Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed pharmaceutical classes in equine medicine. Used to help manage inflammation and pain, they are often viewed as harmless or relatively benign.
Yet it is well known and accepted that some of the most commonly used NSAIDs such as phenylbutazone (‘bute’, ‘PBZ’) and flunixin meglumine (‘flunix’) can cause gastric ulceration, irritation and bleeding, as well as have detrimental effects on kidney and liver function in susceptible horses and/or with long-term use.
These medications inhibit cyclooxygenase (COX) inflammatory pathways, resulting in decreased inflammation, swelling and fever. COX pathways can be further divided into COX-1 and COX-2, and historically we have attributed COX-1 being responsible for beneficial effects within the body. COX 1 is known to support normal protective mechanisms in the gastrointestinal (GI) system, kidneys and liver through the production of prostaglandins.
We’ve also historically viewed production of COX-2 to be ‘harmful’- attributing it to excessive inflammation, tissue damage and swelling. So surely, if we can produce NSAIDs that block COX-2 (significantly reducing inflammation), whilst sparring the protective effects of COX-1 then everything should work perfectly. The solution? Preferentially selective COX-2 inhibitors. Medications such as Firocoxib (Equioxx, Previcox) and Meloxicam (Metacam). Which in theory, fit the bill perfectly. The only thing is, the inflammatory process isn’t as simple as we once thought it may be….
Whilst excessive production of inflammatory mediators is largely viewed as harmful to the body, and NSAIDs certainly play an important role in veterinary medicine, it’s not quite as simple as blocking COX-2 production and expecting normal and healthy function and healing in our horses…
When it comes to COX-1 and COX-2, their roles aren’t neatly and distinctly separate. In fact, their activities overlap. Which means by using preferentially selective COX-2 inhibitors, we’re also unintentionally inhibiting protective mechanisms in our animals.
Research has shown that when preferentially selective COX-2 inhibitors are used for extended periods of time, and/or in doses that may be typically prescribed in practice, the ability of the medications to be selective decreases: that is, COX-2 inhibitors may result in spill-over to COX-1 pathways, resulting in similar effects to non-selective NSAIDs. This is really important if we’re considering using these drugs believing they are gentler on the digestive tract of our horses.
Preferentially selective COX-2 inhibitors may also adversely impact the gut microbiome, leading to digestive disturbances, changes in gut motility, compromised immune function, reduction in beneficial short chain fatty acid production, effects on fertility, behaviour, and ironically, may exacerbate low-grade inflammation long-term.
Research has now demonstrated that contrary to earlier belief, COX-2 actually plays a role in GI protective mechanisms, GI mucosal defence and repair. Particularly when an animal is injured, under systemic stress, or has existing damage to the GI tract (such as ulceration) the production of COX-2 is unregulated, to help facilitate healing. This is true in cases of gastritis, colitis and gastric ulcers. COX-2 contributes significantly to the resolution of gastrointestinal (GI) inflammation. By inhibiting the production of COX-2 in these circumstances, healing and recovery are further compromised. And if we think about it in a practical sense, the horse who is prescribed NSAIDs is generally in pain, stressed, ill, injured and/or on box (stall) rest- states where they are already at risk of gastric ulceration, before they are even prescribed NSAIDs. By further inhibiting the production of COX-2, we may be compromising their healing. Recent research has also demonstrated that the use of preferentially selective COX-2 inhibitors may also increase risk of renal injury in horses.
Ultimately, supporting our horses health, performance and healing requires us to look beyond simply suppressing clinical signs. Whilst NSAIDs have an important place in equine veterinary medicine, we must also consider the horse’s underlying health, gastrointestinal integrity, nutritional status and the factors that may be contributing to inflammation in the first place. We have opportunities to support our horses long before, during and after medication is required. Through optimising diet and feeding practices, supporting a healthy gut environment, and using carefully selected nutritional and herbal therapeutics, we can help promote gastrointestinal health, support the body’s natural inflammatory regulation and optimise the conditions needed for recovery and tissue repair.
Camilla Whishaw is a highly regarded, experienced horsewoman and naturopath, helping to holistically treat and manage a broad range of equine health conditions and injuries, with a passion for mare and stallion fertility.
As a world-renowned practitioner, presenter, author, and consultant in the field of Equine Naturopathy, Camilla shares her knowledge through keynote presentations, interviews, lectures, panel sessions, and workshop training.
