Unmitigated Surgical Castration in Calves of Different Ages: Cortisol Concentrations, Heart Rate Variability, and Infrared Thermography Findings.

The objective was to characterize physiological responses to unmitigated surgical castration in calves of varying ages. Thirty male Holstein calves of three ages [<6 w (6W); 3 m (3M); 6 m (6M); n = 10] underwent a simulated castration treatment (SHAM) followed 24 h later by castration (CAST). For both treatments, heart rate variability, eye temperature, and cortisol were measured over time from treatment to specified end points to capture the acute response period. Interactions between treatment and age (p = 0.035) and time and age (p < 0.001) were noted for cortisol. The 6W calves had lower cortisol compared to 6M calves at SHAM and CAST. Cortisol of 6W calves decreased from peak to pre-treatment levels faster than 6M calves. An interaction between time and age was reported in squared differences of inter-beat-intervals (RMSSD; p = 0.02) and high-frequency power (HFP; p = 0.05), whereby both responses decreased in 6W calves during the sampling period which was not seen in 3M and 6M calves. Average eye temperature (AET) differed by age (p = 0.0018) whereby 6W calves had lower AET than 6M calves (p = 0.0013) regardless of treatment and time. The findings suggest that responses to unmitigated surgical castration seem to be mediated by the autonomic nervous system in an age-related manner.

Unmitigated Surgical Castration in Calves of Different Ages: Electroencephalographic and Neurohormonal Findings.

Castration is a common management procedure employed in North American cattle production and is known to cause a pain response. The present study was designed to investigate the effect of unmitigated surgical castration on the electroencephalography (EEG) responses and plasma substance P (SP) concentrations in calves of different ages under the same experimental conditions. Thirty male Holstein calves in three age categories [<6 weeks (6W); 3 months (3M); 6 months (6M); 10 calves per age group] were used in the study. Calves were subjected to a simulated castration session (SHAM) followed 24 h later by surgical castration (CAST) without analgesia. An EEG analysis was performed before the procedure (i.e., baseline), at treatment, and 0-5, 5-10, and 10-20 min post-treatment for both SHAM and CAST, respectively. Blood samples were collected immediately prior to both treatments (time 0) and again at 1, 2, 4, 8, and 12 h after both treatments. The EEG results showed a three-way interaction between treatment, age, and time for delta and beta absolute power, beta relative power, total power, and median frequency (p = 0.004, p = 0.04, p = 0.04, p = 0.03, and p = 0.008, respectively). Following CAST, EEG total power decreased, and median frequency increased relative to SHAM in 6W and 3M calves only following treatment. For 6W and 3M calves, delta and beta absolute power increased at CAST and at later time points relative to SHAM. Marginal evidence for two-way interactions was noted between time and treatment and between age and treatment on the concentration of SP (p = 0.068 and p = 0.066, respectively). Substance P concentrations decreased in CAST treatment compared to SHAM at the later times (8 h: p = 0.007; 12 h: p = 0.048); 6W calves showed lower SP concentration at CAST relative to SHAM (p = 0.017). These findings indicate variation in EEG responses and in SP concentrations following unmitigated surgical castration in calves and that these responses may be age specific. These EEG findings have implications for supporting the perception of the pain associated with surgical castration in young calves and emphasize the urgency of pain mitigation strategies during routine husbandry practices such as castration, as typically implemented in North American cattle management.

Effects of sample handling methods on substance P concentrations and immunoreactivity in bovine blood samples.

