Efficacy of meloxicam in a pain model in sheep.

OBJECTIVE: To evaluate the efficacy of the non-steroidal anti-inflammatory drug, meloxicam, in alleviating pain and inflammation and on production-related variables in a model of sterile acute inflammation in sheep. METHODS: Groups of 12 mature Merino ewes received 0, 0.5, 1.0 or 1.5 mg/kg meloxicam subcutaneously 90 min before injection of 0.1 mL turpentine subcutaneously on the anterior aspect of the proximal phalanx of a forelimb. Pain- and inflammation-related variables were assessed at -18, 3, 6, 9, 12, 24, 48 and 72 h relative to meloxicam administration. Daily feed intake and body weight change 7 days later were also assessed. Pain-related variables measured were weight borne on each forelimb, lameness score, time each forelimb was raised in a 20-s interval and tolerance to a noxious mechanical stimulus. Inflammation-related variables measured were skin temperature, limb circumference, body temperature, plasma haptoglobin concentration and peripheral blood leucocyte parameters. RESULTS: Meloxicam was effective in improving all pain-related variables. A dose-dependent response was seen between 0 and 1.0 mg/kg, with no additional benefit provided by 1.5 mg/kg. At a dose rate of 1.0 mg/kg, meloxicam improved weight borne on the turpentine-treated limb by 14%, reduced the time the treated limb was held in a non-weight-bearing posture by 46%, reduced the lameness score by 58% and improved tolerance to pressure by 52%. No significant effects of meloxicam on inflammatory variables or appetite were observed. CONCLUSIONS: Using a validated pain model, the data suggested that 1.0 mg/kg meloxicam provided significant analgesic benefits to sheep.

Effect of local infusion of NSAID analgesics administered alone or in combination on the pain associated with band castration in calves.

OBJECTIVE: To evaluate the analgesic efficacy of flunixin alone or in combination with diclofenac administered locally to the scrotum at the time of band castration of calves. METHODS: Angus bull calves (n = 40; ≈7-9 weeks old) were allocated to four treatment groups (n = 10 per group) to examine the effects of two non-steroidal anti-inflammatory analgesics (NSAIDs) administered locally at the time of band castration: sham control; castration + flunixin; castration + flunixin + diclofenac; castration + saline. The NSAIDs and saline were administered subcutaneously into the scrotum under the band. Blood was sampled at -0.5, 0.5, 1.5, 3, 12, 24, 48 and 72 h relative to castration. Haematology parameters and plasma cortisol levels were determined in samples at all time points and plasma haptoglobin levels determined in samples collected at -0.5, 24, 48 and 72 h. Pain avoidance and postural behaviours were measured for 2 and 12 h, respectively, after castration. RESULTS: Band-castrated calves exhibited significantly higher peak cortisol and higher integrated cortisol responses during the first 6 h post-castration relative to sham controls. Individual active pain avoidance behaviours observed for 1 h post-castration were not significantly different between treatment groups; however; the sum of the total behaviours was significantly increased by castration (P = 0.023). Postural changes included increased abnormal ventral lying for all castrated groups and decreased normal standing and increased combined abnormal postures for the flunixin- and saline-treated groups. Growth rates of calves were not affected by treatments during weeks 1 and 2 post-castration; however, growth rates of castrated calves were significantly lower than those of sham-treated calves in week 3 post-castration (1.41 vs 0.84, 0.75 and 0.56±0.19 kg/day for sham, flunixin-, flunixin + diclofenac- and saline-treated groups, respectively). CONCLUSIONS: The administration of flunixin or flunixin + diclofenac intrascrotally at several sites at the time of banding did not improve the welfare of young Angus bull calves undergoing this method of castration when assessed by both physiological and behavioural parameters. In this study, band castration at 7-9 weeks of age had less effect compared with results for older calves reported previously. Further research is required to develop effective analgesic treatments that can be administered at the time of castration to large numbers of animals.

Development of a lameness model in sheep for assessing efficacy of analgesics.

