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Journal of Animal Science - Animal Production

Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls123

 

This article in JAS

  1. Vol. 93 No. 8, p. 4123-4131
     
    Received: Mar 31, 2015
    Accepted: June 15, 2015
    Published: July 24, 2015


    4 Corresponding author(s): jricheson@wtamu.edu
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doi:10.2527/jas.2015-9160
  1. S. L. Roberts*,
  2. H. D. Hughes*,
  3. N. C. Burdick Sanchez,
  4. J. A. Carroll,
  5. J. G. Powell,
  6. D. S. Hubbell§ and
  7. J. T. Richeson 4*
  1. * Department of Agricultural Sciences, West Texas A&M University, Canyon 79016
     Livestock Issues Research Unit, USDA-ARS, Lubbock, TX 79403
     Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville 72701
    § Livestock and Forestry Research Station, Division of Agriculture, University of Arkansas, Batesville 72501

Abstract

Pain management and welfare are increasingly prevalent concerns within animal agriculture. Analgesics may alleviate pain and inflammation associated with castration of beef cattle. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whether concurrent oral administration of meloxicam (1 mg/kg BW) would alter these responses. On d –1, crossbred bull calves (n = 30; initial BW = 227.4 ± 10.3 kg) were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices, placed into individual stanchions, and randomly assigned to 1 of 3 treatments. Treatment application occurred at h 0 and consisted of 1) intact bull calves treated with sham castration (CON), 2) bulls surgically castrated without meloxicam administration (CAS), and 3) bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL). Blood samples were collected at 0.5-h intervals from h –2 to 4, 1.0-h intervals from h 4 to 8, and 12-h intervals from h 12 to 72. Serum was analyzed for cortisol and haptoglobin (Hp) concentrations using ELISA. Whole blood was analyzed for complete blood counts at –2, 0, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 h, and RT was recorded in 5-min intervals. Postcastration RT was greatest for MEL (39.04), intermediate for CAS (38.99), and least for CON (38.93°C; P ≤ 0.01). Serum cortisol was increased (P < 0.001) for CAS (12.3) and MEL (11.3) compared with CON (6.7 ng/mL) during the postcastration period. At 0.5 and 1.5 h, cortisol concentration was greater in CAS and MEL than CON, whereas at 2 and 2.5 h, cortisol concentration was greatest for CAS, intermediate for MEL, and least for CON (treatment × time, P < 0.001). Total white blood cell (P ≤ 0.04), lymphocyte (P ≤ 0.02), and monocyte (P ≤ 0.002) counts were greatest for CAS, intermediate for MEL, and least for CON. Administration of MEL reduced (P ≤ 0.002) eosinophil counts during the postcastration period when compared with CON and CAS. The change in serum Hp, relative to baseline values, was reduced for MEL at 36 (P < 0.01) and 60 h (P ≤ 0.03), and the overall Hp concentration was least for MEL (P < 0.001). Oral administration of meloxicam at the time of castration reduced the acute inflammatory response in castrates, as evidenced by a reduction in Hp and certain leukocyte concentrations; it also caused a delayed increase in RT. Further research is needed to determine if this reduced acute inflammatory response would equate to improved health and/or performance after castration.



INTRODUCTION

Castration in beef bulls is a painful and stressful yet common management practice within the United States. Physical castration methods are known to have adverse effects such as transiently reduced gain performance (Faulkner et al., 1992; Fisher et al., 1996) or increased bovine respiratory disease risk (Richeson et al., 2013) and result in both physiological and behavioral changes that suggest pain. Pain is difficult to assess in farm animals; however, some biomarkers that can be used as a proxy for pain include changes in cortisol, white blood cells, substance P, and/or acute phase proteins (Molony et al., 1995).

