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The objective of this study was to evaluate the analgesic properties of transdermal flunixin meglumine when given at the time of dehorning on pain biomarkers. Twenty-four weaned male Holstein calves, 6 to 8 wk of age were enrolled into the study. The calves were randomly assigned to 1 of 3 treatment groups: 1) transdermal flunixin and dehorn (DH-FLU); 2) transdermal flunixin and sham dehorn (SHAM-FLU); and 3) placebo and dehorn (DH-PLBO). Transdermal flunixin at a label dose of 3.33 mg/kg (or placebo at an equivalent volume) was administered as a pour-on along the top-line of the calves in each treatment group concurrently with electrocautery dehorning or sham dehorning. Biomarker parameters collected and analyzed included: infrared thermography (IRT), mechanical nociception threshold (MNT), plasma cortisol, and substance P (SP). There were no differences in maximal temperatures detected for the IRT measurements of the medial canthus of the eye for the DH groups. Mean control point MNT measurements at 48 h were 3.14 kgF, 3.46 kgF, and 1.43 kgF for the DH-FLU, Sham-FLU, and DH-PLBO groups, respectively (P = 0.0001). No other differences of MNT were detected between the dehorned groups for the other test sites and time points. Plasma cortisol reached peak concentration at 20 min postdehorning for the DH-FLU and DH-PLBO groups and 10 min for SHAM-FLU group. Peak plasma cortisol concentrations were 32.0 ng/mL, 12.7 ng/mL, and 28.8 ng/mL for the DH-FLU, SHAM-FLU, and DH-PLBO groups, respectively. Cortisol concentrations were lower for the DH-FLU group at 90 min postdehorning compared to the SHAM-FLU and DH-PLBO groups ( = 0.04). Area under the effect curve (AUEC) were similar for all groups ( = 0.93). No statistical differences in SP concentrations between groups were detected for any of the time points. In conclusion, transdermal flunixin meglumine given at the time of dehorning did not provide substantial analgesia based on the pain biomarkers investigated. Further investigation into its role as part of a multimodal analgesic plan is warranted.

Aquaculture is one of the largest growing sectors of the world food supply. There is evidence of pain perception in fish, but analgesic use in aquaculture is limited, as little information is available on the properties of analgesic drugs in fish. The objective was to investigate the comparative pharmacokinetics of flunixin administered intramuscularly and meloxicam administered intramuscularly or orally in tilapia. Two hundred-seventy fish were enrolled and assigned to 1 of 3 treatment groups 1) flunixin meglumine administered intramuscularly at a dose of 2.2 mg/kg; 2) meloxicam administered intramuscularly at a dose of 1 mg/kg; or 3) meloxicam administered orally at a dose of 1 mg/kg. Blood samples were collected from 6 fish per treatment group at 14 timepoints out to 10 days post-drug administration. Plasma drug concentrations were determined using ultra-high pressure liquid chromatography coupled with mass spectroscopy. The mean and standard error of the plasma concentration were calculated for each treatment at each timepoint. The plasma concentration versus time data were analyzed with a non-compartmental approach using a commercially available software (Phoenix®, Version 8.3, Certara, Inc., Princeton, NJ, USA). Flunixin reached a mean maximum concentration (Cmax) of 4826.7 ng/mL at 0.5 h, had a terminal half-life (T1/2) of 0.5h, and an area under the concentration time curve extrapolated to infinity (AUCINF_obs) of 25,261.62 h*ng/mL. Intramuscular meloxicam had a T1/2 of 9.4 h after reaching a Cmax of 11.3 ng/mL at 2 h, with an AUCINF_obs of 150.31 h*ng/mL. Oral meloxicam has a T1/2 of 1.9 h after reaching a Cmax of 72.2 ng/mL at 2 h, with an AUCINF_obs of 400.83 h*ng/mL. In conclusion, flunixin, when administered intramuscularly, reaches sufficient plasma concentrations to potentially have an effect, while meloxicam when administered intramuscularly or orally at the given dosage likely does not due to the relatively low plasma concentration.

Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P < 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a common physiological end point for each pen of calves. There were no differences among the experimental ANC observed during the finishing period (P ≥ 0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively impact clinical health and could potentially be detrimental to performance during the receiving period in high-risk calves receiving antimicrobial treatment for suspected BRD.

Pain associated with lameness on farm is a negative affective state and has a detrimental impact on individual farm animal welfare. Animal pain can be managed utilizing husbandry tools and through pharmacological approaches. Nonsteroidal anti-inflammatory drugs including meloxicam and flunixin meglumine are compounds used in many species for pain management because they are easy to administer, long lasting, and cost-effective. Assessing an animal's biomechanical parameters using such tools as the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system provides an objective, sensitive, and precise means to detect animals in lame states. The objectives of this study were to determine the efficacy of meloxicam and flunixin meglumine for pain mitigation in lame sows using the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system. Lameness was induced in 24 mature mixed-parity sows using a chemical synovitis model and compared 3 treatments: meloxicam (1.0 mg/kg per os), flunixin meglumine (2.2 mg/kg intramuscular) and sterile saline (intramuscular). Weight distribution (kg) for each foot was collected twice per second for a total of 5 min for each time point using the embedded microcomputer-based force plate system. Stride time, stride length, maximum pressure, activated sensors, and stance time were collected using 3 quality walks (readings) for each time point using the GAITFour pressure mat gait analysis walkway system. Sows administered flunixin meglumine or meloxicam tolerated more weight on their lame leg compared with saline sows (P < 0.005). Sows administered flunixin meglumine or meloxicam had smaller differences in stance time, maximum pressure, and activated sensors between the sound and lame legs compared with saline-treated sows between 37 and 60 h after lameness induction (P < 0.03). In conclusion, flunixin meglumine and meloxicam administration mitigated pain sensitivity in sows after lameness induction when pain sensitivity was evaluated with the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system. Analgesic drugs may be a key tool to manage negative pain affective states associated with lameness.

Hot-iron branding is painful for cattle, but little is known about the duration of or effective methods to control this pain. This work quantified pain sensitivity and healing in branded and unbranded animals. In addition, the effects of a single injection of nonsteroidal anti-inflammatory drug (NSAID) were also considered; this has been suggested as practical method of mitigating pain in the hours after the procedure. Calves (mean±SE, 126±2.2 d and 112±2.8 kg) were hot-iron branded and allocated to 1 of 4 treatments: branded with or without flunixin meglumine (intravenous; 1.1 mg/kg) and unbranded with or without this NSAID (n=12/treatment). Pain sensitivity was assessed by applying a known and increasing force with a von Frey anesthesiometer in the center of the brand (or equivalent area in nonbranded treatments) until animals showed a behavioral response. Healing was measured with a 6-point scale (1=fresh brand and 6=no scabbing and fully repigmented). These measures, along with weight gain and surface temperature, were recorded 1, 2, 7, 14, 21, 28, 35, 42, 56, and 71 d after branding. Lying behavior was recorded with loggers from the day before to d 27 after branding. Brand wounds were more painful than nonbranded tissue (P

Tail tip injuries occur in some feedlot cattle housed in slatted-floor facilities typically found in the midwestern United States. The practice of tail docking cattle on entry into these feedlot facilities was initiated to prevent tail injuries. Tail docking is a welfare concern from the standpoint that an important method of fly avoidance is removed and the tail docking procedure is painful and often excludes local anesthesia or extended analgesia. The primary objective of this study was to describe the behavioral responses of feedlot cattle following tail docking. Thirty-six heifers were randomly assigned to 1 of 2 treatment groups: docked (DK) or control (CN). All calves received an epidural following surgical preparation of the sacrococcygeal area and postoperative intravenous flunixin meglumine. A portion of the tail of DK calves was removed using pruning shears. An elastrator band was placed near the tail tip for hemostasis and tail tips were sprayed with fly spray. IceQube accelerometers collected step counts, motion index, lying time, lying bouts, and lying bout duration during d -4 through 13. Direct observations of cattle behavior were performed on d 0, 1, and 2. Step counts of DK calves were increased (P < 0.05) on d 0, 2, 3, 4, 6, 9, 10, and 13, and motion index of DK calves was also increased (P < 0.05) on d 0, 3, 4, 9, 10, 11, and 13. Docked cattle performed rear foot stomp behavior more (P < 0.001) than CN on d 0, 1, and 2. Forty-eight hours after tail docking, DK calves had increased lying bouts per hour (1.7 vs. 0.9 on d 0; P < 0.001; 1.1 vs. 0.8 on d 1; P < 0.01) but reduced lying bout durations (12.6 vs. 47.1 min on d 0; P < 0.001; 22.6 vs. 44.7 min on d 1; P < 0.001). On d 0, DK calves twitched tails more (P < 0.05) and ruminated less (P < 0.001). Despite provision of perioperative and postoperative analgesia, we identified altered behavior in DK cattle that may reflect a compromised welfare state for tail-docked feedlot cattle. We recommend that alternative strategies to reduce tail tip injury be explored.