OBJECTIVE: To develop a lameness model to assess the efficacy of analgesics for alleviating pain, swelling and systemic signs of inflammation in sheep. PROCEDURES: The response to subcutaneous injection of 0.1 or 0.2 mL turpentine in a forelimb pastern (n = 4 ewes per dose) was examined at 0, 3, 6, 24, 48 and 72 h. In a second experiment, responses were measured at 0, 2, 4, 6, 8, 10, 12 and 24 h in ewes receiving 0.1 mL turpentine ± meloxicam 1 mg/kg IV at 0 h (n = 6 per group). Responses measured included forceplate pressure, skin temperature, limb circumference, nociception, leucocyte count, neutrophil : lymphocyte ratio, haptoglobin and daily feed intake. RESULTS: Turpentine injection caused a decrease in weight borne on the treated limb, increased skin temperature, increased sensitivity at the injection site and leucocytosis by 2 h and increased limb circumference by 4 h. Weight borne and sensitivity of the injected limb returned to control levels after around 24 h, whereas tissue swelling, elevated skin temperature and elevated haptoglobin levels persisted for at least 72 h. Treatment with meloxicam improved weight borne by and tolerance to pressure exerted on the turpentine-injected limb. CONCLUSIONS: The local and systemic signs of inflammation and pain, temporary reduction in function of the affected limb and partial amelioration of some of these changes by the dose of meloxicam used here suggest that injection of turpentine in the lower forelimb provides a suitable model for examining the efficacy of analgesics for alleviation of pain and inflammation in sheep.

Physiological and behavioural effects of intradermal injection of sodium lauryl sulfate as an alternative to mulesing in lambs.

OBJECTIVE: To assess the effects on physiology and behaviour of intradermal injection of sodium lauryl sulfate (SLS) as an alternative to mulesing. PROCEDURES: Three groups of Merino lambs were studied: Control (n = 10), SLS (n = 11) and Mulesed (n = 11). The SLS group received SLS (7% w/v) and benzyl alcohol (20 mg/mL) in phosphate buffer, and the Mulesed group received 6 mL topical local anaesthetic as a wound dressing. Haematology, cortisol, beta-endorphin and haptoglobin concentrations, rectal temperatures, body weight and behaviours were monitored for up to 42 days post treatments. RESULTS: SLS treatment induced mild swelling followed by thin scab formation. Fever (>40°C) was observed at 12 and 24 h, cortisol concentration was elevated on days 1 and 2, haptoglobin concentration was highly elevated on days 2-7, white blood cell count was elevated on days 2 and 4 post treatment, but average daily gain was not affected. Fever at 12 h was significantly higher in the SLS than in the Mulesed group, whereas maximum temperature, temperature area under the curve (AUC), occurrence of fever, cortisol profile, cortisol AUC, white blood cell counts and haptoglobin concentrations until day 7 were comparable. The behaviours of normal standing, total standing and total lying were modified for 2 days by SLS treatment, but changes were less marked and of shorter duration than in the Mulesed group. On day 1, the SLS group spent <5% of time in total abnormal behaviours compared with 18% in the Mulesed group. The SLS group tended to spend more time in abnormal behaviours on day 1 than the Controls. CONCLUSIONS: The behaviour of the SLS group was similar to that of the unmulesed Controls and their physiological responses were intermediate between the Mulesed lambs receiving post-surgical analgesia and the Controls.

Needle-free vaccination in sheep.

Multi-dose vaccinators have been in use for many years to vaccinate livestock. A number of needle-free vaccinators that use compressed gas to drive the vaccine through intact skin have been recently introduced to the market. We recently examined the efficacy of a needle-free vaccinator to induce antibodies to tetanus toxoid in sheep. The result indicates that needle-free vaccination can stimulate antibody responses comparable to conventional needle vaccination.

The effects of 12, 30, or 48 hours of road transport on the physiological and behavioral responses of sheep.

To identify long-distance transport durations compatible with acceptable animal welfare, the aim of this study was to determine the responses of healthy sheep to road transport under good conditions for 12, 30, or 48 h. Merino ewes (n = 120; 46.9 +/- 0.39 kg) were allocated to road transport treatments of 12, 30, or 48 h, with 2 replicates per treatment. Blood and urine samples and BW were taken pretransport and at 0, 24, 48, and 72 h posttransport. Lying time was measured using data loggers. Increasing transport durations resulted in reduced (P < 0.001) BW and increased (P < 0.05) hemoconcentration, but these effects did not exceed clinically normal ranges for any transport duration, and sheep generally recovered to pretransport values within 72 h posttransport. Sheep transported for 30 and 48 h had less BW on arrival than sheep transported for 12 h (P < 0.001). There were no differences (P > 0.05) between the 12- and 30-h treatments in sheep BW at 24, 48, or 72 h after arrival. Sheep transported for 30 and 48 h had greater total plasma protein concentrations on arrival than sheep transported for 12 h (P < 0.001). Although the white cell count and neutrophil:lymphocyte ratio increased with transport, there were no consistent effects of transport duration. There were also no effects (P = 0.10) of transport duration on plasma cortisol concentrations. There were no treatment differences (P > 0.05) in lying times during the first 18 h after arrival. Sheep transported for 30 or 48 h lay down less (P < 0.05) than sheep transported for 12 h between 18 and 24 h after arrival, but there were no other differences over 72 h. These findings indicate that healthy adult sheep, transported under good conditions, can tolerate transport durations of up to 48 h without undue compromise to their welfare.