The American Association of Bovine Practitioners recommends that long-lasting nonsteroidal anti-inflammatory drugs (NSAID) be used to extend the postoperative period analgesia (AABP, 2014). Pain management strategies could be implemented to help mitigate the negative effects associated with castration, but extensive research is needed to establish their efficacy and potential for adverse effects. Currently, there are no NSAID approved by the U.S. Food and Drug Administration for analgesic use in cattle. Meloxicam is a NSAID that is approved for pain management in companion animals, and under the guide of the Animal Medicinal Drug Use Clarification Act, meloxicam can be prescribed by a veterinarian to reduce pain in recently castrated beef calves (Coetzee, 2011). Meloxicam is known to preferentially bind to cyclooxygenase-2 (COX-2) receptors within the peripheral tissue. Inhibition of COX-2 receptors reduces the synthesis of inflammatory PG, primarily PGE, from arachidonic acid (Ochroch et al., 2003). Therefore, we hypothesized that oral administration of meloxicam would mitigate pain by reducing inflammation following surgical castration of yearling beef bulls. The objective of this study was to elucidate the effect of surgical castration on the acute inflammatory response and immunomodulation and determine if concurrent oral administration of meloxicam would alter these responses.


MATERIALS AND METHODS

This study was conducted during June 2013 at the USDA-ARS Livestock Issues Research Unit near Lubbock, TX. All animals were cared for in accordance to the acceptable practices and experimental protocols approved by the West Texas A&M University (WTAMU; protocol number 04-05-13) and USDA-ARS Livestock Issues Research Unit Animal Care and Use Committees (protocol number 2013-04-JTR01).

Animals

Thirty clinically healthy, crossbred beef bulls from the University of Arkansas Livestock and Forestry Research Station near Batesville, AR, were used for this study. Following weaning, animals were preconditioned on the ranch of origin for 42 d before being transported approximately 1,233 km to the WTAMU Nance Ranch (Canyon, TX). After a 7-d rest period, cattle were then transported approximately 177 km to the USDA-ARS Bovine Immunology Research and Development facility (Lubbock, TX) where the study was conducted. Average BW at the start of the study was 227.4 ± 10.3 kg. On d –1, an indwelling jugular vein catheter was placed into all animals to facilitate intensive, serial blood collection. Animals were also fitted with an indwelling rectal temperature (RT) monitoring device described previously by Burdick et al. (2012). Animals were housed in individual stanchions for the duration of the 3-d study. Once animals were placed in their assigned stanchion, a 24-h acclimation period was allotted before castration was performed to mitigate stress experienced from acclimation to the stanchions and jugular catheterization procedure.

Treatments

On d –1, animals were ranked by BW and randomly assigned to 1 of 3 castration treatments: 1) intact bull calves treated with sham castration (CON) to serve as a positive control (n = 10), 2) bulls surgically castrated without meloxicam administration (CAS; n = 10), and 3) bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL; n = 10). Treatment randomization was achieved by drawing cards from a hat with the number 1, 2, or 3 that corresponded to treatment number; the cards were replaced and redrawn and treatments were assigned according to BW stratification. Meloxicam tablets (Carlsbad Technology, Inc., Carlsbad, CA) were pulverized, placed into gelatin capsules, and administered with a bolus device. Individual animal dosage was determined using the d –1 BW. The boluses containing meloxicam were administered directly into the rumen via esophageal intubation. Administration of meloxicam was concurrent with the castration procedure and was not repeated to mimic practical industry use, yet Van Engen et al. (2014) suggested that oral administration of meloxicam at 1 mg/kg provides circulating meloxicam concentration for up to 5 d.

Castration was performed in the stanchions using a rope to restrain a hind leg, and then the ventral one-third of the scrotum was removed with a scalpel and the testes were pulled ventrally exposing the spermatic cords, which were then severed with a scalpel using aseptic technique. Aseptic technique included rinsing gloved hands in an antiseptic bath and changing scalpel blades between each animal. An antiseptic spray solution (Wound-Kote Spray; Farnam Inc., Phoenix, AZ) was also applied to the surgical site immediately following the castration procedure. However, to mimic practical industry use, the surgical site was not prepared before castration and local anesthetic was not administered. To account for the influence of handling stress from castration, the CON calves were subjected to a sham castration procedure. Sham castration was performed by administering an empty gelatin bolus and these animals had their hind leg restrained for 2 min to impose the stress involved in handling the animals for the surgical castration procedure.