The objective was to evaluate the effects of flunixin meglumine administration on physiological and performance responses of transported cattle during feedlot receiving. Forty-five Angus × Hereford steers were ranked by BW on d 0 and assigned to 1 of 3 treatments: 1) transport for 1,280 km in a commercial livestock trailer and administration of flunixin meglumine (1.1 mg/kg BW; intravenous) at loading (d 0) and unloading (d 1; FM), 2) transport for 1,280 km in a commercial livestock trailer and administration of 0.9% saline (0.022 mL/kg BW; intravenous) at loading (d 0) and unloading (d 1; TRANS), or 3) no transport and administration of 0.9% saline (0.022 mL/kg BW; intravenous) concurrently with loading (d 0) and unloading (d 1) of FM and TRANS cohorts (CON). Upon arrival and processing for treatment administration on d 1, steers within each treatment were ranked by BW and assigned to 15 feedlot pens (5 pens/treatment, 3 steers/pen). Full BW was recorded before (d -1 and 0) treatment application and at the end of experiment (d 28 and 29) for ADG calculation. Total DMI was evaluated daily from d 1 to 28. Blood samples were collected on d 0 (before treatment administration), 1 (after unloading but before treatment administration), 4, 7, 10, 14, 21, and 28. Body weight shrink from d 0 to 1 was less (P

Pregnancy loss in beef cattle after d 28 of gestation is variable, but it has been reported to be as great as 14% and has been related to transportation or handling stress. The primary objective of this study was to determine whether activation of the hypophyseal-adrenal axis with ACTH would mimic a stressful response and cause pregnancy loss in beef cattle. A secondary objective was to determine if a single injection of the PG synthesis inhibitor flunixin meglumine would attenuate the stress response and suppress serum PGF(2α) concentrations to prevent pregnancy loss. Forty nonlactating beef cows that were 34 ± 0.33 d pregnant were used for this study. In a 2 × 3 factorial arrangement, cows were randomly assigned to receive ACTH [0 or 0.5 IU/kg of BW, intramuscularly (i.m.)] at 0 and 2 h of the study and flunixin meglumine (0, 1.1, or 2.2 mg/kg of BW, i.m.) at 0 h. Blood samples were collected from all cows at 0 h and every 30 min for 4 h to measure serum cortisol and PGF(2α) metabolite (PGFM) concentrations. Rectal temperature was collected for each cow at 0, 120, and 240 min. Pregnancy exams were conducted 31 and 58 d after treatment by transrectal ultrasonography, and the presence of a fetal heartbeat was used as an indicator of fetal viability. Serum cortisol concentration was affected (P 0.35) with ACTH, but was affected (P < 0.01) by flunixin meglumine, time, and the interaction of flunixin meglumine × time. Regardless of dosage (1.1 or 2.2 mg/kg of BW), flunixin meglumine decreased (P < 0.01) serum PGFM concentrations in both ACTH-treated and control cows for the duration of the study. Although ACTH treatment induced a prolonged increase in serum cortisol concentration, none of the cows used in this study lost a pregnancy. In conclusion, the activation of the hypophyseal-adrenal axis with ACTH increased serum cortisol concentrations but did not increase serum concentrations of PGFM or cause pregnancy loss during early gestation in cows. Flunixin meglumine treatment suppressed serum PGFM concentrations in control and ACTH-treated cows.

