Optimal lameness induction model development using amphotericin B in meat goats.

Lameness continues to be a critical health and welfare concern associated with goat production. Amphotericin B (amp B) is an antimicrobial successful in inducing transient lameness for research purposes previously in livestock animals. The objectives of this study were to (1) identify which of three varying doses of amp B would be most effective in inducing lameness in meat type goats and (2) develop a facial grimace scale for goats. Lameness was produced by an intra-articular injection of amphotericin B into the left hind lateral claw distal interphalangeal joint with either a 5 mg/0.25 mL (high-low, 5 mg of amphotericin B in a volume of 0.25 mL), 5 mg/0.5 mL (high-high, 5 mg of amphotericin B in a volume of 0.5 mL), or a 2.5 mg/0.25 mL (low-low, 2.5 mg of amphotericin B in a volume of 0.25 mL). A saline treatment of 0.5 mL was used as control (0.9% sterile saline solution). Lameness response was analyzed by infrared thermography (IRT) at the induced joint, mechanical-nociception threshold (MNT), visual lameness scoring (VLS), a visual analogue scale (VAS), kinetic gait analysis (KGA), plasma cortisol (CORT), substance P (Sub P), and behavior scoring. The IRT and MNT values differed by timepoint (P ≤ 0.0001). Results from VLS showed the HL treatment was the most effective at inducing lameness (6/6 goats became lame compared to HH 4/6 and LL 2/6). At 24, 48, and 72 h, VAS scores were significantly higher when comparing HL to all other treatment groups (P = 0.0003). Both behavior observers (1 and 2) reported a significant time effect (P = 0.05), with goats exhibiting more facial grimacing at 24 h post-lameness induction. From these data, an optimal dose for a repeatable lameness induction model in goats was aquired. An effective Goat Grimace Scale (GGS) was also developed to evaluate pain responses in goats.

Comparison of lidocaine alone or in combination with a local nerve block of ethanol, bupivacaine liposome suspension, or oral meloxicam to extend analgesia after scoop dehorning in Holstein calves.

The American Veterinary Medical Association recommends the use of practices that reduce or eliminate pain and discomfort associated with dehorning. Identification of an effective, long-acting local anesthetic that is practical for producers to implement and reduces pain from dehorning would benefit animal welfare. Thirty-two Holstein bulls and heifers were enrolled. The objective of this study was to compare the efficacy and duration of activity of bupivacaine liposome suspension (BUP; n = 8), ethanol (ETH; n = 8), or meloxicam (LID + MEL; n = 8) co-administered with lidocaine compared with lidocaine only (LID; n = 8), and to quantify their effect on pain biomarkers and behaviors after scoop dehorning with cauterization in approximately 20-wk-old calves. Outcome variables collected included infrared thermography (IRT), mechanical nociceptive threshold (MNT), visual analog scale (VAS) scoring, and blood sampling for serum cortisol and prostaglandin E2 metabolites (PGEM). There was evidence of a sex effect for MNT, with bulls demonstrating a higher threshold (13.74 kgf) compared with heifers (12.12 kgf). There was a treatment by time interaction for cortisol concentrations (ng/mL). At 2 h, the BUP group had higher cortisol values (17.32 ng/mL) than the LID + MEL group (3.10 ng/mL). Heifers also had higher mean cortisol values (13.88 ng/mL) compared with bulls (6.96 ng/mL). There was a treatment by time interaction for PGEM concentration. Calves in the LID + MEL group had lower PGEM values at 4 and 8 h (10.23 and 9.12 pg/mL) than at -24, 0, and 0.5 h (20.38, 27.27, and 22.59 pg/mL, respectively). At 4 h, the LID + MEL group had lower PGEM concentrations (10.23 pg/mL) than the ETH group (27.08 pg/mL). At 8 h, the LID + MEL group had lower PGEM concentrations (9.12 pg/mL) than both the ETH and BUP groups (24.80 and 20.52 pg/mL). Thus, LID + MEL reduced cortisol and prostaglandin metabolite concentrations more effectively than ETH + LID or BUP + LID administered as a local infiltration and cornual block, respectively, before scoop dehorning followed by cauterization. The treatments administered in the present study did not seem to extend the duration of analgesia beyond the currently recommended multimodal approach, including local anesthesia and systemic analgesia such as lidocaine and meloxicam. Evidence from the current study suggests that sex influences pain biomarkers such as nociceptive threshold and cortisol concentration, with males having a higher nociceptive threshold and lower cortisol responses.

