A novel formulation for small animal arthritis?

When cats and dogs are in need of long-term/‘chronic’ pain relief we try to give them NSAIDs (non-steroidal anti-inflammatory pain relief). This is because NSAIDs have the most scientific evidence supporting their analgesic (‘pain-relieving’) effect and, unlike morphine, are able to be given orally as ‘take-home’ medications. Carprofen and meloxicam are just some examples of NSAIDs used in dogs and cats.

Veterinarians are scientists and have a responsibility to make evidence-based (i.e. using results from published studies in peer-reviewed journals) decisions on how to treat our patients. This means it is somewhat unethical to use or prescribe medications with very little evidence that they actually work. One such drug is tramadol. Tramadol is often used in cats and dogs where NSAIDs are contraindicated (e.g. kidney disease or gastrointestinal problems), or in combination with NSAIDs for ‘added effect’. It is an opioid agonist, however evidence for its analgesic effect is controversial. It may not actually be relieving pain, but instead just sedating animals so that they are not able to show signs of pain. The SkeptVet does an excellent job of reviewing Tramadol for Pain in Dogs and Cats and at one point suggests “The evidence is strong enough that tramadol should not be relied on as a sole or first-line analgesic.”

If this is the case, then what can we use in those animals where we might not want to give NSAIDs? Pain is a significant animal welfare issue. There is a reason it ranks highly in animal welfare assessment scales and evaluations. We have an ethical responsibility to treat it. The old adage of ‘if they are in pain they aren’t moving and so won’t do any more damage to themselves’ is not acceptable.

A recent publication in BMC Veterinary Research may shed some light on the future of chronic pain relief – by introducing a novel composite formulation [1]. This article is open access (free) online and can be found here. The authors argue that osteoarthritis treatment should “reduce inflammation, minimise pain, and maintain joint function.” They therefore propose the use of palmitoylethanolamide (PEA) in combination with quercetin in models of osteoarthritic pain and inflammation.

PEA is an endogenous (produced normally in the body – therefore has reduced risks of side-effects) fatty acid amide produced by tissues in response to acute inflammatory and painful conditions, but decreased in chronic conditions. There is evidence already for its anti-inflammatory and analgesic effects in some other conditions, but the authors wanted to explore whether it would help with osteoarthritis. PEA is an endocannabinoid (i.e. binds to cannabinoid receptors in the body). The authors combined it with quercetin, a natural antioxidant, as PEA is rapidly oxidised in the body. They compared this combination to the NSAID meloxicam as their ‘benchmark’ drug.

They used two different rat models of inflammatory and osteoarthritic pain: by causing paw oedema; and inducing osteoarthritis. The first step of the experiment involved giving the different treatments being tested ‘pre-emptively’ (i.e. before they did anything to the rats). This way they could see if it actually worked to reduce pain and inflammation before moving onto the second step. In this second step they used it ‘therapeutically’ three times a week to see if it would work clinically on osteoarthritis.

The results show that their ‘PEA-Q’ combination decreased inflammatory and hyperalgesic (increased sensitivity to pain) responses by:

  • Reducing oedema in the rats paw
  • Decreasing an inflammatory score used in histology (microscopic structure of tissues)
  • Reduced activity of a marker of inflammatory cell infiltration
  • Decreased thermal/heat pain sensitivity

These effects were better using their novel drug combination – compared with using the NSAID.

In their osteoarthritis model they found the combination:

  • Reduced mechanical allodynia (triggering of a pain response from stimuli which do not normally provoke pain)
  • Improved locomotor function
  • Protected the cartilage from damage

These effects were equal to or better than the NSAID treatment.

These are exciting results for anyone trying to manage long-term pain in dogs and cats as the authors have now moved to translate these findings to canine and feline osteoarthritic pain. Watch this space!

{The author would like to acknowledge Adrienne French for feedback on the draft of this post.}

References

  1. Britti, D., et al., A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models. BMC Vet Res, 2017. 13(1): p. 229.

 

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