Blood Collection and Analysis

Blood was collected via jugular catheter every 30 min from –2 to 4 h, hourly from 4 to 8 h, and every 12 h from 12 to 72 h relative to castration (h 0). Blood was collected into 2 commercial blood collection tubes. A sampling tube without an additive (Sarstedt, Inc., Newton, NC) was used to collect blood used to harvest serum, which was stored in triplicate aliquots at –80°C after centrifugation at 1,500 × g for 20 min at 4°C. For complete blood count (CBC) analysis, whole blood was collected at h –2, 0, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 into 4-mL evacuated tubes with 7.2 mg K2 EDTA (Vacutainer; Becton, Dickinson and Company, Franklin Lakes, NJ) and CBC analysis was performed within 30 min following blood collection using an automated hemocytometer (ProCyte DX Hematology Analyzer; IDEXX Laboratories, Westbrook, ME). Rectal temperature was recorded by the indwelling device every 5 min from d –1 to 3 and then averaged to hourly intervals for statistical analysis.

Haptoglobin (Hp) concentration was determined from sera at the WTAMU Ruminant Health and Immunology Laboratory (Canyon, TX]) using a commercial, bovine-specific sandwich ELISA kit (Immunology Consultant Laboratory, Inc., Portland, OR). The Hp analysis had intra- and interassay CV of 11.6 and 15.2%, respectively. Serum cortisol (Arbor Assays, Ann Arbor, MI) and proinflammatory cytokines (SearchLight; Aushon Biosystems Inc., Billerica, MA) were analyzed at the USDA-ARS Livestock Issues Research Unit laboratory using ELISA assays. Serum cortisol had intra- and interassay CV of 9.2 and 15.2%, respectively. The cytokine assays intra- and interassay CV were ≤6.7 and ≤18.1%, respectively.

Statistical Analysis

For all dependent variables, the MIXED procedure with repeated measures (SAS Inst., Inc., Cary, NC) was used to analyze data. The model included the main effects of treatment, time, and treatment × time with individual animal serving as the subject. The repeated statement was time (h) and the covariance structure with the lowest Akaike information criterion for each dependent variable was used. Data were tested for normal distribution using PROC UNIVARIATE and nonparametric data was log2–transformed if normality was improved. Differences of least squares means were determined using the PDIFF option in SAS. Variables from h –2 to 0 were averaged and used as the baseline covariate for data that depict change relative to baseline values. Effects of treatment, time, and their interaction were determined to be statistically significant at P ≤ 0.05 with 0.05 < P ≤ 0.10 considered a tendency.


RESULTS

A treatment × time interaction was detected (P < 0.001) for serum cortisol concentration (Fig. 1). No treatment differences (P = 0.15) were detected before castration was performed. Immediately following castration (h 0.5), cortisol concentrations were markedly elevated (P ≤ 0.05) in both castrated groups (24.13 and 26.27 ng/mL for CAS and MEL, respectively) compared with the CON group (13.88 ng/mL). At h 2 and 2.5, all treatments differed (P ≤ 0.02), with cortisol concentration being greatest for CAS, intermediate for MEL, and least for CON. At h 3, CAS had the greatest (P ≤ 0.02) cortisol concentration compared with CON and MEL, whereas MEL was greater than CON (P = 0.05). At h 4, cortisol concentration was reduced (P ≤ 0.05) for CON compared with CAS and MEL, with no differences (P = 0.44) between the 2 castrated groups. Likewise, cortisol concentration was increased (P = 0.03) in castrates compared with CON at h 6.

Figure 1.
Figure 1.