Effect of bupivacaine liposome suspension administered as a cornual nerve block on indicators of pain and distress during and after cautery dehorning in dairy calves.

Dehorning is performed on a high percentage of dairies worldwide. Concern about the negative effect of dehorning on animal welfare has contributed to the development of new guidelines that require the use of pain management at the time of disbudding in the United States. However, livestock producers are limited in how to address this requirement due to a lack of (1) approved analgesic drugs, (2) analgesic options that control pain for an extended duration, and (3) analgesic formulations that are practical for producers to administer. The objective of this study was to evaluate the effectiveness of bupivacaine liposome suspension, a novel, long-acting, local anesthetic formulation administered as a nerve block at dehorning, compared with current industry standard analgesic approaches using lidocaine nerve blocks alone or in combination with the nonsteroidal anti-inflammatory drug meloxicam. Fifty male Holstein calves, 10 to 14 wk of age, were enrolled and randomly assigned to 1 of 5 treatment groups before cautery dehorning as follows: (1) bupivacaine liposome suspension block, oral placebo (BUP); (2) lidocaine block, oral placebo (LID); (3) lidocaine block, oral meloxicam (1 mg/kg of body weight; LID + MEL); (4) saline block, oral placebo (CON); and (5) saline block, oral placebo, sham dehorn (SHAM). Biomarkers were collected from 0 to 120 h postdehorning and included infrared thermography, mechanical nociceptive threshold (MNT), pressure mat gait analysis, chute defense and behavior scoring, and blood sampling for serum cortisol and prostaglandin E2 metabolites. Responses were analyzed using repeated measures with calf nested in treatment designated as a random effect, and treatment, time, and their interaction designated as fixed effects. At 2 h postdehorning, the BUP group had a higher MNT compared with the CON group. Furthermore, at 24 h postdehorning, the BUP group had a higher MNT compared with the LID group. Gait distance differed significantly between treatment groups; the CON, LID, and LID + MEL groups had an increased gait distance relative to the SHAM group. The CON group exhibited a higher chute defense behavior score during the dehorning procedure compared with all other treatments. Furthermore, the CON group exhibited more ear flicks than the BUP and LID + MEL groups postdehorning. At 4 h and 24 h after dehorning, the LID + MEL group had a lower average prostaglandin E2 metabolites concentration compared with all other treatment groups. These data showed that administration of bupivacaine liposome suspension as a cornual nerve block at the time of dehorning was as effective at controlling pain as a multimodal approach of lidocaine and meloxicam.

Effect of bupivacaine liposome suspension administered as a local anesthetic block on indicators of pain and distress during and after surgical castration in dairy calves.

