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Does tramadol work in dogs with chronic arthritis? | VETgirl Veterinary Continuing Education Blog

In this VETgirl online veterinary continuing education blog, we review the use of tramadol in dogs. Does it work? Well, you may have heard over recent years that tramadol has been put on the hot plate, receiving much attention for its role as an analgesic in canine patients. The reason for doubting tramadol’s pain relief properties stems from the pharmacokinetics of the drug and differences between human and canine pain receptors. Tramadol is a weak pure-mu opioid agonist. It is metabolized to O-desmethytramadol, which is the metabolite responsible for tramadol’s ability to inhibit the reuptake of noradrenaline and serotonin in nerve endings, thus making these two neurohormones more available to continue blocking pain signals. However, dogs produce very little of this active metabolite. Perhaps this difference in metabolism is why clinicians have trended towards recommending higher doses of tramadol (doses ranging from 1 to 10 mg/kg). Previous studies have been complicated by a placebo effect when measuring analgesic outcomes, and the placebo effect is a difficult bias to overcome when creating a study design. So, Budsberg et al out of University of Georgia (Go, Dawgs!) wanted to evaluate tramadol as an analgesic in the treatment of chronic osteoarthritis in a study entitled Lack of effectiveness of tramadol hydrochloride for the treatment of pain and joint dysfunction in dogs with chronic osteoarthritis. in this study, the authors aimed to evaluate objective measurements of pain relief in orthopedic dysfunction associated with tramadol use in dogs suffering from osteoarthritis.

This was a randomized, blinded, placebo and positive-controlled crossover study (e.g., really well designed, in VETgirl's opinion). Client-owned dogs were included in the study if they exhibited elbow or stifle dysfunction and signs of osteoarthritis-associated pain between the timepoints of January 2015 and May 2017. Dogs were excluded from the study if they received corticosteroids or polysulfated glycosaminoglycans ≤30 days prior to the study or at any timepoint during the study. Dogs were also excluded if they had joint surgery within the prior 12 months, systemic disease, disease affecting joints other than osteoarthritis, and osteoarthritis affecting joints other than the stifles or elbows. Each dog received a baseline physical examination, CBC, serum biochemical analysis, urinalysis, and radiographs of the painful joint to document osteoarthritis. If the patient exhibited osteoarthritis in multiple joints, the most clinically affected joint was selected as the joint of interest. All dogs received each of the three treatments: lactose powder as a control, carprofen at a dose of 2.2 mg/kg every 12 hours and a placebo control at midday, and tramadol hydrochloride at 5 mg/ kg every 8 hours. Each dog also had a 7-day washout period between each different treatment group.

Dogs received their blinded treatment three times daily by their owners. Owners were provided the blinded treatments in identical vials (and identical capsules, which was created by the pharmacy) and told to administer the medications orally for 10 days. They were also given codeine-acetaminophen as a rescue medication to give every 8 hours if they perceived their pet’s pain control was inadequate (e.g., if "unacceptable signs of pain" were seen); they chose this drug since it wasn't an NSAID and had a short duration of action. BTW, as a toxicologist, yes, it's ok for dogs to get Tylenol Codeine (e.g., acetaminophen or paracetamol). Dogs could be removed from the study if they exhibited an intolerance to the medication, if their level of pain control was unacceptable, or if they developed an interfering condition during the study time period. They then measured vertical ground reaction forces (specifically looking at vertical impulse [VI] and peak vertical force [PVF] and Canine Brief Pain Inventory (CBPI) scores, but this is way over the head of VETgirl as we don't do force plate stuff, so you'll actually have to read the article for more details on this. At any rate, the authors measured a baseline measurement (e.g., before pharmacological intervention or placebo) and at the end of each treatment period.

A total of 35 dogs completed the study. Eleven (31%) of dogs had osteoarthritis of the elbow joint, and 24 (69%) had osteoarthritis of the stifle. Only 4 dogs in the study required rescue medication. Interestingly, 3 of the 4 dogs requiring rescue pain relief were in the placebo portion of their study treatment. The fourth dog was in the carprofen section. Vertical impulse scores (VI) and peak vertical force (PVF) scores did not differ between baseline and day 10 of treatment for the tramadol and placebo groups, but the carprofen group did show increased VI and PVF scores. This objective data was similar to their trends in pain scores. The carprofen group showed smaller pain scores compared to the tramadol and placebo groups, and the tramadol and placebo groups were equivocal in pain scores.

So, what should we take away from this VETgirl podcast?

Results of this study suggest that tramadol does not provide improvement in orthopedic dysfunction, nor does it improve pain scores when used for treating canine osteoarthritis. Carprofen showed improvement in both orthopedic dysfunction testing and in pain assessments. Despite the fact that both tramadol and carprofen have short half-lives in dogs, there is a possibility that this study design was limited by a carryover effect from one treatment to the next within each dog, but the investigators implemented a washout period between treatments to limit this possible effect. An undisclosed number of individual dogs did show improvements in all scores while on tramadol, but not enough individuals to produce any statistical significance for the tramadol group compared to the placebo treatment group. In conclusion, the authors advise that tramadol is not an effective analgesic as it does not provide improvement in orthopedic dysfunction, nor does it provide improvement in pain for dogs suffering from elbow or stifle osteoarthritis. They further surmise that it is unlikely to help with osteoarthritis pain and dysfunction in other joints.

The takeaways and pros and cons of this study? First, this was a well designed study, as it was prospective, blinded, randomized and a positive-controlled crossover study, which we rarely see in veterinary medicine. The cons? There are some who believe that force plate analysis may have a lot of variability in dogs. More importantly? Our takeaway is that while tramadol is very safe and benign, it's likely not doing much and anti-inflammatories and other analgesics are likely warranted with any acute or chronic pain!

Abbreviations:
VI = vertical impulse
PVF = peak vertical force

References:
1. Budsberg SC, Torres BT, Kleine SA, et al. Lack of effectiveness of tramadol hydrochloride for the treatment of pain and joint dysfunction in dogs with chronic osteoarthritis. J Am Vet Med Assoc 2018;252(4):427-432.

2. Brown DC, Boston RC, Farrar JT. Comparison of force plate gait analysis and owner assessment of pain using the Canine Brief Pain Inventory in dogs with osteoarthritis. I Vet Inter Med 2013;27:22-30.

3. Stejskal M, Torres BT, Sandberg GS, et al. Variability of vertical ground reaction forces collected with one and two force plates in healthy dogs. Vet Comp Orthop Traumatol 2015;28(5):318-322.

3 thoughts on “Does tramadol work in dogs with chronic arthritis? | VETgirl Veterinary Continuing Education Blog

  1. Very interesting study. We commonly combine carprofen and tramadol as a treatment for chronic pain, but I wouldn’t have thought these results would show the carprofen by itself can be adequate.

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