Written by L. CHRIS SANCHEZ | DVM, Ph.D., DACVIM

Colic and lameness are two of the most clinically and economically important medical problems facing horses and their owners. Pain is a critical component of each disease process, and its alleviation is critical to a successful outcome. A limited number of analgesics are available for use in horses, and many are associated with significant untoward effects. This article will focus on methods used for the recognition of pain in horses and available options for analgesic drug use.

Equine Pain Scoring Systems

Useful pain scoring systems should include the following traits: clearly defined assessment criteria, usable by all observers, simple and quick to use, sensitive, identified strengths and weaknesses, and validated. Possible deficiencies include bias, inter- and intraobserver variability. A lack of agreement between observers is one of the flaws of simple scoring systems, such as the visual analogue scale (VAS) in which pain is scored on a numerical scale when used in humans. Continuous video assessment allows for quantification of either time budgets (locations within the stall, ear position, head position, eating, lying down, etc.) or events (vocalizing, stomping feet, shifting weight, etc.). This relatively objective form of analysis has been performed on horses following arthroscopy (Price, Catriona et al. 2003). A numerical rating system was used to show the beneficial effect of a butorphanol constant rate infusion for analgesia following colic surgery (Sellon, Roberts et al. 2004). Facial pain scoring systems have recently been proposed for use in horses (Dalla Costa, Minero et al. 2014; Gleerup, Forkman et al. 2015). Similar scoring systems have been used in humans and rodents, and clearly show promise for use in horses as well. Objective measures, such as vital signs, plasma cortisol concentration and force plate analyses, alleviate the subjective nature of assessment, but vital signs and cortisol are affected by a variety of factors in addition to pain, including hydration status, perfusion, sepsis and/or endotoxemia, fear, and anxiety. Because of this, they are not specifically useful indicators of pain.

Analgesic Agents

Nonsteroidal anti-inflammatory drugs (NSAIDs)

A complete discussion of NSAID use in the horse is beyond the scope of these proceedings. Flunixin and phenylbutazone are used most commonly. Firocoxib has demonstrated COX-1 sparing effects in the horse; an initial loading dose is important for analgesia. Acetaminophen provides an alternative option and was recently shown to have similar efficacy to flunixin in a foot pain model when used alone and similar efficacy to phenylbutazone when combined with firocoxib (Foreman, Foreman et al. 2015)

Morphine has been used with varying success in horses. Some practitioners and researchers have reported fantastic results, while others have concerns. It’s a great analgesic but has a short duration of action and, as with all opioids, delays gastrointestinal transit. Buprenorphine appears to have a good safety and efficacy profile in horses, with the advantage of a longer (eight to 12-hour) duration of action (Love, Pelligand et al. 2015). Buprenorphine is a fantastic option as it has all the positive attributes needed for a good opioid — the major downside is cost in the US.

Opioids
All opioids have the potential for adverse effects in horses, including increased locomotion and excitement and decreased gastrointestinal motility. Butorphanol has been the most widely used opioid in horses. Intravenous use can be associated with excitement, ataxia, and increased locomotion when used alone. For short procedures, it is best combined with an α-2 agonist. Intramuscular administration results in decreased systemic availability (37 percent). When used as a constant rate infusion (CRI), behavioral and gastrointestinal adverse effects are reduced (relative to single injection) in normal horses. One report demonstrated decreased weight loss, improved recovery characteristics, and earlier discharge from the hospital when administered for 24 hours after colic surgery (Sellon, Roberts et al. 2004).

Transdermal fentanyl patches would, theoretically, provide a fantastic route of opioid administration in horses. Unfortunately, uptake from the patches is highly variable, and extremely high plasma concentrations (associated with agitation in some horses) are needed for MAC reduction (Thomasy, Steffey et al. 2006), or visceral or somatic anti-nociception in healthy horses (Sanchez, Robertson et al. 2007).

Tramadol is an analog of codeine, but it has less abuse potential and fewer cardiorespiratory side effects than drugs classified as opioids. Tramadol has a short half-life and very low oral bioavailability (~3 percent) in horses and does not appear to provide effective analgesia when used alone. In a clinical setting, tramadol alone failed to provide pain relief in horses with naturally occurring laminitis but did appear to help when used in combination with ketamine (Guedes, Matthews et al. 2012).

Alpha2-adrenoceptor agonists

Alpha2-adrenergic agonists are frequently used for both sedation and short-term analgesia. These drugs are not ideal for prolonged analgesic therapy as they cause an immediate and profound decrease in gastrointestinal motility, amongst other cardiovascular effects, and have a relatively short duration of action. Importantly, one should note that sedative effects may require lower dosages and/or last longer than analgesic effects with most drugs in this class. Alpha2-adrenergic agonists provide dose-dependent visceral and somatic anti-nociception of varying duration, as well as an opioid-sparing effect. Thus, a combination of an alpha2-adrenergic agonist and opioid provide a variety of commonly used multimodal analgesic protocols.

Sodium channel blockers

Lidocaine is an aminoamide local anesthetic which prevents propagation of action potentials by binding to voltage-gated sodium channels. Lidocaine, administered as an intravenous infusion, is commonly used in horses for its potential analgesic, prokinetic and anti-inflammatory properties. Clinical signs of toxicity in conscious horses include skeletal muscle tremors, altered visual function, anxiety, ataxia, and collapse. Moderate evidence in clinical and research settings support its use as a visceral and somatic analgesic agent. Drug accumulation can be noted in a clinical setting after prolonged administration, and lower infusion rates should be used in horses receiving highly protein-bound drugs.

