Study shows tramadol has no effect on osteoarthritis pain scores

When researchers attempted to demonstrate measurable effects of tramadol on osteoarthritis pain, they came up empty. (Shutterstock.com)Researchers from the University of Georgia have found that tramadol is ineffective in alleviating signs of pain associated with osteoarthritis in dogs, according to a release from the Morris Animal Foundation (MAF), which funded the study. The research team published their results in the Feb. 15 issue of the Journal of the American Veterinary Medical Association.

“The data shows conclusively that tramadol is not an effective drug in treating the pain associated with arthritis in the dog, despite its common recommendation,” says Steven Budsberg, DVM, MS, DACVS, professor of surgery and director of clinical research at the University of Georgia College of Veterinary Medicine, in the MAF release. “This use of tramadol is a classic example of failing to acknowledge and control for bias when evaluating a potential treatment.”

The team at the University of Georgia, led by Dr. Budsberg, compared the use of tramadol with both a placebo and the nonsteroidal anti-inflammatory drug carprofen in client-owned dogs in a randomized, blinded, placebo- and positive-controlled crossover study, according to the study abstract.

Dogs with osteoarthritis of the elbow or knee were assigned to receive each of the three treatments in a random order, with each treatment arm lasting 10 days. Improvement was measured using vertical impulse, peak vertical force and Canine Brief Pain Inventory scores to assess gait and pain levels. The results showed no improvement when tramadol was given compared to either baseline or placebo. Carprofen was associated with significant improvement in results.

We reached out to several veterinary pain experts who contribute to dvm360 and the Fetch dvm360 conferences for their thoughts on the study. As experts often do, they diverge in their assessment of whether tramadol has a role in veterinary practice going forward.

Opinion No. 1: ‘Why would you use it?'

Dr. Michael PettyMichael Petty, DVM, CVPP, CVMA, CCRT, CAAPM, owner of Arbor Pointe Veterinary Hospital and Animal Pain Center in Canton, Michigan, comes down squarely on the “don't use it” end of the spectrum. He says veterinary pain experts have known for a number of years that orally administered tramadol doesn't work well for the treatment or prevention of acute pain, “and those of us with pain practices have suspected for several years that tramadol doesn't work for chronic pain either,” he continues.

“This is based on personal experience-not always the best measure-and on some pharmacokinetic studies showing that the active metabolite is not detectable in many dogs receiving tramadol, even those receiving several hundred milligrams per dose,” he says. “The study by Budsberg and his colleagues is a good one and underlines that tramadol is not a drug that can be depended on for chronic pain issues.” 

Dr. Petty says tramadol is a serotonin reuptake inhibitor, which can help with mood, and this could account for what some people see as a positive result when giving it. But it also has a history of causing serotonin syndrome, even at small doses and upon the first administration to a particular dog or cat.

“You have a drug that is a controlled substance, has the potential for human abuse, has no studies showing it works in either acute or chronic pain, and might kill your patient,” Dr. Petty concludes. “Everyone who wants to prescribe it to a patient needs to imagine the courtroom scenario where you're trying to defend your decision to use it on an animal that came to harm.”

Opinion No. 2: ‘My patients benefit'

Dr. Dani McVetyLike Dr. Petty, Dani McVety, DVM, founder and CEO of the Lap of Love Veterinary Hospice network, says the study results are not unexpected. “I looked at the study, but I didn't really have to,” she says. “It's truly no surprise to me or anyone else who's been using tramadol for years that it's not the perfect pain medicine.”

But she says hospice practitioners occasionally need to push the boundaries on medical comfort measures, and for her, tramadol will continue to have a role in managing veterinary pain.

“When I prescribe tramadol, I tell my clients that it's not used directly for pain reduction, but more like a glass of wine,” she says. “Sometimes you need one; sometimes you need two or three to get calmed down a bit. But if we're leaning on a very high dose for more than one to two nights, we have a quality of life issue and need to have a separate conversation.”

In other words, Dr. McVety uses tramadol in a limited capacity to get a very specific reaction from the pet: calmness. “Sometimes just reducing the emotional wind-up that occurs with pain is helpful to our clients and their pets,” she says. “This is why we will not stop using this medication, combined with adequate pain relief.”

Opinion No. 3: ‘The jury is still out'

Dr. Ralph HarveyRalph Harvey, DVM, MS, DACVAA, is associate professor of anesthesiology at the University of Tennessee College of Veterinary Medicine. He says trying to understand all the nuances of how living things experience pain-and how various drugs affect that experience-is like trying to answer the question “What is truth?”

“I have a great deal of faith in Budsberg and the validated models he uses,” Dr. Harvey says. “The work he has done is meaningful and useful, while not surprising. But many veterinarians far more well-known and expert than I am continue to advocate for the use of tramadol. And veterinarians continue to have the impression that it's beneficial.”

When Dr. Harvey gives talks on pain management, he asks participants to raise a hand if they've heard experts say there's little to no evidence supporting the use of tramadol in veterinary patients. Many hands go up. “Then I ask how many of them are using tramadol anyway,” Dr. Harvey says. “And many hands go up or stay up.”

In the pyramid model of evidence-based medicine, Dr. Harvey continues, double-blind placebo-controlled studies such as Dr. Budsberg's rank higher than the bottom level of expert opinion and clinical impression, which can be clouded by bias and wishful thinking. But still, he believes the jury is out on whether tramadol has value in mitigating the experience of pain in veterinary patients.

The problem, he proposes, lies in thinking of tramadol as an analgesic. “We do better to think of it as an emotion-modifying drug-at least in those animals that produce the right metabolite,” he says. “Dogs are extremely variable in their ability to produce that mu-receptor-binding metabolite. Some dogs do; others don't.”

Dr. Harvey refers to the work of psychologist Ronald Melzack, who several decades ago presented a theory differentiating between two aspects of pain. The discriminative aspect of pain, Melzack says, is highly localized, specific and sharp-it's what you would experience if you touched a hot stove. The affective aspect of pain is not how it feels but how it makes us feel-it's the suffering or emotional component of pain.

“The affect of pain is less distinct and slower to come across, and it degrades engagement with life,” Dr. Harvey says. “It's what Freud was talking about when he said a man with a toothache cannot be in love.”

Of course, no validated assay exists for the emotional experience of animal pain, so it's extremely difficult to provide evidence that a drug like tramadol is efficacious in relieving it. Another confounding factor is that tramadol is best used as a complementary therapy, Dr. Harvey says, which muddies the waters in terms of knowing which drug is causing which effect.

“But absence of evidence is not evidence of absence,” Dr. Harvey says. “Our greatest limitation in evaluating pain is our ability to recognize and quantify it, especially when it comes to validated models for the suffering aspect of pain. This is a new frontier we are only just beginning to explore.”

Issues surrounding tramadol use-its status as a controlled substance, the potential for human abuse and diversion, the risk of adverse effects such as serotonin syndrome, and patients' varied ability to metabolize the drug-must all play a role in an individual veterinarian's decision to use it or not. But is this study the last word on the subject? No, Dr. Harvey says.

“My impression is that, while I have great respect for this study, the metric is limited to the sensory rather than the emotional component of pain,” he says. “But Dr. Budsberg has elevated the conversation, and this is a rich area for continued discussion.”