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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The problem of brachycephalic dogs in New Zealand: Why has Trade Me banned some of them?

As of the 1 March 2018 ‘Trade Me’ New Zealand, our biggest online trading website, will no longer allow three brachycephalic dog breeds to be sold through their platform: Pugs, French Bulldogs, and British Bulldogs. This is a huge win for the welfare of these animals.

What are brachycephalic dogs?

The word brachycephalic literally breaks down to ‘short’ ‘head’. It refers to animals (it’s not just a dog problem!) with short faces/snouts. The classic example is the Pug – with its squishy face and big eyes. The Persian cat is another example. The muzzle, or snout, of these animals has essentially been reduced in length over time via breeding. It has become a desirable characteristic.

post 15 pug
The Pug is a good example of a brachycephalic dog breed

For many people, the attraction of these dogs is in their resemblance to babies or children. A small, round face makes them ‘cute’ and ‘adorable’. This factor is becoming even more important as many people are choosing not to have children, or delaying until later in life. Instead, their pet may play the role of this family member in their life.

What is wrong with these dogs?

The problem with breeding to reduce the length of these dog’s snouts/muzzles is what has happened as a result [1]. The bony structures of the head have reduced in size, but in most cases the soft tissue in the back of the mouth and throat has remained the same. This means these dogs have to breathe around this extra tissue. Other things have happened as a result of the bony changes:

  • The size of their nostrils is reduced – they are tiny! Many of these dogs’ struggle to get enough air through their nose and so resort to ‘open mouth’ breathing;
  • Their trachea, or airway, is too small for them. It is also very weak. They really have to work hard to get air into their lungs – sometimes they work TOO hard and their airway collapses. This is an emergency situation!

Overall, their breathing could be likened to trying to suck air through a thin drinking straw that has cloth over one end. Most of these dogs have to breathe with their mouth open, and snorts or snoring sounds result from the extra soft tissue in their mouth flopping into their airway.

This snoring sound may seem ‘cute’ to many people, but it actually means the dog is struggling to breathe properly! Their small airway and all that soft tissue in their mouth is making it very difficult for them.

These dogs get very hot in Summer and can often over-heat to the point of suffering from heat stroke – another emergency situation. Dogs in general cannot sweat as well as people. This means they rely on open-mouth breathing to cool them down. If a dog is not able to breathe very well, as is the case in these ‘brachy’ dogs, then this can be a problem. And again, if they work too hard breathing, their weak airways can collapse!

Other issues with these dogs include: their eyes bulge out of their skull resulting in dry eyes and sometimes ulcers; skin conditions and/or infections due to excess facial skin – all those rolls and folds are the perfect breeding ground for bacteria; and often these dogs struggle to give birth as puppies’ heads are too big for their mothers’ pelvic bones to pass through. Most British Bulldogs are delivered via caesarean section with the help of a veterinarian.

How has it got to this point?

Because so many people want these dogs, there are a lot of people breeding them. It is big business! One puppy can fetch thousands of dollars. But because dog breeding is unregulated in New Zealand, there are no rules about who can do it and how. As a result, people have kept breeding for what people want – short ‘cute’ snouts. Supply equals demand. The problem has got worse.

Not only this, but oftentimes breeding animals (the parents) are kept in poor conditions and become ‘breeding machines’. There are obviously exceptions to the rule, and voluntary members of organisations, such as Dogs NZ (formerly the New Zealand Kennel Club) are bound by self-imposed breeding regulations. However, many ‘backyard’ breeders of these dogs are less conscientious.

What can we do?

This move by Trade Me to stop these three breeds being sold on their platform has been celebrated by many animal welfare organisations and veterinarians. By stopping a major avenue for the sale of ‘backyard’ bred dogs, there is hope yet! This will stop unwitting puppy buyers from purchasing their pet ‘sight unseen’. Often these puppies are sent to them, or they collect them from a mutual meeting place, so that the breeding area and parents are not seen. These buyers have no idea what conditions the parents are in (what their purchase is supporting), or what the parents are like (a good indication of what their puppy may be like).

However, as the New Zealand Veterinary Association (NZVA) has proposed, there are still things that can be done. Their webpage has a list of additional information and their companion animal spokesperson, Rochelle Ferguson, has written a Spinoff feature with advice. To summarise, before adopting prospective owners should:

  • Consider adopting a dog from a shelter, rather than buying one that may be supporting poor breeding practise;
  • Visit the breeder and meet the parents of the puppy they are considering adopting;
  • Support breeders who screen for inherited diseases and who don’t breed puppies with these extreme features;
  • Ask about the mother’s health and whether a caesarean was needed;
  • Consider whether the mother’s (and other dogs) behavioural needs are being met by the breeder. This all affects the puppy.

In the future:

  • Regulations that require people to have a license to breed and sell puppies would be beneficial;
  • Sales on premises (and not ‘sight unseen’ or online) could be a requirement.

I will conclude by quoting Rochelle’s message:

“The fallout from puppies that have been irresponsibly bred is shouldered, not by the breeders who profit from their sale, but by the families that purchase these animals and the veterinarians that treat them.”

References
  1. Packer, R.M.A., et al., Impact of Facial Conformation on Canine Health: Brachycephalic Obstructive Airway Syndrome. Plos One, 2015. 10(10).