Castration is a routine procedure performed on beef and dairy operations in the United States. All methods of castration cause behavioral, physiologic, and neuroendocrine changes associated with pain. The American Veterinary Medical Association and the American Association of Bovine Practitioners recommend that anesthesia and analgesia be administered during castration. The objective of this study was to evaluate the effectiveness of bupivacaine liposome suspension, a novel, long-acting, local anesthetic formulation administered as a nerve block at castration. The authors chose to investigate this novel formulation as an alternative to the current industry standards using lidocaine nerve blocks alone or in combination with meloxicam. Thirty male Holstein calves, 16 to 20 wk of age, were enrolled and randomly assigned to one of the four treatment groups prior to surgical castration: 1) bupivacaine liposome suspension block + oral placebo (BUP), 2) lidocaine block + oral placebo (LID), 3) lidocaine block + oral meloxicam (1 mg/kg) (LID + MEL), and 4) saline block + oral placebo (CON). Biomarkers were collected at -24 h and from 0 to 120 h post-castration and included infrared thermography, pressure mat gait analysis, chute defense and behavior scoring (pain and activity), and blood sampling for serum cortisol and prostaglandin E2 metabolites (PGEMs). Responses were analyzed using repeated measures, with calf nested in treatment as a random effect, and treatment, time, and their interaction designated as fixed effects. The results from pressure mat gait analysis show that the CON had a shorter front limb stance time from baseline (-8.73%; 95% confidence interval [CI]: -24.84% to 7.37%) compared with BUP and LID + MEL (>5.70%; 95% CI: -22.91% to 23.79%) (P < 0.03). The CON tended to have an increase in front limb force from baseline (6.31%; 95% CI: -1.79% to 14.41%) compared with BUP, LID, and LID + MEL (<-5.06%; 95% CI: -14.22% to 0.95%) (P < 0.04). The CON displayed higher counts of hunched standing (2.00; 95% CI: 1.68 to 2.32) compared with LID + MEL (1.43; 95% CI: 1.13 to 1.72) (P = 0.05). The CON had higher cortisol concentrations at 24 h (7.70 ng/mL; 95% CI: 1.52 to 13.87 ng/mL) relative to BUP (3.11 ng/mL; 95% CI: -2.56 to 8.79 ng/mL) (P = 0.002). At 4 and 24 h, LID + MEL had lower PGEM concentrations from baseline (-32.42% and -47.84%; 95% CI: -78.45% to -1.80%) compared with CON (27.86% and 47.63%; 95% CI: 7.49% to 82.98%) (P < 0.02). The administration of bupivacaine liposome suspension as a local anesthetic block at the time of castration was as effective at controlling pain as a multimodal approach of lidocaine and meloxicam.

Castration is a routine procedure performed on beef and dairy operations in the United States. All methods of castration cause pain. The American Veterinary Medical Association and the American Association of Bovine Practitioners recommend that anesthesia and analgesia be administered during castration. The objective of this study was to evaluate the effectiveness of bupivacaine liposome suspension, a novel, long-acting, local anesthetic formulation administered as a nerve block at castration, as an alternative to current industry standards using lidocaine nerve blocks alone or in combination with meloxicam. Evidence provided in the current study demonstrates that pain from surgical castration can last up to 120 h post-castration, indicated by changes in ocular temperature, gait analysis, and prostaglandin metabolite concentrations. These data show that the administration of bupivacaine liposome suspension as a local anesthetic block at the time of castration was as effective at controlling pain as a multimodal approach of lidocaine and meloxicam. A single injection that alleviates both perioperative and postoperative pain would be an attractive option for livestock producers to alleviate pain at the time of castration. Further research is needed to discover effective ways of managing pain for extended durations following painful husbandry procedures.

Proposed multidimensional pain outcome methodology to demonstrate analgesic drug efficacy and facilitate future drug approval for piglet castration.

Castration of male piglets in the United States is conducted without analgesics because no Food and Drug Administration (FDA) approved products are labeled for pain control in swine. The absence of approved products is primarily due to a wide variation in how pain is measured in suckling piglets and the lack of validated pain-specific outcomes individually indistinct from other biological responses, such as general stress or inflammation responses with cortisol. Simply put, to measure pain mitigation, measurement of pain must be specific, quantifiable, and defined. Therefore, given the need for mitigating castration pain, a consortium of researchers, veterinarians, industry, and regulatory agencies was formed to identify potential animal-based outcomes and develop a methodology, based on the known scientific research, to measure pain and the efficacy of mitigation strategies. The outcome-based measures included physiological, neuroendocrine, behavioral, and production parameters. Ultimately, this consortium aims to provide a validated multimodal methodology to demonstrate analgesic drug efficacy for piglet castration.Measurable outcomes were selected based on published studies suggesting their validity, reliability, and sensitivity for the direct or indirect measurement of pain associated with surgical castration in piglets. Outcomes to be considered are observation of pain behaviors (i.e. ethogram defined behaviors and piglet grimace scale), gait parameters measured with a pressure mat, infrared thermography of skin temperature of the cranium and periphery of the eye, and blood biomarkers. Other measures include body weight and mortality rate.This standardized measurement of the outcome variable's primary goal is to facilitate consistency and rigor by developing a research methodology utilizing endpoints that are well-defined and reliably measure pain in piglets. The resulting methodology will facilitate and guide the evaluation of the effectiveness of comprehensive analgesic interventions for 3- to 5-day-old piglets following surgical castration.

