Editor’s note: Part II of a bovine pain series.

The need to study pain is multifactorial. Societal concerns for the humane care of food-production animals and the need to maintain consumer confidence that meat is being produced in a manner not injurious to the animals are of high importance. “Regulatory agencies’ concerns are that methods and procedures done on-the-farm and often without the input of a veterinarian are done with regard to the welfare of the animals,” says David Anderson, DVM, MS, Dipl. ACVS, Kansas State University.

“Livestock producers’ needs are to maintain a safe, wholesome product in a viable and sustainable marketplace without adversely affecting the business plan for the operation.”

Animal welfare activist groups are putting pressure on the livestock industry to change practices. “The livestock industry needs to actively monitor these groups’ activities, passionately participate in debate regarding regulation to ensure that only those that are truly beneficial are enacted, and promote the accurate image of farmers and ranchers as dedicated tenants of the land and guardians of the well-being of the animals under their stewardship,” says Anderson.

Animal rights groups have recently claimed a significant victory in the New Jersey supreme court, adds Hans Coetzee, BVSc, Cert CHP, PhD, Dipl. ACVCP, Kansas State University. “This decision has widespread implications for our profession, most notably, that castration in New Jersey cannot be considered humane without specific requirements to prevent pain and suffering,” Coetzee says. The Court reportedly made clear that the decision to permit these practices as long as they are done by a “knowledgeable person” and in a way to “minimize pain” could not “pass muster.”

 While legislation in New Jersey does not affect most of the major livestock-producing states, it does indicate that “routine husbandry practices” are on the list of targets for animal rights groups. “It also suggests that our position as custodians of animal health and well-being is being eroded by those with an animal rights agenda,” Coetzee notes. “The veterinary profession has a considerable amount of credibility among consumers. We should therefore be at the forefront of this discussion by proactively and scientifically addressing potential welfare concerns rather than become a victim of agenda-driven or well-meaning but ill-conceived legislation.”

Assessment of production parameters is critical if animal well-being research is to have relevance to livestock producers, Coetzee says. “These assessments may take the form of a cost-benefit analysis or a measure of animal performance. It is also recognized that processing calves on arrival with protocols that involve dehorning and castration negatively influences the health and performance of stocker cattle. Most of these effects have only been studied over a relatively short duration.”

Castration — pain and performance

The National Animal Health Monitoring System Beef 2007–2008 study indicates that almost 41% of cow-calf operations do not castrate calves prior to selling them. For operations that castrated bull calves, the percentage of operations using surgical castration was 49%, clamp/Burdizzo 3.5%, rubber band or tubing at less than 3 months of age 39.5%, and rubber band or tubing at more than 3 months of age 7.8%.

All methods of castration of cattle are considered to reduce performance on beef cattle. “Some authors believe that this can be attributed to removing the source of testosterone while others consider that this is associated with pain and inflammation associated with castration,” Coetzee explains “This effect may also be mitigated by the use of implants. It is generally accepted that castration in younger calves has less of a negative performance effect than older calves.” This could be attributed to the fact that the testicles in older calves are better developed, heavier and more vascularized which may be associated with more pain and inflammation following castration.

Previous research by Thomson et al determined that surgical castration in heavyweight cattle had less of an effect on long-term performance in calves than banding. Furthermore, they did not see any performance benefit associated with lidocaine administration in the spermatic cord and scrotum prior to surgical castration.

Production parameters are often too imprecise to reflect the pain experienced by animals following castration. “Using weight gain as an indicator of distress following castration may be confounded by a decrease in testosterone following removal of the testes,” Coetzee explains.

Many people intuitively believe that surgical castration causes sharp pain of short duration (minutes to hours) as compared to banding or Burdizzo which are thought to be associated with acute, followed by dull pain of long duration (hours to days), explains Anderson. “Much of this concern is based in anthropomorphizing rather than science. Research has been contradictory with some showing non-surgical castration and some showing surgical castration as having less profound impact on the calves. Our research is aimed at developing objective assessment algorithms that will remove the inherent biases that may explain some of the contradictory findings in the past.”

What’s normal?

Before Kansas State University researchers could assess the effects of castration, they had to first find out what was “normal” activity for the study calves. “Establishing ‘normal’ is a critical centerpiece for our research,” says Anderson. Much of the literature is difficult to compare directly because of varying environmental, management and breed variation. In the past, research interventions have caused variability that is difficult to filter out in the final analysis. “One of our goals is to implement new technology that allows us to remove these extraneous variables or to validate bio-markers that are robust and not susceptible to variations associated with these variables.”

Brad White, DVM, MS, Kansas State University, says they have found by using accelerometers to determine behavior, that a “normal” pattern may vary quite a bit between calves. “Our previous research has shown that some apparently healthy calves may spend 30% of their time lying while others spend up to 75% of their time lying,” White says. “This individual variation led us to conduct this research in a manner that allowed us to determine potential changes in behavior patterns by documenting behavior for that calf prior to the procedure, then evaluating potential changes after castration. Using these methods allowed us to find differences related to castration rather than focus on individual variability between calves.”