Effects of a topical anaesthetic formulation and systemic carprofen, given singly or in combination, on the cortisol and behavioural responses of Merino lambs to castration.

OBJECTIVE: To determine the effectiveness of a topical anaesthetic formulation (Tri-Solfen) with or without the administration of a non-steroidal anti-inflammatory drug (carprofen) on the pain and distress response associated with ring or surgical castration of ram lambs. PROCEDURES: Merino ram lambs (n = 78) were allocated to 10 treatment groups: 4 groups of knife-castrated lambs and 4 groups of ring-castrated lambs received carprofen (4 mg/kg SC) and Tri-Solfen; 2 control groups (sham) received carprofen at 0 or 4 mg/kg SC. Measurements included plasma cortisol and haptoglobin concentrations, haematology, and behaviour, including posture. RESULTS: Knife-castrated lambs had higher peak cortisol and integrated cortisol responses for the first 6 h after treatment and greater concentration s of circulating acute phase proteins than ring-castrated lambs, both of which were significantly different from the sham controls. Tri-Solfen applied to the knife castration wound significantly reduced both the peak plasma cortisol concentration and the integrated cortisol response for the first 6 h and improved lying behaviour in the first 12 h. Carprofen reduced the cortisol response to knife castration at 30 min, but elevated the cortisol responses at 24 and 48 h. Carprofen nearly halved the number of acute pain behaviours associated with ring castration. There were no significant additive or synergistic effects from combining the analgesic treatments. Tri-Solfen applied to the tail wound provided no detectible benefits during ring castration + tail docking. CONCLUSIONS: The physiological and behavioural responses suggest that ring castration has less impact on the lamb than knife castration. The specific analgesic treatments can provide modest amelioration of the pain and discomfort associated with castration. Alternative doses or application methods may enhance their efficacy.

Assessment of welfare of suckling lambs following intradermal injection of cetrimide as a non-surgical alternative to conventional mulesing.

OBJECTIVE: To assess in suckling lambs the impact of intradermal injection of cetrimide, a quaternary ammonium compound formulated to induce non-surgical mulesing, on some physiological and behavioural indicators of welfare. PROCEDURES: We allocated 32 suckling lambs (9-11 weeks old) to three groups: (1) control (n = 10), (2) conventional surgical mules (n = 11) and (3) non-surgical mules (n = 11). Non-surgical mulesing was induced by intradermal injection of 4% (w/w) cetrimide + 3% (w/w) polyvinylpyrrolidone in water. Lambs were run in pens of four together with their dams. Haematology, cortisol, beta-endorphin and haptoglobin levels, and rectal temperature were monitored at least daily for the first 7 days after treatment, then weekly until day 28. Body weight was measured weekly and behaviour was measured every 15 min for 12 h on the day of treatment, then on days 1, 2, 4, 6, 12, 21 and 28 following treatment. RESULTS: The intradermal treatment induced local tissue swelling, systemic signs of severe inflammation, including high fever (> 41.0 degrees C) and elevated blood cortisol levels, by 12 h. Rectal temperatures were significantly elevated until 6 days after treatment, cortisol levels were elevated until 4 days after treatment, haptoglobin levels for at least 7 days after treatment and the neutrophil to lymphocyte ratio until 5 days after treatment. Peak cortisol values were comparable in mulesed lambs and lambs receiving the intradermal treatment, whereas the areas under the curves for cortisol and temperature were greater in lambs receiving the intradermal treatment than in mulesed lambs. Beta-endorphin levels were significantly elevated in mulesed sheep at 12 h. There was no effect of intradermal treatment on average daily gain, fibre diameter or beta-endorphin concentration. Mulesed lambs spent 44% of the time in abnormal behaviours (hunched standing, stiff walking, pawing, lateral lying and lying intention) on the day of treatment. On the day after treatment, lambs receiving the intradermal treatment spent 11% of the time (comparable to mulesed lambs) in abnormal behaviours. In comparison, control lambs spent 0.4% of their time in abnormal behaviours on the same day. CONCLUSIONS: The welfare of suckling lambs that were non-surgically mulesed by intradermal injection of cetrimide was measurably poorer than control lambs.