OBJECTIVE: To determine the effects of protease inhibitors and holding times and temperatures before processing on the stability of substance P in bovine blood samples. SAMPLES: Blood samples obtained from a healthy 6-month-old calf. PROCEDURES: Blood samples were dispensed into tubes containing exogenous substance P and 1 of 6 degradative enzyme inhibitor treatments: heparin, EDTA, EDTA with 1 of 2 concentrations of aprotinin, or EDTA with 1 of 2 concentrations of a commercially available protease inhibitor cocktail. Plasma was harvested immediately following collection or after 1, 3, 6, 12, or 24 hours of holding at ambient (20.3° to 25.4°C) or ice bath temperatures. Total substance P immunoreactivity was determined with an ELISA; concentrations of the substance P parent molecule, a metabolite composed of the 9 terminal amino acids, and a metabolite composed of the 5 terminal amino acids were determined with liquid chromatography-tandem mass spectrometry. RESULTS: Regarding blood samples processed immediately, no significant differences in substance P concentrations or immunoreactivity were detected among enzyme inhibitor treatments. In blood samples processed at 1 hour of holding, substance P parent molecule concentration was significantly lower for ambient temperature versus ice bath temperature holding conditions; aprotinin was the most effective inhibitor of substance P degradation at the ice bath temperature. The ELISA substance P immunoreactivity was typically lower for blood samples with heparin versus samples with other inhibitors processed at 1 hour of holding in either temperature condition. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that blood samples should be chilled and plasma harvested within 1 hour after collection to prevent substance P degradation.

Pharmacokinetics and effect of intravenous meloxicam in weaned Holstein calves following scoop dehorning without local anesthesia.

BACKGROUND: Dehorning is a common practice involving calves on dairy operations in the United States. However, less than 20% of producers report using analgesics or anesthetics during dehorning. Administration of a systemic analgesic drug at the time of dehorning may be attractive to dairy producers since cornual nerve blocks require 10 - 15 min to take effect and only provide pain relief for a few hours. The primary objectives of this trial were to (1) describe the compartmental pharmacokinetics of meloxicam in calves after IV administration at 0.5 mg/kg and (2) to determine the effect of meloxicam (n = 6) or placebo (n = 6) treatment on serum cortisol response, plasma substance P (SP) concentrations, heart rate (HR), activity and weight gain in calves after scoop dehorning and thermocautery without local anesthesia. RESULTS: Plasma meloxicam concentrations were detectable for 50 h post-administration and fit a 2-compartment model with a rapid distribution phase (mean T(1/2α) = 0.22 ± 0.087 h) and a slower elimination phase (mean T(1/2ß) = 21.86 ± 3.03 h). Dehorning caused a significant increase in serum cortisol concentrations and HR (P < 0.05). HR was significantly lower in the meloxicam-treated calves compared with placebo-treated calves at 8 h (P = 0.039) and 10 h (P = 0.044) after dehorning. Mean plasma SP concentrations were lower in meloxicam treated calves (71.36 ± 20.84 pg/mL) compared with control calves (114.70 ± 20.84 pg/mL) (P = 0.038). Furthermore, the change in plasma SP from baseline was inversely proportional to corresponding plasma meloxicam concentrations (P = 0.008). The effect of dehorning on lying behavior was less significant in meloxicam-treated calves (p = 0.40) compared to the placebo-treated calves (P < 0.01). Calves receiving meloxicam prior to dehorning gained on average 1.05 ± 0.13 kg bodyweight/day over 10 days post-dehorning compared with 0.40 ± 0.25 kg bodyweight/day in the placebo-treated calves (p = 0.042). CONCLUSIONS: To our knowledge, this is the first published report examining the effects of meloxicam without local anesthesia on SP, activity and performance of calves post-dehorning. These findings suggest that administration of meloxicam alone immediately prior to dehorning does not mitigate signs of acute distress but may have long term physiological, behavior and performance effects.

Assessment of behavioral changes associated with oral meloxicam administration at time of dehorning in calves using a remote triangulation device and accelerometers.

