New Perspectives on the Pain Drain

Most veterinarians stock the drawers in their mobile units so that the easiest containers to reach when they open the drug compartments are the pain medications. Whether the situation is an emergency call to tend a horse that has acute abdominal pain, or an elective call for a horse that is an enthusiastic athlete with an ongoing lameness problem, providing better pain management in horses is a growing concern among owners and practitioners.

According to Anthony Blikslager, DVM, PhD, associate professor of equine surgery at North Carolina State University's College of Veterinary Medicine, improvements in pain management in horses can be achieved by developing new drugs, but just as important are improving our ability to recognize more subtle signs of pain and better using drugs that are already available.

Pain Detection
Blikslager says that untreated pain has adverse effects that impede healing and tissue regeneration. Therefore, the requisite first step in improving pain management in horses is increasing our awareness of pain. Although some individuals are more tolerant of pain than others, as a species horses are stoic and can hide many conditions that cause mild or moderate pain. The horse standing quietly in his stall might not be pawing or pacing, but subtle clues in his posture and behavior might yield evidence that all is not well.

Debra Sellon, DVM, PhD, associate professor of equine medicine at Washington State University in Pullman, has described a scoring system to assess the severity of a horse's pain. She assigns a horse a score based on posture, where the horse prefers to stand in the stall, and the degree of interaction with humans or other elements of his environment.

A healthy horse will typically stand at or near the stall door, facing out, with his head above the level of the withers. A horse in pain is more likely to stand in the middle or back of the stall, with the head in a lowered position, and not flicking its ears in response to noise or otherwise indicating interest in the surroundings.

Veterinarians might one day be able to look at molecules circulating in the blood that are released in response to pain. Blikslager said he and his colleagues are investigating the usefulness of measuring blood levels of pain mediators such as catecholamines (hormones related to adrenaline) and endorphins, which increase in painful states. If an assay for pain mediators in a horse's blood can be developed, veterinarians could detect pain even in stoic, quiet horses.

Controlling Pain
After recognizing pain, the next step is developing better ways to control it. Better might mean increased effectiveness in some situations, and a higher margin of safety in others. Multimodal pain management is a common buzzword in veterinary medical circles. "Multimodal pain management refers to administering several different types of drugs via different routes of delivery," said Blikslager. "Combining drugs with different modes of activity is an improvement over increasing the doses of a single drug in an effort to enhance pain control, especially if that drug is of the non-steroidal anti-inflammatory class."

Giving different classes of drugs (intravenously, orally, and/or transdermally) at the same time enables the doses of each to be decreased. Horses benefit from such combinations because different drugs administered by different routes not only result in additive painkilling effects; they also minimize or eliminate the adverse effects of the same drugs given alone at higher doses.

Although non-steroidal anti-inflammatory drugs (NSAIDs) are found in the first aid kits of many horse owners, their use can be accompanied by risk of gastrointestinal ulceration and, to a lesser extent, kidney injury. According to Blikslager, giving a horse two NSAIDs, such as phenylbutazone and flunixin, concurrently increases the likelihood of important adverse effects. Horses that are dehydrated, not eating well, or that have other medical conditions are at higher risk of developing adverse effects from NSAIDs, but often those horses are the ones that need pain medications. Therefore, reducing the dose of these potentially harmful drugs by giving them in combination with drugs that act via alternative routes is an appealing strategy for veterinarians and owners caring for a painful horse, especially when needed over a period of time.

Blikslager said another way to minimize adverse effects is using a preparation that is delivered directly to the affected area (topically or locally), but does not end up in the horse's general blood circulation (systemic) in high concentrations. A good example is the topically administered non-steroidal anti-inflammatory cream containing diclofenac (Surpass), which circumvents delivery of the drug to the horse's other organs, including the gastrointestinal lining and kidneys. The product is intended for application to the skin of the carpus, hock, and lower limb joints. In some instances, use of the cream can permit oral dosing of phenylbutazone or flunixin to be substantially reduced or even discontinued.

Administering drugs that target precise inflammatory pathways instead of general pathways is another way of limiting adverse effects of analgesics. COX (cyclooxygenase) selective inhibitors are targeted medications. Cyclooxygenase is an enzyme that generates inflammatory mediators called prostaglandins. NSAIDs inhibit the cyclooxygenase pathway and hence the production of prostaglandins. The problem is that certain prostaglandins are necessary for maintaining adequate blood flow to the inner surface of the stomach and certain areas of the kidneys. When all prostaglandins are curtailed by drugs, gastrointestinal and kidney damage can result.

Researchers are trying to develop drugs that target pain-mediating prostaglandins while sparing the gut- and kidney- protective prostaglandins. Because the enzyme that results in production of the pain-mediating prostaglandin is called cylooxygenase 2, scientists are evaluating drugs called COX-2 inhibitors as pain treatments. At present, there are no COX-2 inhibitor drugs labeled for use in horses in the United States, but they are available for use in dogs. Continued research might result in their approval for equine administration. COX-2 inhibitors often have the word "cox" in the proprietary or generic name. Firocoxib (Previcox) is a COX-2 inhibitor available for use in dogs, and published conference abstracts suggest it is effective for treating equine hoof pain.

Blikslager said there is an alternative generation of COX inhibiting drugs, the COX-3 inhibitors, which include drugs such as dipyrone. This drug has a similar mode of action to acetaminophen (marketed for humans as Tylenol) in its interruption of pain pathways in the central nervous system.

Investigators revisiting the actions of these drugs and those of phenylbutazone and flunixin are finding many have pain-controlling activity at lower doses. This is important because after colic surgery the single most important factor determining a horse's survival is the length of time that elapsed between the first signs of colic and initiation of surgery. Often, the full doses of NSAIDs have been given by the owner or primary-care veterinarian, perhaps multiple times, by the time the horse arrives for surgery, despite the fact that the label specifies that doses should only be given every 12 hours. This not only masks the signs of pain that would have prompted the horse's transport to the surgical facility sooner, but is deleterious to the horse's physiology.

Blikslager stresses that the preferred scenario is the one in which the severity of the horse's condition is promptly recognized and the decision to refer the horse is made sooner in the course of the problem. This will increase the horse's prognosis for survival, and it is more likely if low doses of pain medication were given initially.

All drugs have potential adverse effects. The best way to get the optimal combination of safety and effectiveness out of pain medications is to give the lowest effective dose for the shortest time possible. Always work with your veterinarian when administering medications to your horse, because the best combination therapy of all is a care team that involves the educated owner and the veterinarian.

About the Author

Kim A. Sprayberry, DVM, Dipl. ACVIM

Dr. Kim A. Sprayberry, DVM, Dipl. ACVIM, is an internal medicine specialist at Hagyard Equine Medical Institute in Lexington, Ky. When not working with horses, she enjoys pursuits in medical journalism and editing as well as kayaking and American southwest archaeology.

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