Along with steroids and antibiotics, painkillers are one of the most common groups of drugs given to dogs by vets. One you may have heard of or even had prescribed for your dog is tramadol. But did you know that there is actually a debate in the veterinary world over whether tramadol is a good painkiller for dogs, and whether it even works for all dogs? Today we will investigate these debates.
What is Tramadol and Why is it Used?
Tramadol is a partial opioid painkiller primarily given as a tablet. There are also injectable and oral liquid forms available. Tramadol is licensed for use in dogs, meaning it can be legally prescribed as a first line drug by veterinarians. Tramadol is not licensed in cats or other species, so can only be given to them on the cascade. It is a schedule 3 controlled drug, meaning vets must ensure it is securely stored in a locked cupboard.
The licensed forms of tramadol are used for “the reduction of acute and chronic mild soft tissue and musculoskeletal pain”. Higher doses of tramadol can cause sedation and drowsiness in some animals. It can also cause nausea and vomiting, and rarely seizures in patients that are already prone to seizures. Care must also be taken in animals with liver diseases, as the drug may not be able to be broken down effectively.
How Does Tramadol Work?
As an opioid painkiller, tramadol works primarily on opioid receptors, mostly mu-receptors. Mu-receptors are found in the brain, spinal cord and nerves, as well as the intestines. Tramadol also has effects on other opioid receptors too, though, as well as non-opioid receptors in the body. The process for how opioid receptors work is very complicated. But in short, when a drug like tramadol activates mu-receptors, it blocks the transmission of signals along nerves. This means that the nerves cannot transmit a pain signal, so pain is not felt by the human or animal. This is analgesia. Tramadol also has more complicated pain killing effects by preventing the re-uptake of noradrenaline and serotonin, and releasing serotonin elsewhere.
Tramadol is a partial opioid-agonist, meaning that even when 100% of mu-receptors have been activated, the response cannot be 100%. This is in contrast to full opioid-agonists, like methadone or morphine; which will have 100% response when 100% of receptors are activated. This means tramadol will theoretically produce less analgesia when compared to these drugs, but will also have less side effects.
Before tramadol can have any analgesic effect in the body. However, the drug must be broken down by the liver to O-desmethyltramadol, which can then activate mu-receptors (as well as to other substances that activate other pain receptors). We know that dogs produce lower levels of O-desmethyltramadol compared to humans when administered tramadol.
Why Does Tramadol Not Work in All Dogs?
Many drugs in veterinary medicine have their origins in human medicine, and tramadol is no exception. First being used under the cascade and more recently in its licensed forms, it was assumed that it had the same analgesic effects in dogs and cats as it does in humans. And indeed, the opioid system in dogs is quite similar to that in humans. However, there have recently been claims that tramadol does not work in some dogs; leading to questions over whether it should be on vets’ shelves.
The major reason why tramadol may show a lack of efficacy in some dogs is their lack of specific enzymes in the liver that break down tramadol into its active form
Remember that tramadol must be converted to other substances before it can activate receptors. This is done by enzymes in the liver. It is known that these enzymes are altered or even missing in certain breeds of dog, altering the metabolism of tramadol. One study of 15 Beagles showed that they produced very low levels of O-desmethyltramadol; which was theorised to be caused by low metabolism of tramadol. Another study of 6 mixed breed dogs found even lower levels of O-desmethyltramadol, perhaps indicating those 6 dogs metabolised the drug even less than the Beagles.
One other reason is short elimination half-life
This is the time it takes for half the drug to be removed from the body – the faster this is, the quicker the drug is removed and thus the less time it is active in the body. The study of mixed breed dogs found that the elimination half-life was significantly lower than in humans. The study in Beagles found similar results. This is why tramadol is usually given more frequently in dogs than humans. Other studies have shown that tramadol may differ in concentration in the blood between different animals.
Overall, at least per these studies, this would result in a broad difference in analgesia between dogs. They would also imply some dogs need to have a much higher and more frequent dose than others. This makes it difficult to have standard dosing that will apply to all dogs. There have also been studies looking at how effective tramadol is in reducing pain– let’s discuss those next.
Is Tramadol a Good Painkiller for Dogs?
