements score Number of movements body weight was 2.1 ± 0.3 kg (min = 1.7, max = 2.6) 0 No movement in the TS group and differed significantly (P < .05) 1 Muscle contraction from the mean body weight in the P group (mean = 2 Movements 1.8 ± 0.3 kg, min = 1.4, max = 2.4). No piglet had to Maximum back movement score 2 be excluded from the data evaluation. Maximum score per testicle 14 From the time of induction of anesthesia, until Maximum score per event 28 the castration process was started (beginning with Scoring system adopted by Saller et al21 to assess the application of the vapocoolant spray), an aver- nocifensive movements of legs and back during castration of age of 60.7 minutes (min = 48, max = 86; SD = 11.6) piglets at the 3 defined events “application of vapocoolant was needed to set all measurement devices and find spray,” “skin incision,” am “cutting of spermatic cords.” the

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ed events “application of vapocoolant was needed to set all measurement devices and find spray,” “skin incision,” am “cutting of spermatic cords.” the required anesthetic depth. On average, the iso- flurane concentration had to be adjusted 0.8 times per animal (min = 0, max = 2; SD = 0.9) to set the cor- rect anesthetic depth. The mean required end-tidal Statistics isoflurane concentration for achieving anesthesia The target value for sample size calculation was stage III.1 of the Guedel scheme was 1.4 ± 0.2% with HR immediately after castration. To demonstrate a no differences between piglets of the TS and the difference between the groups as statistically signifi- P group. For the performance of the entire castration cant, a group size of 9 animals was determined nec- procedure (including the application of vapocoolant, essary to prove a statistically significant difference in skin incisions, application of TS/P, cutting of sper- heart rate between the groups, assuming a dispersion matic cords, and second application of TS/P) a mean within groups of 90 beats/min. Because a dropout total time of 2.65 ± 0.13 min was required. The entire rate of about 10% is to be expected, 1 reserve animal anesthesia protocol lasted on average 154.2 (min = was required. Statistical significance was considered 141, max = 179; SD = 11.5) minutes before the ani- at P < .05. These statistical analyses were performed mals were euthanized for spinal cord collection. using R statistical software version 3.6.1 and IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp, Mean arterial blood pressure (MAP) Armonk). For the statistical analysis metric variables and HR were tested for normal distribution via the Shapiro- Raised mean MAP and mean HR measurements Wilk normality test.

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al analysis metric variables and HR were tested for normal distribution via the Shapiro- Raised mean MAP and mean HR measurements Wilk normality test. In normally distributed data are summarized (Table 2). The baseline mean MAP (weight; MAP to events “application of vapocoolant” for all piglets was 53 ± 16 mmHg and the mean HR Table 2—Mean values and SD of mean arterial blood pressure (MAP) and heart rate (HR) of baseline measurements before and to the time point of each defined event (“interdigital pinch,” “application of vapocoolant,” “skin incision,” and “cutting of spermatic cords”) in the 2 study groups Tri-Solfen and Placebo. Application of Interdigital pinch vapocoolant Castration Cutting of Group Parameter BL Event BL Event BL Skin incision spermatic cords Tri-Solfen (n = 9) MAP (mmHg) 56 ± 18 56 ± 18 55 ± 18 55 ± 18 55 ± 18 57 ± 207 59 ± 19 HR (bpm) 170 ± 34 170 ± 33 169 ± 30 55 ± 18 169 ± 30 168 ± 29 168 ± 27 Placebo (n = 9) MAP (mmHg) 48 ± 10 48 ± 11 47 ± 10 48 ± 10 47 ± 10 51 ± 10 60 ± 11 HR (bpm) 172 ± 27 174 ± 27 175 ± 27 176 ± 27 175 ± 273 177 ± 28 178 ± 27 BL = Baseline. 4 AJVR Unauthenticated | Downloaded 01/26/25 02:04 AM UTC was 172 ± 32 bpm and did not differ between the skin incisions provoked a mean percentual change of 2 study groups for both parameters. Regarding the 14.0 ± 6.7% (min = 5.5, max = 28.2) in MAP and 3.1 ± interdigital pinch for adjusting a light isoflurane 1.9% (min = 0.6, max = 7.0) in HR. anesthesia in accordance with Guedel scheme III.1, For the event cutting of spermatic cords the no differences were observed between the groups in percent changes of MAP and BP from baseline were changes of MAP and HR. evaluated separately in piglets of the TS and P group Percent changes of