It is difficult to find a good definition of what “normal” behavior is because cattle show considerable inter-individual variation, Coetzee notes. He says during the “control” period the animal’s behavior is determined prior to castration. “During this time animals are subjected to all the procedures we will be performing during the study but no pain is inflicted,” he explains. “This may still not be ‘normal’ because animals are being housed separately, however, it does provide us with a frame of reference to compare each animal with itself.”

This type of research is a lot more powerful because each animal is its own control. “This will allow us to make specific inferences regarding animal behavioral changes relative to castration and dehorning,” Coetzee says. “The down side to this is that these studies are a lot more expensive and we are indebted to the USDA for funding this research.”

Activity post-castration

One of the clinical tools that has been used to assess post-surgical pain in cattle has been looking for decreased activity and increased lying time. “We are finding out that this is not true in many cases and probably has lead to some erroneous assumptions in the past,” Anderson says.

The K-State researchers were therefore surprised to find that the opposite appears to be the case for castrated calves. “One reason may be that castration produces an open incision that may be sensitive to the abrasive effects of bedding when the calves lie down,” surmises Coetzee. “It may also be that calves are trying to ‘walk off’ the dull inflammatory pain associated with castration.”

White says they expected some depression and lethargy following the procedure and were surprised at the standing and walking activity. “In this study we only followed the calves for 24 hours post castration; therefore, the behavior may have changed long-term. Also of interest was the fact that the disparity between pre- and post- castration time spent standing was most notable during the middle of the night when cattle typically spend much of their time lying.”

Pain can have other effects as well. Coetzee says it is well established that castration produces a cortisol response that peaks within 30 to 90 minutes of castration. Cortisol has immune suppressive effects although the relationship between this peak and long-term immune suppression is not well described. “Irish researchers have demonstrated that Bur-dizzo castration increased plasma cortisol and acute-phase proteins, and suppressed immune function and growth rates,” explains Coetzee. “This group also found that surgical castration decreased IFN-gamma production, ADG and increased haptoglobin and fibrinogen independent of plasma cortisol concentrations.”

Analgesia at castration

It has been suggested that a surgical stimulus such as castration in calves is so brief that little difference can be observed or measured between animals having or not having local anesthetic applied. However, some studies have shown that alleviating pain associated with surgical castration increases weight gain in cattle for 35 days following castration.

“We have demonstrated a similar effect,” Coetzee says. “This suggests that alleviating acute pain at the time of castration may have economic bene-fit.” Ketoprofen, a non-steroidal anti-inflammatory analgesic not approved for use in cattle in the U.S., has been shown to reduce acute plasma cortisol response in cattle following administration at the time of castration. “We have demonstrated a similar effect with IV sodium salicylate,” he adds. “Giving both a local anesthetic and intravenous ketoprofen before surgical castration was found to virtually abolish the post-surgery cortisol response. Ketoprofen given alone was also found to reduce the plasma cortisol response to Burdizzo castration more effectively than a local anesthetic or an epidural.”

Too often people focus on the immediate pain of the procedure without regard to the pain that may occur after that analgesic has worn off. “Existing literature would suggest that elimination of the acute, sharp pain associated with the procedure is the least offensive to the animal,” adds Anderson. “In our research, we hope to be able to determine what the variable benefits, or lack there of, of sustained analgesia are.”

What’s our perfect drug?

If Coetzee could choose, the perfect analgesic drug for cattle would have a convenient route of administration, a very rapid onset of activity, an extended duration of effect, a short withhold period, a wide margin of safety with a low toxicity or abuse potential, and would also be cost-effective to use.

“Unfortunately, many of these requirements are mutually exclusive,” Coetzee says. “For example if we do not give a drug intravenously, there will most likely be a delay in onset of activity due to absorption from the site of administration. Also, if a drug has a long duration of activity, it usually has a longer withdrawal time and persistent plasma concentrations may be associated with increased toxicity. We need to identify which are the critical components of an analgesic drug regimen that will provide maximum benefit for the animal and will also be convenient and cost-effective for the producer to use.”

This may, in fact, be a combination of drugs and not a single agent. “This is the concept of multimodal analgesia where we ‘attack’ pain perception at several points along the pathway from tissue damage through transduction, transmission and perception,” Coetzee explains. “Our research goal is to identify these therapies and design effective analgesic remedies that are cost-effective and convenient for producers to use routinely.”   

“One of the most exciting things about research is the ability to look at parameters once held as dogma and finding out that we may have been misinterpreting the signals,” Anderson adds.  

Where are the drugs?

The American Veterinary Medical Association “supports the use of procedures that reduce or eliminate the pain of dehorning and castrating of cattle”  and proposes that “available methods of minimizing pain and stress include application of local anesthesia and the administration of analgesics.” But a recent survey of 184 bovine veterinarians conducted by Kansas State University found that only 1 in 5 U.S veterinarians use anesthesia or analgesics at the time of castration.