Effect of the non-steroidal anti-inflammatory drug, carprofen, on weaned sheep following non-surgical mulesing by intradermal injection of cetrimide.

OBJECTIVE: To assess in weaned lambs the palliative effects of the non-steroidal anti-inflammatory drug, carprofen, following intradermal injection of cetrimide to induce non-surgical mulesing. PROCEDURES: We allocated 40 weaned lambs (20-22 weeks old) to four groups of 10 animals: (1) control, 2) conventional surgical mules, (3) intradermal treatment and (4) intradermal treatment + carprofen. Non-surgical mulesing was induced by intradermal injection of 4% (w/w) cetrimide + 3% (w/w) polyvinylpyrrolidone in water. In group 4, carprofen (4 mg/kg, SC) was administered 1 h before intradermal treatment. Five weaners, including an animal from each treatment, were run in each pen. Neutrophil to lymphocyte ratio, cortisol, beta-endorphin and haptoglobin levels and rectal temperature were monitored at least daily for the first 7 days after treatment, then weekly until day 28. Body weight was measured weekly and behaviour was measured every 15 min for 12 h on the day of treatment, then on days 1, 2, 4, 6, 12, 21 and 28 following treatment. RESULTS: The intradermal treatment resulted in high fever and elevated blood cortisol by 12 h. Rectal temperatures were significantly elevated until 5 days after treatment, cortisol was elevated until 3 days after treatment, haptoglobin for at least 7 days after treatment and the neutrophil to lymphocyte ratio until 4 days after treatment. Average daily gain was depressed in the week following treatment. Abnormal behaviours (hunched standing, stiff walking, pawing, lateral lying and lying intention) were increased on the day of treatment and for 6 days post treatment. Carprofen reduced the time spent in abnormal behaviours by approximately two-thirds but did not ameliorate the physiological responses to the intradermal treatment. CONCLUSIONS: In weaner sheep, carprofen ameliorated the behavioural responses, but was unable to provide relief from the intense and sustained physiological responses to non-surgical mulesing by intradermal injection of cetrimide. Systemic side-effects may be unavoidable with formulations based on quaternary ammonium compounds that are designed to reduce the risk of fly strike in sheep by remodelling breech tissue through induction of tissue necrosis.

Effects of meloxicam or tolfenamic acid administration on the pain and stress responses of Merino lambs to mulesing.

OBJECTIVE: To determine the effectiveness of two long-acting non-steroidal anti-inflammatory drugs (NSAIDs) at reducing the pain and stress responses to mulesing in lambs. PROCEDURES: Merino lambs (n = 60) were allocated at 5 weeks of age to six treatment groups: (1) sham mules; (2) mules; (3) tolfenamic acid-sham mules; (4) tolfenamic acid administered 45 min before mulesing; (5) tolfenamic acid at the time of mulesing; (6) meloxicam at the time of mulesing. Plasma cortisol was measured at -0.75, -0.25, 0, 0.5, 1, 3, 6, 12, 24, 48 and 72 h relative to mulesing. Beta-endorphin concentrations in plasma were determined at 0, 0.5, 1, 6, 12, 24, and 48 h. Haematology was performed on blood samples taken at -0.75, 0, 24, 48 and 72 h. Plasma haptoglobin was measured at 0, 12, 24, 48 and 72 h. Rate of wound healing was determined 72 h post mulesing, and animal behaviour, including posture, was measured for 6 h after mulesing. RESULTS: The mulesed lambs exhibited large increases in plasma concentrations of cortisol, beta-endorphin and haptoglobin. All mulesed animals lost weight significantly in the week after mulesing, regardless of analgesic administration, but the difference in weight between mulesed and unmulesed lambs was less at the final measurement, 2 weeks after mulesing. Mulesed lambs spent significantly less time lying ventrally than control lambs. All lambs that were mulesed, including those administered NSAIDs, spent more time standing with a hunched posture and less time walking normally than control lambs. CONCLUSIONS: The NSAID treatments applied 45 min before or at the time of mulesing at the dose levels used in this study were not effective in reducing the acute response of lambs to mulesing.