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ps in percent changes of MAP and BP from baseline were changes of MAP and HR. evaluated separately in piglets of the TS and P group Percent changes of MAP and BP from base- (Figure 1). The MAP differed significantly (P = .000) line in piglets at the 2 defined events application between the 2 groups: the TS group showed signifi- of vapocoolant and skin incision were assessed for cantly lower maximum MAP changes (mean = 13.6%, all animals (n = 18) together, as the procedure was min = 8.8, max = 20.1; SD = 4.1) than the P group identical in both groups. The application of vapo- (mean = 35.6%, min = 24.5, max = 46.6; SD = 7.8). No coolant led to a mean percentual change in MAP and significant differences in HR deviation between the HR of 5.0 ± 2.4% (min = 0.9, max = 11.1) and 1.9 ± TS and P group were detected. 1.2% (min = 0.6, max = 4.6), respectively. Performing Nocifensive movements Applying the vapocoolant spray followed by scrotal incisions was performed identically in both study groups and led to a median of 0 (min = 0, max = 11; IQR = 1) and 1 nocifensive score points (min = 0, max = 22; IQR = 5), respectively. For cutting the sper- matic cords the intensity and frequency of limb and back movements differed significantly between the 2 study groups (Figure 1). Nocifensive scores were significantly higher (P = .05) in group P with a median score point of 5 (min = 0, max = 15; IQR = 6) than in group TS (median = 0, min = 0, max = 6; IQR = 0). Discussion The present investigation on a topical anesthetic is a small part of a large-scale study on the use of local anesthesia for pain relief in piglet castration. There have been studies on the effectiveness of TS in reducing pain during and after castration, albeit generally carried out on awake animals mostly using

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have been studies on the effectiveness of TS in reducing pain during and after castration, albeit generally carried out on awake animals mostly using defensive movements and vocalization to assess the perception of pain.13,14,24 In the present study physi- ological parameters were recorded and evaluated in addition to nocifensive movements. As these param- eters are easily influenced by other factors such as stress and fear,25 a minimal anesthesia model was chosen to be able to measure nociception by itself. To minimize litter effects and to maintain the blinding of the study-performing persons, piglets were allocated randomly to the 2 study groups. Although no difference in age was apparent between the groups, piglets belonging to the P-group had significantly lower mean body weight than those of the TS group. It can be assumed that this was a result of the small number of animals and the result- ing randomization, which could not take weight into account. Because only clinically healthy animals were included in the study and the amount of the applied TS or P was adjusted to the weight, the dif- Figure 1—Visualization of percent deviations of mean ferent weight distribution is considered nonrelevant (red dot) arterial blood pressure (A) and heart rate (B) to the results of the study. from baseline as well as nocifensive scores (C) at the Haga et al26 evaluated changes in the MAP as the event “cutting of spermatic cords” in the experimental most sensitive indicator of nociception under isoflu- groups Placebo and Tri-Solfen as violin plots. For each rane anesthesia. Accordingly, using TS for local anes- box-and-whisker plot, the solid line within the box rep- thesia, our results showed significantly decreased resents the median. The lower and upper limits of the

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sker plot, the solid line within the box rep- thesia, our results showed significantly decreased resents the median. The lower and upper limits of the box represent the interquartile (25th and 75th percen- changes in MAP during the cutting of the spermatic tiles) range, respectively. The whiskers delimit the range; cords compared with the administration of P. This is green and orange dots represent each individual piglet. in line with the results of Saller et al21 using the same AJVR 5 Unauthenticated | Downloaded 01/26/25 02:04 AM UTC minimum anesthesia model but utilizing different Although cutting the spermatic cords is con- local anesthetics for piglet castration. They analyzed sidered the most painful part of castration,8,18 skin mean percent changes in MAP of 45% following the incision for protrusion of the testicles causes pain as spermatic cord transection after injection of natrium- well. To reduce the distress caused by skin incision a chloride and significantly fewer deviations from the vapocoolant spray was used to anesthetize the skin. baseline of MAP with previous application of local Nevertheless, mean nocifensive movements were anesthesia. In our study, MAP differed from the higher during the scrotal skin incision with vapocool- mean baseline measurement by 13.6 ± 4.1% in the TS ant spray of all study animals than during cutting group, which is slightly higher than the mean change spermatic cords of piglets belonging to the TS group. in MAP (6.7%) in piglets that were only handled in Unfortunately, a control group without treatment for the study of Saller et al.21 However, this is below the scrotal incisions is missing. Vapocoolant was applied 20% deviation that is assumed as an indicative sign in both study groups (TS and P) to create uniform of

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incisions is missing. Vapocoolant was applied 20% deviation that is assumed as an indicative sign in both study groups (TS and P) to create uniform of relevant pain during a surgical procedure by Bova conditions for the subsequent cutting of spermatic et al.27 This confirms, that after an exposure time of cords as its effectiveness was not the main focus 30 seconds, TS reduced effectively nocifensive reac- of this study. Although this is limiting the results, it tions while cutting the spermatic cords, as previously should be mentioned that these findings are not in proposed by Sheil et al24 in conscious piglets. accordance with the study by Lomax et al.31 They Supporting the results of the invasive blood were able to reduce behavioral nociceptive responses pressure measurements, we detected significantly during ear notching in piglets using the same vapo- fewer nocifensive movements after the administra- coolant in comparison with untreated control ani- tion of TS than after the instillation of P while cut- mals. As the scrotum is higher perfused than the ting the spermatic cords. Defensive movements mainly cartilaginous tissue of the ear it seems likely, are already accepted as valid pain parameters.28 It that a temperature of 10 degrees, which is consid- should be noted that in the present study, the move- ered to be the threshold for an effective nerve con- ments of piglets were observed under isoflurane duction blockade,32 was not or only reached for a anesthesia. This might also affect the appearance, short time and therefore the vapocoolant was not duration, and intensity of these nocifensive move- able to achieve a sufficient effect in this region. ments. Nevertheless, the influence is classified as Performing castration with TS, a period of negligible, as for