Technical contribution: use of continuous recording video monitoring of maintenance and pain behaviors in piglets after surgical castration to validate six continuous time sampling periods for behavior scoring.

Castration is a painful procedure routinely performed on piglets. Specific periods relative to castration and time sampling rules are used widely to quantify deviations in piglet's behavior associated with castration rather than assessing behavior for the entire trial period. However, very limited work has evaluated time sampling recording rules to quantify behavioral changes to piglets undergoing castration. Therefore, the objective of this study was to validate the accuracy of six continuous time sampling periods (5, 10, 15, 20, 30, and 45 min), to quantify piglet behavior post-castration when compared with a full 60-min observation period. Sixteen Yorkshire-Landrace x Duroc piglets were surgically castrated. Data were collected using continuous observation (recording rule) of each individual male piglet per litter for 60-min post-castration. The 60-min continuous behavioral data set was then subdivided into six data subsets for each defined continuous time sampling period (5, 10, 15, 20, 30, and 45 min). Data from each continuous time sampling period and the full period data were analyzed using both a generalized linear mixed model and linear regression analysis. For the generalized linear mixed model, 30- and 45-min continuous time sampling periods were not different (P > 0.05) when compared with the full observation period data for all behaviors. For the linear regression analysis, affiliative interaction, sitting, walking, huddled up, prostrated, scratching, spasms, and trembling behaviors met the pairwise comparison accuracy criteria: [1) the coefficient of determination (R2) was > 0.90, 2) the intercept did not differ from 0 (P > 0.05), and 3) the slope did not differ from 1 (P > 0.05)] at the 45-min continuous time sampling period compared to full observation period. Results from this study suggest that a 45-min continuous time sampling period would be necessary to accurately investigate piglet behavior during the acute pain sensitivity time post-castration when considering both maintenance and pain-associated behaviors.

Analgesic Comparison of Flunixin Meglumine or Meloxicam for Soft-Tissue Surgery in Sheep: A Pilot Study.

The amount of scientific data evaluating sheep pain responses after analgesia treatment is limited. The aims of this study were to compare the efficacy of flunixin meglumine (FLU) and meloxicam (MEL) at relieving post-surgical pain in sheep and to evaluate the utility of the Sheep Grimace Scale (SGS). Thirty ewes were assigned to one of three treatment groups: oral MEL or intravenous FLU to manage pain associated with a laparotomy procedure, or a non-surgical control (CON) group. Behavior and physiologic outcome measures were collected pre-procedure and up to 48 h post-procedure. There were no significant differences in behavior, gait, degree of inflammation or pain around the surgical site when MEL and FLU sheep were compared, suggesting that both drugs provided similar levels of analgesia. Significant differences in behavior, gait, abdominal inflammation and pain were found when surgical sheep were compared to non-surgical controls. More work is needed to characterize the amount of pain relief provided by MEL and FLU. The SGS had moderate reliability between scorers; however, the results were inconsistent with the other study outcome measures. The SGS may have some utility as a pain assessment tool but should be used in conjunction with other pain measures.

Evaluating the utility of a CO2 surgical laser for piglet castration to reduce pain and improve wound healing: a pilot study.