The effect of a topical anaesthetic formulation, systemic flunixin and carprofen, singly or in combination, on cortisol and behavioural responses of Merino lambs to mulesing.

OBJECTIVE: To determine the pain responses of lambs to mulesing, and the effectiveness of potential analgesic treatments. PROCEDURES: Merino lambs (n=64) were allocated at 5 weeks of age to eight treatment groups: 1) sham mules; 2) conventional mules; 3) topical anaesthetic, incorporating lignocaine, bupivicaine, adrenaline and cetrimide, applied immediately after mulesing; 4) flunixin + topical anaesthetic, with flunixin administered 2.5 mg/kg s.c. 90 min before mulesing; 5) carprofen + topical anaesthetic, with carprofen administered 4 mg/kg s.c. 90 min before mulesing; 6) carprofen, administered as above; 7) flunixin, administered as above; and 8) carprofen + flunixin, administered as above. Plasma cortisol was measured at 0, 0.5, 6, 12 and 24 h relative to mulesing. Animal behaviour, including posture, was recorded for 12 h after mulesing. RESULTS: The conventional mules lambs exhibited large increases in plasma cortisol, reduced lying and increased standing with a hunched back compared with sham mules animals. Topical anaesthetic reduced the cortisol peak to mulesing and hunched standing, and increased lying compared with the conventional mules treatment, but generally did not result in values equivalent to sham mules animals. Carprofen, flunixin, and carprofen + flunixin treatments did not reduce the cortisol response to mulesing but substantially ameliorated some changes in behavioural postures. Flunixin + topical anaesthetic reduced the cortisol peak following mulesing and substantially ameliorated most changes in behavioural postures. Carprofen + topical anaesthetic abolished the cortisol peak following mulesing and substantially ameliorated most changes in behavioural postures. All mulesed animals lost weight in the week after mulesing regardless of analgesic administration, but there were no significant differences in growth rate between any of the eight treatments over the 3 weeks after mulesing. CONCLUSIONS: Analgesics can moderate the pain response of lambs to mulesing. The welfare outcome for lambs of mulesing could be improved by use of a combination of local anaesthetic and long acting non-steroidal anti-inflammatory drug.

Immunization of sheep against GnRH early in life: effects on reproductive function and hormones in rams.

Groups of Merino ram lambs were immunized against GnRH either soon after birth (prepubertal) or around puberty (peripubertal) with a prototype commercial preparation and studied over the following 2 years to determine the long-term effects of such immunization on reproductive development, function and hormone concentrations. The treatment was equally effective in suppressing reproductive function and hormones when given at either time. Growth rates of immunized and controls rams were similar throughout the study. Prepubertal immunization delayed testicular growth until the rams were at least 27 weeks of age and some rams had subnormally sized testes even at 115 weeks of age. After peripubertal immunization, the mass of the testes declined and remained regressed until the rams were from 51 to 90 weeks old. There was a significant correlation between total testicular mass at 115 weeks of age and duration (weeks) of suppression of testicular growth (prepubertal, r = -0.7375; peripubertal, r = -0.7132, P < 0.001). Prepubertal immunization markedly delayed separation of the penis from the prepuce. The immunized rams did not display sexual activity until their total testicular mass reached at least 70 g. In control and immunized rams with testicular mass > 100 g, the semen did not differ in the percentage of spermatozoa that were unstained (live), of normal morphology, or showed progressive movement. Compared with the increase in plasma LH and FSH concentrations with age in control rams, the concentrations of these hormones in the immunized animals were lower and remained relatively constant from 46 to 90 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver biopsy as a technique for assessing copper status of sheep.

A procedure for taking biopsy samples from the ovine liver by a paracostal route is described. Samples were taken from 120 Merino rams on up to 3 occasions over a 3 month period. At the end of the period, the rams were subjected to 2 further biopsies and were then slaughtered, and the liver was removed and homogenised. Copper contents of all samples were determined. Frequency of biopsy did not affect hepatic copper concentration which was significantly overestimated by the biopsy method by approximately 5%. Variability associated with the biopsy procedure was approximately +/- 30 to 40 mg Cu/kg DM (SD) and was small relative to variability between animals. Experimental designs were preferred in which samples are taken before and after treatments are applied; changes in concentration are then analysed. Such analyses eliminate errors associated with variability between animals and the small bias in the sampling procedure. Liver biopsy did not significantly reduce bodyweight or the rate of gain.