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a sufficient effect in this region. ments. Nevertheless, the influence is classified as Performing castration with TS, a period of negligible, as for one a minimal anesthesia model 30 seconds has to be maintained after the instilla- with low-dosed isoflurane was used and for another tion of the gel formulation before the onset of effect, isoflurane was shown to have little effect on cardio- which means a prolonged fixation time. As it is com- vascular response to noxious stimuli.29 Thus, as these monly accepted that handling and restraining cause results are in line with findings of previous study stress to the animals,16 this has to be assessed as parts that demonstrated nocifensive movements a limitation of the method, as additional stress is appropriate for assessing pain perception, they con- caused by prolonged handling. firm the effectiveness of TS in reducing pain during Conclusively, under standardized conditions, spermatic cord transection.21,22 TS provided a significant reduction of nocifensive In contrast to the results of Saller et al,21 no sig- reactions while cutting the spermatic cords. In the nificant alteration in HR was observed between the minimal anesthesia model, the administration of TS 2 study groups while cutting the spermatic cords. In reduces pain-associated parameters significantly earlier studies on pain elimination during castration while cutting the spermatic cords. Nevertheless, as under isoflurane anesthesia, a significant change in TS has to be administered in the wounds and not on HR was noted in the control group during the pain- the skin surface to reach its efficacy, the skin incisions ful procedure.30 The sample size in the present study in advance of cutting the spermatic cords are still a was calculated based on these values,

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ions ful procedure.30 The sample size in the present study in advance of cutting the spermatic cords are still a was calculated based on these values, which might painful procedure. Therefore, future research should be a limitation of this study. However, in accordance focus on skin anesthesia as the use of vapocoolant in with our data, Werner et al22 were also unable to the present study was not promising. Additionally, detect any significant differences in HR deviation the postulated waiting period of 30 seconds between between the treatment and control group after cut- TS application and the cutting of the spermatic cord ting the spermatic cord using a minimum anesthesia requires a prolonged fixation, which means a higher model likewise. Nevertheless, in the present study, level of fear and stress. Therefore, there should be a as in the 2 previous parts of the study, 21,22 there was re-examination of additional value versus additional always a significant difference between the control stress using TS for castration in conscious piglets. and the group under local anesthesia concerning MAP deviations during the cutting of the spermatic Acknowledgments cords. Similarly, in studies of Haga et al,26 changes in MAP in comparison to EEG and HR were found This work was supported by the German Federal to be the most sensitive parameter for determining Ministry of Food and Agriculture (BMEL, https://www.bmel. nociception in 19 − 29 kg pigs under isoflurane anes- de). Funding was based on a decision of the Parliament of the Federal Republic of Germany, granted by the Federal Office thesia. Thus, heart rate measurements should be for Agriculture and Food (BLE, https://www.ble.de, Grant considered a less sensitive cardiovascular parameter 2817HS016, 2817HS013). than blood

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uld be for Agriculture and Food (BLE, https://www.ble.de, Grant considered a less sensitive cardiovascular parameter 2817HS016, 2817HS013). than blood pressure changes for detecting painful The authors declare no conflict of interest. Funding stimuli during the castration procedure. sources did not have any involvement in the study design, 6 AJVR Unauthenticated | Downloaded 01/26/25 02:04 AM UTC data analysis, and interpretation, or writing and publication of two topical anesthetics. Animal. 2010;4:12.2071–2079. of the manuscript. doi:10.1017/S1751731110001291 We would like to thank all persons involved in this study. 16. Leidig MS, Hertrampf B, Failing K, et al. Pain and discom- fort in male piglets during surgical castration with and without local anaesthesia as determined by vocalisation References and defence behaviour. Appl Anim Behav Sci. 2009;116(2): 174–178. doi:10.1016/j.applanim.2008.10.004 1. Škrlep M, Čandek-Potokar M, Lukač NB, et al. Comparison 17. Hansson M, Nyman G, Johansson G. Effect of local anaes- of entire male and immunocastrated pigs for dry-cured thesia and/or analgesia on pain responses induced ham production under two salting regimes. Meat Sci. by piglet castration. Acta Vet Scand. 2011;53:34. 2016;111:27–37. doi:10.1016/j.meatsci.2015.08.010 doi:10.1186/1751-0147-53-34 2. Aluwé M, Tuyttens FAM, Millet S. Field experience with 18. Abendschön N, Senf S, Deffner P, et al. Local anesthesia surgical castration with anaesthesia, analgesia, immu- in piglets undergoing castration—a comparative study to nocastration and production of entire male pigs: perfor- investigate the analgesic effects of four local anesthetics mance, carcass traits and boar taint prevalence. Animal. based on defensive behavior and side effects. Animals.

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