N-methyl-D-aspartate antagonists

Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist and can modulate central sensitization and exert an anti-hyperalgesic effect at sub-anesthetic doses. Anti-nociception has not been demonstrated in healthy horses receiving infusions of ketamine (Fielding, Brumbaugh et al. 2006), but, in clinical settings, there seem to be some beneficial effects (Wagner, Mama et al. 2011; Guedes, Matthews et al. 2012). In laminitic horses, the addition of ketamine resulted in decreased blood pressure, decreased forelimb offloading frequency, and increased forelimb load, relative to tramadol alone (Guedes, Matthews et al. 2012).

Antispasmodic medications

N-butylscopolammonium bromide (NBB) has both anticholinergic and antispasmodic properties and is labeled for the treatment of spasmodic colic. NBB administration also decreases rectal tone, facilitating rectal examination and may be useful in horses with esophageal obstruction.

Multimodal therapy

In severely painful horses, the combination of ketamine with lidocaine and/or butorphanol could potentially provide additional analgesia, relative to the infusion of a single drug. In healthy horses, butorphanol-containing combinations resulted in delayed total gastrointestinal time and reduced fecal output (Elfenbein, Robertson et al. 2014); thus, one should pay careful attention to fecal output when using said combinations.

Dr. Christine Sanchez received her DVM degree from the University of Florida in 1995. She then completed an internship at Equine Medical Associates in Edmond, Oklahoma. After finishing a residency in large animal internal medicine at the University of Florida, she became a Diplomate of the American College of Veterinary Internal Medicine in 1999. She completed her Ph.D. at the University of Florida in 2003 and is currently a professor of large animal internal medicine. She is also currently the director of the Hofmann Equine Neonatal ICU and the chief medical officer of the UF Large Animal Hospital. Dr. Sanchez’s clinical interests include general equine internal medicine, neonatology, and gastroenterology. Her research focus has been veterinary gastroenterology with a special interest in visceral pain and gastric ulceration.

References

• Dalla Costa, E., M. Minero, D. Lebelt, D. Stucke, E. Canali, & M. C. Leach. (2014). “Development of the Horse Grimace Scale (HGS) as a pain assessment tool in horses undergoing routine castration.” PLoS One, 9(3), e92281.
• Elfenbein, J. R., S. A. Robertson, R. J. MacKay, B. KuKanich, & L. Sanchez. (2014). “Systemic and anti-nociceptive effects of prolonged lidocaine, ketamine, and butorphanol infusions alone and in combination in healthy horses.” BMC Vet Res, 10 Suppl 1, S6.
• Fielding, C. L., G. W. Brumbaugh, N. S. Matthews, K. E. Peck, & A. J. Roussel. (2006). “Pharmacokinetics and clinical effects of a subanesthetic continuous rate infusion of ketamine in awake horses.” Am J Vet Res, 67(9), 1484-1490.
• Foreman, J. H., C. R. Foreman, & B. E. Bergstrom. (2015). “Medical alternatives to conventional cyclooxygenase inhibitors for treatment of acute foot pain in a reversible lameness model in horses.” Journal of Veterinary Internal Medicine.
• Gleerup, K. B., B. Forkman, C. Lindegaard, & P. H. Andersen. (2015). “An equine pain face.” Vet Anaesth Analg, 42(1), 103-114.
• Guedes, A. G., N. S. Matthews, & D. M. Hood. (2012). “Effect of ketamine hydrochloride on the analgesic effects of tramadol hydrochloride in horses with signs of chronic laminitis-associated pain.” Am J Vet Res, 73(5), 610-619.
• Love, E. J., L. Pelligand, P. M. Taylor, J. C. Murrell, & J. W. Sear. (2015). “Pharmacokinetic-pharmacodynamic modelling of intravenous buprenorphine in conscious horses.” Vet Anaesth Analg, 42(1), 17-29.
• Price, J., S. Catriona, E. M. Welsh, & N. K. Waran. (2003). “Preliminary evaluation of a behaviour-based system for assessment of post-operative pain in horses following arthroscopic surgery.” Veterinary Anaesthesia and Analgesia, 30(3), 124-137.
• Sanchez, L. C., S. A. Robertson, L. K. Maxwell, K. Zientek, & C. Cole. (2007). “Effect of fentanyl on visceral and somatic nociception in conscious horses.” J Vet Intern.Med, 21(5), 1067-1075.
• Sellon, D. C., M. C. Roberts, A. T. Blikslager, C. Ulibarri, & M. G. Papich. (2004). “Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy.” J Vet Intern.Med., 18(4), 555-563.
• Thomasy, S. M., E. P. Steffey, K. R. Mama, A. Solano, & S. D. Stanley. (2006). “The effects of i.v. fentanyl administration on the minimum alveolar concentration of isoflurane in horses.” Br.J Anaesth., 97(2), 232-237.
• Wagner, A. E., K. R. Mama, E. K. Contino, D. J. Ferris, & C. E. Kawcak. (2011). “Evaluation of sedation and analgesia in standing horses after administration of xylazine, butorphanol, and subanesthetic doses of ketamine.” J Am Vet Med Assoc, 238(12), 1629-1633.

This post was written by FVMA Communications.