The objective of this research was to determine effects of a single injection of the PG synthesis inhibitor flunixin meglumine (FM; 1.1 mg/kg of BW, intramuscularly) approximately 13 d (range 10 to 15 d) after AI on pregnancy establishment. Three experiments were conducted using estrus-synchronized heifers and cows. Technicians and AI sires were equally represented across treatments within locations and experiments. Bulls were introduced on the day of FM treatment. Pregnancy to AI was diagnosed 28 to 50 d after AI using ultrasonography. In Exp. 1, beef heifers (n = 1,221) were divided within 5 locations to receive FM or no further treatment (control). At insemination, heifers were divided into 2 similar pastures or pens, and approximately 13 d later, 1 group of heifers within each location was processed through an animal handling facility to administer FM treatment. There was no location x treatment interaction (P = 0.62) on AI pregnancy rates, so data were pooled. Pregnancy rates to AI were reduced (P = 0.02) among heifers receiving the FM treatment procedure (66%) compared with control heifers (72%). In Exp. 2, suckled beef cows (n = 719) were assigned within 2 locations to receive FM or no further treatment (control) approximately 13 d after AI. At insemination, control and FM cows were divided into separate pastures, and only FM cows were handled after AI for the FM treatment procedure. There was no location x treatment interaction (P = 0.75), so data were pooled. Pregnancy rates to AI did not differ (P = 0.80) between FM (57%) and control cows (59%). In Exp 3, beef heifers (n = 247) and suckled beef cows (n = 335) from 1 location received no injection (control) or injection of FM approximately 13 d after AI when all cows and heifers were processed through a working facility. Pregnancy rates to AI were not different (P = 0.37) between FM (45%) and control (42%) cows or between FM (56%) and control (55%) heifers. We conclude FM administration at 1.1 mg/kg of BW approximately 13 d after AI did not improve pregnancy establishment in beef cows and heifers and that the effects of handling heifers at this time may decrease pregnancy establishment.

Objectives of these studies were to determine the effects of flunixin meglumine (FM) administration on early embryonic mortality and circulating PG and cortisol concentrations in transported and non-transported cows. Cows (n = 483) from 3 locations were used to evaluate the effects of transportation and FM approximately 14 d after AI on the establishment of pregnancy and serum concentrations of progesterone, PGF metabolite (PGFM), and cortisol. Treatments were transport (n = 129), transport + FM (n = 128), no transport (n = 130), and no transport + FM (n = 96). Multiparous cows (n = 224) were used at 2 locations, and nulliparous cows (n = 259) were used at 1 location. The no transport + FM treatment was used at only 2 locations. Flunixin meglumine (approximately 1.1 mg/kg of BW; i.m.) was administered before the cows were separated into transportation groups. Transportation included 4 to 6 h of transportation, without calves, via semitractor trailer. Nontransported cows remained penned, with their calves in adjacent pens, during the same period as the transported cows. Blood samples were collected from all cows before and after treatment and, at 2 locations, approximately 3 h after the onset of treatment. Location affected AI pregnancy rate (P < 0.01). Treatment effects, although not significant (P = 0.16), were of a magnitude to be considered practically important. Cows that received transportation + FM tended (P = 0.07) to have greater AI pregnancy rates (74%) than those that did not receive FM (66%), irrespective of transportation. Cortisol concentration was greater (P < 0.05) for transported cows than for nontransported cows. Cows receiving FM had greater (P < 0.05) AI pregnancy rates than non-FM cows (71 vs. 61%, respectively). Cows receiving transportation had lower (P < 0.01) mean PGFM concentrations than nontransported cows (45.4 vs. 54.6 pg/mL, respectively), and cows receiving FM had lower (P < 0.01) mean PGFM concentrations than non-FM cows (39.4 vs. 60.6, respectively). We conclude that transportation of cows approximately 14 d after AI increased serum cortisol concentrations but did not affect AI pregnancy rates. However, treatment of cows with FM increased AI pregnancy rates, irrespective of whether they were transported.