Serum cortisol concentration (±SEM) of intact bull calves treated with sham castration (CON; n = 10), bulls surgically castrated without meloxicam administration (CAS; n = 10), and bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL; n = 10). A treatment × time interaction was detected (P < 0.001). Within hour, letters indicate the following mean comparisons (P ≤ 0.05): a = CON vs. CAS, b = CON vs. MEL, and c = CAS vs. MEL.

 

There was no treatment × time interaction (P = 0.38) for postcastration serum Hp concentration; however, there was a treatment effect (P < 0.001; data not shown) detected, with CAS having the greatest Hp concentrations, CON having intermediate concentrations, and MEL having the least concentrations of Hp. Baseline values (h –2 to 0) were used as a covariate (P = 0.14) to determine the change in serum Hp concentrations, which resulted in a tendency (P = 0.07) for a treatment × time interaction (Fig. 2). The CAS treatment had a greater change (P = 0.05) in Hp at h 7, with MEL having the least and the change in CON being intermediate; this pattern was relatively maintained through h 24. At h 36, the CON group had the greatest (P < 0.01) change in Hp concentration with the CAS group being intermediate and the MEL group having the least change compared with baseline values.

Figure 2.
Figure 2.

Change in serum haptoglobin concentration (±SEM) of intact bull calves treated with sham castration (CON; n = 10), bulls surgically castrated without meloxicam administration (CAS; n = 10), and bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL; n = 10). Values collected before castration (h –2 to –0.5) were used as the covariate (P = 0.137). A tendency for a treatment × time interaction was detected (P = 0.074). Within hour, letters indicate the following mean comparisons (P ≤ 0.05): a = CON vs. CAS, b = CON vs. MEL, and c = CAS vs. MEL.

 

The change in RT (Fig. 3) is reported due to unexplained treatment differences observed (P = 0.01) before castration. Baseline RT values were used as a covariate (P < 0.001) in this analysis. There was no treatment × time interaction (P = 0.84); however, there was an effect of both treatment (P < 0.001) and time (P < 0.001). The MEL group exhibited a greater RT compared with both the CON and CAS groups.

Figure 3.
Figure 3.

Change in rectal temperature of intact bull calves treated with sham castration (CON; n = 10), bulls surgically castrated without meloxicam administration (CAS; n = 10), and bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL; n = 10). Values recorded before castration (h –2 to –0.5) were used as the covariate (P < 0.001). No treatment × time interaction was detected (P = 0.84); however, there was a significant treatment (P < 0.001) and time (P < 0.001) effect.

 

No treatment × time interaction (P = 0.19) was detected for total white blood cells (WBC); however, there was a postcastration treatment effect (P < 0.001), with CAS having the greatest number of WBC and MEL and CON having the least WBC concentrations (Fig. 4). There was a difference (P < 0.001) in postcastration neutrophil concentrations (Fig. 4), with the MEL group having a decreased concentration as compared with the CON and CAS groups. A postcastration treatment × time interaction (P = 0.02) was detected for blood lymphocyte concentration (Fig. 5). Control calves had a decreased (P ≤ 0.02) number of circulating lymphocytes compared with the CAS and MEL calves from h 4 to 8. A treatment difference was detected (P < 0.001) in postcastration monocyte concentration, with CAS having the greatest concentration, CON the least, and MEL being intermediate (Fig. 4). A difference (P < 0.001) was also detected for blood eosinophil concentration. The CON group had the greatest eosinophil concentration, the MEL group had the least, and the CAS group was intermediate (Fig. 4). There was a postcastration treatment effect on red blood cells (P < 0.001) that followed the eosinophil trend, with the CON group having the greatest concentration and the CAS and MEL groups having the least concentrations (Fig. 6). Platelets had a postcastration treatment effect (Fig. 6; P = 0.008), with CON having the greatest values of this variable, and there was no difference between the castrated groups. Hematocrit (Fig. 6; P < 0.001) was affected similar to platelets; the CON group (10.87 g/dL) was greatest with no difference between the CAS (10.22) and MEL (10.11 g/dL) groups. No differences (P ≥ 0.16) in neutrophil:lymphocyte or basophil concentrations were detected in this study (data not shown).