“Administration of local anesthesia prior to castration and dehorning is legislated in several European countries, but there are currently no analgesic drugs specifically approved for pain relief in livestock by the U.S Food and Drug Administration,” says Hans Coetzee, BVSc, Cert CHP, PhD, Dipl. ACVCP.  FDA Guidance Document 123 for the development of effectiveness data for non-steroidal anti-inflammatory drugs (NSAIDs) states that “validated methods of pain assessment must be used in order for a drug to be indicated for pain relief in the target species.” “It is this requirement that our group hopes to address with our research,” Coetzee adds.

Currently, flunixin meglumine is the only NSAID formally approved for use in cattle in the United States, and is indicated for the control of pyrexia associated with bovine respiratory disease, endotoxemia and acute bovine mastitis. It is not formally approved for pain relief, although this class is recognized as having analgesic properties.

Salicylic acid derivatives including sodium salicylate and acetylsalicylic acid (aspirin) are still widely used as analgesic, antipyretic and anti-inflammatory agents.  Veterinary forms of aspirin are marketed with label indications for pain relief, fever and inflammation, but the drug has never been formally approved by the FDA Center for Veterinary Medicine for these purposes. A dose of 50–100 mg aspirin/kg bodyweight is commonly used for analgesia in cattle although the efficacy of this dose has not been conclusively demonstrated in peer-reviewed studies. Coetzee’s studies have found that maintaining plasma salicylate concentration above 30 micrograms/mL significantly attenuates plasma cortisol response following castration. “However, we have shown that oral aspirin formalizations typically have a very low bioavailability in ruminants and it is difficult to attain this concentration at the currently recommended doses.”

Salicylate also has a very short half-life in cattle, typically 30 to 45 minutes. This means that the drug has to be dosed more frequently to provide effective analgesia. “We currently do not recommend that veterinarians use oral aspirin to provide analgesia to cattle because of these factors,” Coetzee states.

In a recent study, 22 beef cattle were assigned to groups of uncastrated, untreated controls; castrated, placebo treated controls; castrated, IV xylazine (0.05 mg/ kg) and ketamine (0.1 mg/kg); and castrated, IV xylaxine (0.05 mg/ kg). Calves were castrated with a Henderson castration tool and blood samples were collected. Plasma ketamine, norketamine and xylaxine concentrations were associated with mitigation of plasma cortisol response. However, when the drug concentration decreased below the limit of detection, cortisol concentrations rebounded in the drug treated groups. “This suggests that although this drug combination was a very effective sedative-analgesic, it did not provide long-term analgesia,” Coetzee says.

Castration and performance studies

Work done by Kansas State University researchers found that castrating cattle decreases performance of feeder calves in the immediate post-castration period (35 days) in a study where implants were not administered. Calves surgically castrated had improved average daily gain (ADG) and gain efficiency (GE) relative to calves castrated by banding. Local anesthesia with lidocaine had no effect on performance, post-castration behavior or vocalization during castration.

Cattle with larger scrotums had higher vocalization scores during castration than cattle with smaller scrotal circumference. Castrating cattle at younger ages could result in less stress associated with event. “This research indicates that cattle needing castration on arrival at a stocker or feeding operation should be discounted for lost production associated with healing of castration sites,” notes Hans Coetzee, BVSc, Cert CHP, PhD, Dipl. ACVCP. “In these data, calves that were surgically castrated demonstrated  improved performance relative to calves castrated with a banding method. These data do not support a production benefit associated with the use of local anesthesia with lidocaine prior to castration of bull calves.”

Coetzee notes in other studies Burdizzo or surgical castration had no effect on ADG over a three-month period following castration. The ADG of 7-week-old calves during the five weeks following castration using rubber rings, clamp or surgery have been reported to be lower than non-castrated calves but similar between the different castration methods. Rubber ring and surgical castration were reported to cause a decrease in ADG of 50% and 70% respectively in cattle aged 8 to 9 months. “When 8, 9 and 14-month old cattle were castrated surgically or using latex bands, cattle castrated later had poorer growth rates than those castrated at weaning,” he explains. “Cattle castrated with latex bands also had lower growth rates than those castrated surgically during the following four to eight weeks.”

In an Oklahoma State University study, 162 bull calves were used to determine the effects of latex banding of the scrotum or surgical castration on growth rate. Bulls that were banded at weaning gained less weight than bulls that were banded or surgically castrated at 2 to 3 months of age. In a second study, 368 bull calves were used in two separate experiments to examine the effect of method of castration on receiving health and performance.

“In the first experiment, latex banding intact males shortly after arrival was found to decrease daily gain by 19% compared with purchasing steers, and by 14.9% compared with surgically castrating intact males shortly after arrival,” Coetzee says. “In the second experiment, purchased, castrated males gained 0.58 lbs more and consumed 1.26 lbs more feed per day than intact males surgically castrated shortly after arrival.