One of the largest studies collected information from various trials, totalling 848 dogs. Their calculations surmised that tramadol use probably meant less rescue pain relief (analgesic drugs given to stop immediate pain) was needed compared to the use of placebos or no pain relief. This indicates tramadol had at least some analgesic effect in these dogs. They found that tramadol performed better in this regard compared to drugs like buprenorphine and codeine, but worse than methadone and NSAIDs. They also noted that dogs on tramadol were almost as unlikely to need rescue pain relief as those dogs on multiple pain relief drugs. However, the study noted that their certainty of evidence (how likely the results were to be true) was low, as much of the collected evidence was likely to be biased or imprecise.
A smaller but more in-depth study compared the analgesic effects of methadone and tramadol on 28 dogs after orthopaedic surgery
They found that dogs given tramadol had higher mean pain scores when compared to high doses of methadone. This means that the dogs treated with tramadol were in more pain. It was also found that six dogs on tramadol needed rescue pain relief. (One dog on low dose methadone did, and none on high dose methadone). They concluded that methadone at high doses was a more effective analgesic than tramadol.
However, they did state that tramadol can provide ‘adequate’ pain relief at higher doses and when given as a rescue drug, showing again it has some effect. The study measured the level of Il-6 (a pro-inflammatory chemical that indicates acute pain) and found no significant increase in any dog after the study, possibly indicating adequate control of pain. Similarly, a study of 30 female dogs undergoing a spay following pyometra found that both morphine and tramadol can control pain when given pre-emptively. Though they did note that more anaesthetic gas was needed for dogs given tramadol compared to those on morphine.
However, other studies have demonstrated tramadol does not provide effective analgesia in real-world conditions
The study in Beagles concluded with “the non-opioid mechanisms of tramadol do not provide [pain relief] in this experimental setting.” A larger study of 35 dogs with clinical osteoarthritis compared carprofen (an NSAID), a placebo and tramadol. This study looked at both pain relief and the clinical improvement in mobility. It found that only carprofen showed an improvement in mobility. And carprofen had lower pain scores than tramadol or the placebo. They also noted that tramadol and the placebo had similar pain scores. This possibly indicates that tramadol didn’t have any actual analgesic effect in these dogs. However, of the four dogs requiring rescue pain relief, none were in the tramadol group, and one was in the carprofen group.
The study concluded by saying “tramadol… provided no clinical benefit for dogs with osteoarthritis”. It is important to note that pain scoring was performed by the owners, so there may be unconscious bias or mistakes.
It seems, therefore, that the evidence isn’t clear
Apparently, some dogs seem to have very good analgesia on tramadol, others have limited analgesia and others have none. This may be reflective of the difference in tramadol metabolism via enzymes between dogs, but few of the studies investigated this. It is also important to note that these studies have generally been very limited in numbers of dogs; and only focus on one type of pain. Some types of pain may respond better to tramadol than others.
One professor of anaesthesiology in the USA commented on the osteoarthritis study and mentioned that it may not be considering the emotional aspect of pain that tramadol, by influencing serotonin, may be affecting – they imply that tramadol may help prevent this emotional pain that results in animals withdrawing, not having happy lives and not recovering from injuries. Though there is no evidence to back their claims, it may shed some light on why many vets swear by tramadol, despite a lack of evidence. The professor also cleverly points out that “we don’t have any kind of proof that [tramadol] doesn’t work. We have a lack of evidence that it does work.”
What’s the Verdict?
Despite some quite scathing condemnations of tramadol in some studies, other studies seem to show at least some benefit to its use. Based on the evidence of how dogs metabolise tramadol, its relative safety, and the possibility that it can provide decent pain relief, it should be considered by veterinarians when dogs are in pain.
However, multiple studies advise that tramadol works best when given alongside other drugs like NSAIDs, paracetamol or gabapentin. This multi-modal approach to analgesia is always advised, as different drugs will act upon different components of pain, providing a broader analgesic effect than one drug alone.
The difficulty in giving tramadol to individual patients is how much bias and placebo effect is involved. Whether much of the perceived pain relief in actual patients in practice is a placebo or not remains to be seen; but should be addressed so animals are not left without pain relief needlessly. Many pain specialists therefore recommend that tramadol shouldn’t be used alone in case pain is still present but no longer perceived by the owner or vet.
In summary, dogs appear to have a varied metabolism of tramadol, resulting in a wide range of effects; but generally requiring higher and more frequent doses than in humans. Studies have shown tramadol has both some and no analgesic effect, which may be reflective of this varied metabolism. Tramadol is licensed and can be used, but care must be taken. For example, using it alongside other drugs, and close monitoring to minimise the placebo effect. Future evidence may support the professor of anaesthesiology in that tramadol may have hidden effects on emotional pain that does improve the analgesia and welfare of dogs.