Figure 4.
Figure 4.

Postcastration (h 0.5 to 72) white blood cell, eosinophil, neutrophil, and monocyte concentrations (±SEM) of intact bull calves treated with sham castration (CON; n = 10), bulls surgically castrated without meloxicam administration (CAS; n = 10), and bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL; n = 10). Treatment effect (P ≤ 0.001); a–cmeans with different letters differ (P ≤ 0.002).

 
Figure 5.
Figure 5.

Blood lymphocyte concentration (±SEM) of intact bull calves treated with sham castration (CON; n = 10), bulls surgically castrated without meloxicam administration (CAS; n = 10), and bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL; n = 10). A treatment × time interaction was detected (P = 0.016). Within hour, letters indicate the following comparison (P ≤ 0.02): a = CON vs. CAS, b = CON vs. MEL, and c = CAS vs. MEL.

 
Figure 6.
Figure 6.

Postcastration (h 0.5 to 72) red blood cell, platelets and hematocrit concentrations ( ± SEM) of intact bull calves treated with sham castration (CON; n = 10), bulls surgically castrated without meloxicam administration (CAS; n = 10), and bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL; n = 10). Treatment effect (P ≤ 0.008); a–cmeans with different letters differ (P ≤ 0.002).

 

There was no treatment × time interaction (P = 0.78) observed for tumor necrosis factor-α (TNF-α); however, pre- (P < 0.001) and postcastration (P < 0.001) treatment effects were observed. The CAS group had the least TNF-α concentration both before (P ≤ 0.05) and after castration (P < 0.001). Precastration concentration indicated that the CON group had a greater TNF-α concentration compared with the MEL group; however, postcastration TNF-α was not different between the CON and MEL groups (data not shown). Due to interferon-γ (IFN-γ) treatment differences (P = 0.04) before castration, baseline IFN-γ concentrations were used as a covariate (P < 0.001) to show the change in IFN-γ. There was no treatment × time interaction for change in IFN-γ (P = 0.77), but there was a treatment effect (P = 0.01; data not shown). The CAS group had the greatest change in IFN-γ and the MEL group had the least change whereas the CON group did not differ (P ≥ 0.06) from either of the other 2 treatment groups. There was a postcastration treatment effect (P = 0.04; data not shown) observed for IL-6. The CON group had the greatest concentration, the CAS group had the least, and the MEL group was intermediate.

The metabolic variables measured in this study were glucose and NEFA. There was no treatment × time interaction (P = 0.94) observed for glucose; however, there was a postcastration treatment difference (P < 0.001). No difference in glucose was observed between the CAS (186.92 mg/dL) and MEL (182.76 mg/dL) groups; however, glucose concentration was reduced for the CON group (173.05 mg/dL). There were no differences (P = 0.32) observed in NEFA concentrations throughout this study (data not shown).


DISCUSSION

Castration of beef cattle is known to be a painful and stressful event that stimulates the hypothalamic–pituitary–adrenal axis resulting in synthesis and secretion of the glucocorticoid cortisol (Minton, 1994). Furthermore, immunomodulation such as alterations in total WBC concentration (Chase et al., 1995) and increases in acute phase proteins (APP; Brown et al., 2015) have been observed following castration of beef cattle. The negative perception associated with pain caused by castration and other management practices is a growing concern making the development of strategies to control pain an important area of research. Molony and Kent (1997) defined pain as “an aversive feeling or sensation associated with actual or potential tissue damage resulting in physiological, neuroendocrine and behavioral changes that indicate a stress response.” Two distinct categories of pain associated with surgical castration are plausible: 1) the initial, acute pain associated with the incision and 2) the prolonged pain due to the inflammatory response. Meloxicam is classified as a NSAID, which can provide analgesic effects in the host. It is important to note that analgesia is a method to reduce pain and inflammation in a systemic fashion, as opposed to local anesthesia, which causes loss of sensation within a localized area; therefore, the primary role of a NSAID is to mitigate the pain associated with inflammation.