BACKGROUND: Dehorning is common in the cattle industry, and there is a need for research evaluating pain mitigation techniques. The objective of this study was to determine the effects of oral meloxicam, a non-steroidal anti-inflammatory, on cattle behavior post-dehorning by monitoring the percent of time spent standing, walking, and lying in specific locations within the pen using accelerometers and a remote triangulation device. Twelve calves approximately ten weeks of age were randomized into 2 treatment groups (meloxicam or control) in a complete block design by body weight. Six calves were orally administered 0.5 mg/kg meloxicam at the time of dehorning and six calves served as negative controls. All calves were dehorned using thermocautery and behavior of each calf was continuously monitored for 7 days after dehorning using accelerometers and a remote triangulation device. Accelerometers monitored lying behavior and the remote triangulation device was used to monitor each calf's movement within the pen. RESULTS: Analysis of behavioral data revealed significant interactions between treatment (meloxicam vs. control) and the number of days post dehorning. Calves that received meloxicam spent more time at the grain bunk on trial days 2 and 6 post-dehorning; spent more time lying down on days 1, 2, 3, and 4; and less time at the hay feeder on days 0 and 1 compared to the control group. Meloxicam calves tended to walk more at the beginning and end of the trial compared to the control group. By day 5, the meloxicam and control group exhibited similar behaviors. CONCLUSIONS: The noted behavioral changes provide evidence of differences associated with meloxicam administration. More studies need to be performed to evaluate the relationship of behavior monitoring and post-operative pain. To our knowledge this is the first published report demonstrating behavioral changes following dehorning using a remote triangulation device in conjunction with accelerometers.

Pharmacokinetics of oral gabapentin alone or co-administered with meloxicam in ruminant beef calves.

Gabapentin is a γ-aminobutyric acid (GABA) analogue indicated for treatment of neuropathic pain. This study determined the pharmacokinetics of oral (PO) gabapentin alone or in combination with meloxicam in ruminant calves. Gabapentin capsules at 10mg/kg or gabapentin powder (from capsules at 15mg/kg) and meloxicam tablets (0.5mg/kg) were administered PO to six beef calves. Plasma drug concentrations were determined over 48h post-administration by liquid chromatography/mass spectrometry followed by non-compartmental pharmacokinetic analysis. The mean (± standard deviation, SD) C(max), T(max) and elimination half-life (t(½)λz) for gabapentin (10mg/kg) alone was 2.97 ± 0.40µg/mL, 9.33 ± 2.73h and 11.02 ± 3.68h, respectively. The mean (± SD) C(max), T(max) and t(½)λz for gabapentin (15mg/kg) co-administered with meloxicam was 3.57±1.04µg/mL, 7.33 ± 1.63h and 8.12±2.11h, respectively. The mean (±SD) C(max), T(max) and t(½)λz for meloxicam was 2.11± 0.19µg/mL, 11.67 ± 3.44h and 20.47 ± 9.22h, respectively. Plasma gabapentin concentrations >2µg/mL were maintained for up to 15h and meloxicam concentrations >0.2µg/mL for up to 48h. The pharmacokinetic profile of oral gabapentin and meloxicam supported clinical evaluation of these compounds for management of neuropathic pain in cattle.

Pharmacokinetics of intravenous and oral meloxicam in ruminant calves.

The purpose of this study was to investigate the pharmacokinetics and oral bioavailability of meloxicam in ruminant calves. Six Holstein calves (145 to 170 kg) received meloxicam at 0.5 mg/kg IV or 1 mg/kg PO in a randomized crossover design with a 10-day washout period. Plasma samples collected up to 96 hours after administration were analyzed by liquid chromatography/mass spectrometry followed by noncompartmental pharmacokinetic analysis. A mean peak plasma concentration of 3.10 microg/ml (range, 2.64 to 3.79 microg/ml) was recorded at 11.64 hours (range, 10 to 12 hours) with a half-life of 27.54 hours (range, 19.97 to 43.29 hours) after oral meloxicam administration. The bioavailability of oral meloxicam corrected for dose was 1.00 (range, 0.64 to 1.66). These findings indicate that oral meloxicam administration might be an effective and convenient means of providing long-lasting analgesia to ruminant calves.