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Patching up equine pain

Posted: Saturday, September 21, 2002

Innovative delivery systems for painkillers avoid adverse side effects associated with narcotics

Powerful narcotic painkillers such as morphine and fentanyl are mainstays in human medicine, but veterinarians are reluctant to use them to relieve acute pain in horses because of their serious side effects.

A dose strong enough to ease pain that cannot be managed by less powerful drugs often causes excitability, sweating, increased heart rate, high blood pressure, incoordination, and intestinal shutdown in horses.

Part of the problem is that the method of administration-intravenous or intramuscular injection-delivers a large dose at once to sustain pain relief over several hours. A researcher with the Equine Health Studies Program at Louisiana State University, Glenn Pettifer, D.V.M., has solved the problem by adapting the fentanyl skin patch used in human medicine for equine use. Fentanyl is a synthetic opioid, which is 30 times as strong as morphine and is used to control severe pain, typically in patients in final-stage cancer.

In the study "The Analgesic Efficacy and Side Effects of Transdermally Administered Fentanyl in Horses," financed by the Morris Animal Foundation, Pettifer applied commercially available transdermal patches impregnated with fentanyl to the front leg of each research horse. He then measured the level of pain relief and monitored the horse's movement to measure adverse side effects that cause excitability.

To determine pain relief, Pettifer used a skin-twitch test. A concentrated light was focused on the skin of the withers, and the time it took for the horse's skin to twitch in response to the light indicated the level of pain relief received from the transdermal patch.

Movements recorded

Each time the horse's movement broke a light beam, it was noted. Research horses experienced a high level of pain relief but remained placid.

Although all the data from this ongoing study have not been compiled, preliminary results indicate strong clinical success, Pettifer said. "There is an occasional horse that will become more restless or pace the stall, and you just discontinue the treatment or reduce the dose," he said.

Each 2x3-inch patch delivers 100 micrograms per hour of fentanyl; two or three patches used simultaneously are needed per horse to provide pain relief for up to 72 hours. Because the patch is already available for human use from most pharmacies, Pettifer said, veterinarians could begin to use it on horses as soon as they are satisfied with the results of his study.

"This provides a means of delivering a drug over a long period of time that doesn't involve having to use more invasive routes of administration like intravenous, intramuscular, or oral administration, which can be fairly stressful for the horse," Pettifer said. "You just clip a patch of hair off the front leg and apply the patch.

"A lot of analgesia issues in horses are dealt with using [nonsteroidal anti-inflammatory drugs], such as phenylbutazone and Banamine, or the next level, Torbugesic. For a horse that is unresponsive to these drugs, this might be something that we would move to, but we don't want veterinarians to use it right off the bat."

Use of the transdermal patch in horses opens up the door to other medications that could possibly be delivered in the same manner. "If we have analgesics that we can administer transdermally that provide us with more consistent blood levels, then we are going to get better pain management," Pettifer said.

"One of the reasons we like using the patch is that it avoids those peaks and valleys of the blood concentration of the drug that you get when you are doing intermittent injections," he said. "And, for example, when you have a situation where an owner has to administer a medication and for some reason can't or won't give injections, it certainly would be useful."

Pettifer said small-animal practices have employed transdermal patches to administer drugs other than analgesics, but not all drugs lend themselves to this method of administration.

Interrupting pain cycle

Pre-emptive analgesia-blocking pain before it occurs-is enjoying a lot of success in animals, as well as in humans, said Steven Kamerling, Ph.D., who heads the drug-discovery unit of Pharmacia Animal Health. Formerly a researcher at LSU who specialized in analgesics for horses, Kamerling said the procedure is especially useful for surgical cases.

During general anesthesia, pain signals are transmitted through the spinal cord even though receptors in the patient's brain do not react to them. Repeated pain signals from the site of an injury in effect fray the nerves in the spinal cord and make them more sensitive to pain when the animal emerges from anesthesia. "Introducing painkillers into the joint closes the gates of pain to the spinal cord," Kamerling said.

When used before arthroscopic surgery, for example, this experimental procedure seemed to reduce pain and soreness after surgery, Kamerling said. "This is an attempt to prevent the spinal cord from being hit with all these pain signals," he said

Pettifer added that, although opioids such as morphine work primarily on the central nervous system to dull pain messages to the brain, studies now show that certain membranes in the body also have opioid receptors. Synovial membranes in joints are rich with these receptors, and inflammation actually increases their number, making pre-emptive analgesia especially useful in joint surgery.

Another procedure, central hyperalgesia, attempts to desensitize the spinal cord before the cycle of pain sets in. "Early experiments have utilized low doses of intravenous ketamine or low doses of local anesthetics, such as lidocaine and xylocaine given intravenously, to try to shut down the chronic pain impulses," Kamerling said.

"Equine veterinarians are injecting very small doses of opiate molecules into joints, because the opiates also may act on pain receptors right in the joint," he said. "Some orthopedic surgeons on the human side of medicine are going in with morphine injections into a joint."

But Kamerling cautioned racetrack practitioners on its use. "If you do this to get a horse sound and get it into a race, most laboratories will pick it up in the post-race test," he said. "They can pick up very small amounts of opiates delivered into any body space, because it gets absorbed into the bloodstream and then into the urine of the horse. Just because [the joint] is an isolated compartment doesn't mean that it doesn't have a blood source."

Gentler joint injections

Iontophoresis, called the electric syringe, is a means of delivering drugs into joints and other areas without pain, trauma, or the danger of infection associated with injections. Using iontophoresis, a horse could enjoy its breakfast while having its hocks electrically injected, and it will feel only a slight tingling sensation.

Iontophoresis is accomplished by a principle similar to a magnet, in which the same poles repel. A drug whose chemical composition contains salt (or is salt-like in nature) bears an electrical charge that is predominantly either negative or positive. The drug is placed on a series of pads surrounding the affected area, which is then charged with an electrical current of the same polarity. The electrical current repels the drug and drives it through the skin and into the joint, tendon, or muscle. Unlike a needle injection, which delivers a drug to a limited area, the iontophoresis pads spread the drug evenly across and through the whole structure being treated.

Because no pain or risk of infection is associated with iontophoresis, drugs can be administered more frequently at a lower dosage, rather than once every six weeks at a dosage high enough to produce adverse side effects. This procedure has been used successfully to treat such ailments as inflamed joints, bowed tendons, and bucked shins.