Serum cortisol results from this study showed a rapid increase immediately following castration, particularly in the castrated treatments (CAS and MEL). Although the CON group experienced a lesser increase in serum cortisol following sham castration, this suggests a stress response associated with handling alone. A review by Dantzer and Mormède (1983) summarizes that environmental stimulation causes hormonal changes, such as increased glucocorticoid concentration. There was an overall decrease in serum cortisol at h 1; however, the CAS group had a secondary cortisol increase evident at h 2.5. It is plausible that the initial increase in cortisol resulted from the combined effects of handling and castration stress experienced during castration whereas the secondary cortisol increase observed for CAS but not MEL is a delayed stress response to prolonged pain experienced without analgesia. Because meloxicam was administered concurrent with castration, its effects would not be realized until blood concentrations reached the therapeutic threshold. Although the pharmacokinetics of meloxicam were not directly measured in the current study, at h 2, the sharp decrease in cortisol concentration of the MEL group but not for the CAS group may corroborate the time required for orally administered meloxicam to reach efficacious blood concentrations in the animals. Prostaglandin E2 concentrations were reported to decrease at h 6 after dehorning in cattle administered oral meloxicam before the procedure (Allen et al., 2013). Additionally, oral meloxicam has been reported to reach mean peak plasma concentration within 11.64 h, with a mean residence time of 44.90 h, and has an elimination half-life of 27.54 h (Coetzee et al., 2009). At approximately 2 h following castration, Earley and Crowe (2002) reported a decrease in cortisol for castrates administered ketoprofen, a NSAID similar to meloxicam. A study that used transportation as a stress model reported that blood meloxicam concentration had an inverse relationship with circulating cortisol concentrations (Van Engen et al., 2014). In the current study, the suppression of cortisol was provisional, with concentrations being similar between castrated groups after h 3.5. Despite the seemingly short-term effects, meloxicam was efficacious in modulating the acute cortisol response in surgically castrated animals.

The acute phase response (APR) is a nonspecific component of innate immunity, which may respond to infection, inflammation, tissue damage, or stress (Baumann and Gauldie, 1994; Hughes et al., 2014). Biological responses associated with the APR include fever, production of APP by hepatocytes, and increases in circulating WBC (Carroll and Forsberg, 2007). The synthesis of APP is modulated by proinflammatory cytokines (i.e., TNF-α and IL-6) and perhaps cortisol (Carroll and Forsberg, 2007; Fisher et al., 1997). Haptoglobin is an APP that possesses anti-inflammatory actions by binding free hemoglobin, a proinflammatory protein, within the plasma (Murata et al., 2004). Haptoglobin can be used as a clinical parameter to determine the occurrence and severity of the inflammatory response in cattle (Makimura and Suzuki, 1982). The change in Hp concentrations from this study demonstrates that Hp was reduced in castrates that received oral meloxicam. This would indicate that meloxicam was able to reduce the magnitude of inflammation following castration, possibly due to the reduction in cortisol production. Likewise, Brown et al. (2015) reported a reduction in Hp for calves castrated and administered oral meloxicam at weaning, but no difference in Hp was observed when the same procedure was evaluated in neonates. Earley and Crowe (2002) also reported a decrease in serum Hp concentrations following castration with the administration of ketoprofen. Oral meloxicam administration also reduced Hp concentrations after transportation (Filho et al., 2014); however, Hp was not affected when various analgesic compounds were administered alongside a local anesthesia before dehorning of Holstein steers (Glynn et al., 2013). The febrile response is also a product of the APR. The current study showed an increased RT in the MEL group from h 40 to 48 compared with the CAS and CON groups, suggesting that meloxicam may result in a delayed febrile response in castrates. The delayed increase in RT could be a result of decreased serum meloxicam concentration at this time, and the timing of such is supported by pharmacokinetic investigation of oral meloxicam having mean residence time of 44.90 h (Coetzee et al., 2009). Ting et al. (2003b) reported a similar increase in RT of surgically castrated cattle administered ketoprofen compared with surgical castrates receiving no analgesia. Nevertheless, both MEL and CAS had a transient febrile response immediately following castration.