CO2 surgical lasers are widely used for procedures in veterinary and human medicine. There is evidence to suggest surgery using a CO2 laser reduces pain and swelling and improves healing time compared with surgery with a scalpel. Millions of piglets in North America are surgically castrated each year using a scalpel. Therefore, piglet welfare may be improved by making refinements to the surgical procedure. The objectives of this preliminary study were to determine the ability of a CO2 surgical laser to (1) reduce pain and (2) improve wound healing of piglets undergoing surgical castration. Two-day-old male Yorkshire × Landrace piglets were used and randomly assigned to 1 of 3 treatments (n = 10 piglets/treatment group): surgical castration with the CO2 laser, surgical castration with a scalpel, or sham (uncastrated control). Piglets were video recorded in their pens for 1 hr preprocedure and from 0 to 2, 6 to 8, and at 24 hr postprocedure for behavior scoring. Surgical site images were collected at baseline, 0, 8, 24, 48, 72, 96, 120, 144, and 168 hr postcastration for wound healing assessment. Infrared thermography images of the surgical site were also taken at baseline, 0, 0.5, 8, and 24 hr postprocedure to assess inflammation. Finally, blood was collected from each piglet at baseline and 0.5 hr postcastration to assess cortisol levels, prostaglandin E metabolite and pig-major acute phase protein concentration. Laser-castrated piglets displayed more pain behaviors across the observation period than scalpel-castrated piglets (P = 0.05). Laser-castrated piglets also displayed significantly more agonistic behavior than both scalpel-castrated piglets (P = 0.005) and sham piglets (P = 0.036); yet, laser-castrated piglets had significantly lower temperatures at the site of incision compared with scalpel-castrated piglets (P = 0.0211). There was no significant difference in wound healing or any of the blood parameters assessed between laser-castrated and scalpel-castrated piglets. There was evidence of thermal tissue damage on the scrotum of piglets that were castrated using the CO2 laser. This may have resulted in the unremarkable healing time and the increased pain behavior observed in this study. The surgical laser technique should be refined before conclusions can be made regarding the utility of a CO2 laser for piglet castration.

Use of Meloxicam or Ketoprofen for Piglet Pain Control Following Surgical Castration.

Surgical castration of piglets is performed routinely on commercial pig farms, to prevent boar taint and minimize aggression. While this procedure is known to be painful, piglets are generally not provided any analgesic for pain relief, leading to welfare concerns. The objectives of this study were to assess the efficacy of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam (MEL) (0.4 mg/kg or 1.0 mg/kg) and ketoprofen (KET) (6.0 mg/kg) in reducing behavioral indicators of pain in castrated piglets. This study also examined the utility of the Piglet Grimace Scale (PGS) as a pain assessment tool. Nineteen litters of 5-days-old male piglets (n = 120) were used and piglets within a litter were randomly assigned to one of eight possible treatments: 0.4 mg/kg MEL-castrated or uncastrated, 1.0 mg/kg MEL-castrated or uncastrated, 6.0 mg/kg KET-castrated or uncastrated, saline (castrated control), or sham (uncastrated control). Treatments were administered intramuscularly (IM) 20 min prior to surgical castration. Piglets were video recorded for 1 h pre-procedure, for 8 h immediately post-castration and for another hour, 24 h post-procedure. Twenty-one behaviors and postures were scored continuously for the first 15 min of each hour and 1,156 still images of piglet faces were collected and scored using the PGS. Within each treatment group post-castration, castrated piglets displayed significantly more pain-related behaviors than uncastrated piglets (0.4 mg/kg MEL: p = 0.0339, 1.0 mg/kg MEL: p = 0.0079, 6.0 mg/kg KET: p = 0.0034, Controls: p < 0.0001). Castrated piglets also grimaced significantly more post-procedure than uncastrated piglets (p = 0.0061). Compared to the castrated control, none of the NSAID treatments significantly reduced piglet pain behaviors (0.4 mg/kg MEL: p = 1.0000, 1.0 mg/kg MEL: p = 0.9995, 6.0 mg/kg KET: p = 0.4163) or facial grimacing. Piglets demonstrated significantly more pain behaviors 24 h post-castration than at all other time points (p < 0.0001). The PGS was a less effective measure to detect acute pain; however, our findings suggest it does have utility as a pain assessment tool in neonatal pigs. Our findings also indicate that the use of these NSAIDs were ineffective at alleviating castration-associated pain in piglets.

Efficacy of buprenorphine for management of surgical castration pain in piglets.