Total WBC, lymphocytes, and monocytes were elevated for both castrated groups when compared with the CON group, which is similar to results reported by Chase et al. (1995). However, oral meloxicam reduced concentrations of total WBC, neutrophils, eosinophils, monocytes, and red blood cells compared with CAS and hematological variables were also reduced by meloxicam administration before long-distance transport (Van Engen et al., 2014). When ketoprofen was administered before castration, no differences were observed in circulating leukocyte concentrations (Earley and Crowe, 2002). Ting et al. (2004) reported that hydrocortisone infusion to mimic castration had no significant effects on leukocyte concentrations. The reduction in some hematological parameters observed in this study for the MEL treatment may suggest that oral meloxicam reduces the magnitude of inflammation following castration because these concentrations were more similar to the CON treatment. Nevertheless, inflammation is an important process for tissue repair and resolution of infection, and field studies are needed to determine if meloxicam administration may impede healing from castration. However, Mintline et al. (2014) reported that administration of the NSAID flunixin meglumine had no effect on the rate of wound healing following surgical castration. Some NSAID, particularly cyclooxygenase-1 (COX-1) isoform inhibitors, are known to negatively affect thromboxane production and reduce platelet aggregation and thus have potential to impede hemostasis during surgical procedures (Aiello, 1998, p. 1820). However, COX-2–specific inhibitors such as meloxicam may be less likely to adversely affect platelets or coagulation because they preferentially inhibit the production of inflammatory-type PG such as PGE2 (Papich and Messenger, 2015). Regarding circulating platelet concentrations, Ting et al. (2003a) observed an increase in platelets for castrates administered ketoprofen compared with an untreated control. Conversely, we observed a decrease in platelets for castrated treatments; however, we did not observe a difference in platelets for MEL vs. CAS. We did not observe excessive blood loss in MEL, yet this was not of primary inference in our study and would require a larger number of animals to more clearly elucidate. Further research is needed to determine if meloxicam administration during surgical castration of beef cattle poses an increased risk for excessive blood loss.

The production of glucose from noncarbohydrate carbon substrates such as pyruvate, lactate, glycerol, and AA, known as gluconeogenesis, can be stimulated by cortisol (Carroll and Forsberg, 2007) resulting in an increase in blood glucose concentration. The current study observed an increase in blood glucose concentrations in the castrated animals compared with CON. In contrast to our results, Ting et al. (2004) reported no difference observed in glucose concentration following Burdizzo castration.

Although health and performance outcomes were not within the scope of the current study, recent field studies report decreased incidence of bovine respiratory disease morbidity (Coetzee et al., 2012) and increased performance (Brown et al., 2015) when oral meloxicam is administered around castration of beef cattle. The current intensive investigation of the stress and inflammatory responses corroborate these production-based findings and further support efficacy associated with the use of meloxicam to reduce inflammation resulting from surgical castration in beef cattle, which ultimately should improve clinical health and performance in the commercial production setting.

In conclusion, oral administration of meloxicam was able to diminish the cortisol response, which suggests that the physiological stress associated with surgical castration was reduced with oral administration of meloxicam at 1 mg/kg BW. Meloxicam also reduced the magnitude of the inflammatory response in castrates, as evidenced by a decrease in Hp and certain peripheral blood leukocyte concentrations. However, there was a delayed febrile response observed with meloxicam administration following castration. Development of pain management strategies could be useful to address both health and animal welfare concerns in the beef industry but further research is needed to determine whether administration of meloxicam or other NSAID may impede convalescence or hemostasis following surgical castration.

 

References

Footnotes


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