BACKGROUND: Surgical castration is a painful procedure, performed routinely on commercial pig farms to prevent boar taint and reduce aggression. The objectives of this study were to assess the efficacy of 0.04 mg/kg buprenorphine (BUP) in reducing pain in castrated piglets, using behavioral indicators and vocalization analysis. This study also sought to further validate the Piglet Grimace Scale (PGS) as a pain assessment tool. A pilot study first assessed the safety of BUP or 0.2 mg/kg butorphanol administration to piglets (n = 4 per treatment). When no side effects were noted with BUP, ten litters of 5-day old piglets (n = 60 total, 15 per treatment group) were used, and randomly assigned to one of four possible treatments: BUP (castrated or uncastrated), saline, or sham. Treatments were administered as an intramuscular injection 20 min prior to surgical castration. Piglets were video recorded 1 h pre-procedure, post-castration for 8 h and for another hour, 24 h post-procedure. Behaviors were scored continuously for the first 15 min of each hour and 511 still-images of piglet faces were scored using the PGS. Vocalizations were recorded from each piglet at three points in the study: at initial handling, injection, and castration. RESULTS: Butorphanol caused some piglets to become groggy and vomit and was not further evaluated. BUP-castrated piglets demonstrated significantly fewer pain behaviors and less facial grimacing compared to saline-treated pigs (P < 0.0001 and P = 0.0073, respectively). There was no difference between the pain behaviours displayed by BUP-castrated piglets compared to BUP-uncastrated and sham piglets (P = 0.9986 and P = 0.7484). There was also no difference in PGS score between BUP-castrated and BUP-uncastrated piglets (P = 0.9376). Piglets in the BUP-castrated group produced vocalizations of similar frequency, amplitude, power, and energy to saline-treated piglets. CONCLUSIONS: Buprenorphine was highly effective in alleviating castration-associated pain behaviors and facial grimacing in piglets, without causing any obvious side effects. Its administration did not reduce piglet vocalizations at the time of castration. The PGS corresponded well to piglet pain behaviors and has utility as a pain assessment tool.

Development of a Piglet Grimace Scale to Evaluate Piglet Pain Using Facial Expressions Following Castration and Tail Docking: A Pilot Study.

Facial expressions are increasingly being used to assess pain in non-human species, including rodents, horses, and lambs. The development of these species-specific grimace scales has allowed for more rapid pain detection, which can lead to better animal welfare if intervention promptly occurs. For grimace scales to ever be used as a stand-alone measure of pain, it is important they correlate with established pain assessment tools, such as behavioral analysis. This preliminary study aimed to determine whether piglets exhibit pain grimacing and if these facial expressions correlate with their behavior. It also assessed and compared the behavior of boar piglets given an analgesic and topical anesthetic prior to surgical castration and tail docking to piglets that did not receive anything for pain relief. Five-day-old male Yorkshire piglets (n = 19) from four pens were randomly assigned, within their pen, to one of five possible treatments: meloxicam (0.4 mg/kg, intramuscularly) + EMLA® cream, meloxicam (0.4 mg/kg, intramuscularly) + non-medicated cream, saline (intramuscularly) + EMLA® cream, saline (intramuscularly) + non-medicated cream, or no treatment prior to surgical castration and tail docking. Piglet behaviors were video recorded for 8 h immediately after castration, as well as for 1 h at 24 h pre- and post-castration. Their individual behaviors were scored continuously for the first 15 min of every hour of video collected. Facial images were also captured across all time points. A Piglet Grimace Scale (PGS) was developed and used by two observers blinded to treatment, time, and procedure to score over 600 piglet faces. All piglets displayed significant behavioral changes up to 7 h post-castration when compared to baseline, and the use of meloxicam and EMLA® cream was not associated with a reduction in painful behaviors. Significantly higher PGS scores were noted at 0, 3, 4, and 5 h post-castration when compared to PGS scores at 7 h and there was no effect of treatment. PGS scores significantly correlated with piglet behavioral activity. The results suggest that the PGS may have utility for pain evaluation in neonatal pigs.