Research sparse on the painkilling performance of NSAIDs in horses – review

More clinical trials are needed to determine how well non-steroidal anti-inflammatory drugs (NSAIDs) perform as painkillers for horses with abdominal pain, according to the authors of a just-published review.

Gerardo Citarella and his fellow researchers, writing in the journal Animals, said the use of NSAIDs is an indispensable aid in the treatment of visceral disorders in horses with colic or post-castration abdominal pain.

NSAIDs act primarily by inhibiting COX enzymes, which play a role in inflammation. There are two forms, COX-1 and COX-2.

Over time, new molecules have been developed to limit NSAID-related side effects while preserving their painkilling and anti-inflammatory effects.

Recently, research has focused more on molecules targeting COX-2, which is responsible for the trigger of pain and inflammation in response to injury. These allow the functionality of COX-1, which is responsible for maintaining protective and reparative physiological mechanisms, to be preserved.

The review team, with the University of Zurich in Switzerland, said a recent study found that the most frequently prescribed NSAIDs for the treatment of colic in Britain, the United States and Canada were flunixin meglumine and phenylbutazone — both traditional non-selective NSAIDs.

Earlier studies delivered similar findings in South Africa.

The researchers said it was interesting to note that the prescribing trend is still formally linked to the use of traditional non-selective COX inhibitors, despite the availability of newer molecules such as meloxicam and firocoxib, which are designed to more specifically target the COX-2 isoform to avoid undesirable gastrointestinal side-effects.

This, they said, apparently derives from some scepticism towards the analgesic potency of some of the newer-generation NSAIDs, particularly firocoxib – an entirely COX-2-selective NSAID.

Considering the high rate of prescribing NSAIDs and their role in pain management in horses, it is crucial to understand the analgesic performance of the different classes of NSAIDs in this species, they said, with clinical practice guided by evidence-based research.

The researchers set out to identify, synthetise, and evaluate the evidence concerning the analgesic efficacy of NSAIDs available to treat abdominal pain in horses, and to establish, if possible, whether there is an NSAID that could provide better analgesia compared to others.

Research published between 1985 and the end of May 2023 was searched on three databases, PubMed, Embase, and Scopus.

A total of 10 studies met the inclusion criteria.

Risk of bias was assessed with a recognised tool, and the level of evidence was scored according to the Oxford Centre for Evidence-based Medicine.

From those 10 studies, a high risk of bias was identified due to the presence of selection, performance, and “other” types of bias — in most cases the absence of a validated pain score. Indeed, only one of the studies judged equine pain with a validated pain score.

“Therefore, caution is required in the interpretation of results from individual studies,” they said.

The authors found that, to date, the scientific evidence concerning the analgesic efficacy of NSAIDs in the treatment of abdominal pain in horses remains uncertain.

Evidence on whether any one NSAID may be more potent than another regarding the treatment of abdominal pain in horses is sparse.

“This systematic review showed that the current scientific literature cannot adequately justify the therapeutic choice of one NSAID over another for the treatment of abdominal pain in horses.”

More clinical trials are necessary to understand the painkilling performance of NSAIDs in such cases, they said.

The review team, discussing their work, said the studies that met their inclusion criteria involved a total of 184 horses in castration studies and 175 horses with colic.

“Despite the widespread use of NSAIDs worldwide and the lengthy research period examined (1989–2023), the total number of horses investigated seems relatively small.”

Concerning the interventions used, flunixin was the most common. It is, they said, still considered a sort of gold standard, against which the efficacy of other drugs can be compared.

“In theory, clinical interventions should only be used if they have been proven safe and effective in well-structured studies.

“However, this systematic review shows how evidence-based decisions often result from underpowered randomised studies and with unclear control of bias.

“Still, it is the clinicians who must decide whether they believe that the intervention should be used or not in clinical practice.”

The latter represents an interesting point, they said, as it appears that over the years the focus of NSAID scientific evaluation has changed its direction.

In fact, in the selected studies especially for colic pain, considerable attention was paid to the anti-inflammatory and pharmacological effects on the gut lining rather than on painkilling performance.

“However, clinically, the use of NSAIDs is primarily still aimed at achieving an expected analgesic effect rather than selecting the best NSAIDs with regard to COX selectivity.”

In conclusion, the review team said experimental studies have clearly shown that concerning mucosal interference, COX-non-selective NSAIDs are worse than COX-selective ones. However, COX-non-selective NSAIDs are still the most frequently used drugs in a clinical setting.

Evidence from available studies cannot yet adequately address the question: “What is the clinical efficacy of NSAIDs in terms of analgesia?”, they said.

For many of the studies, painkilling performance was not the main outcome but a secondary component of the research. Therefore, more clinical trials, focusing on addressing pain, with a validated easy-to-use pain score, are necessary to fully address the painkilling abilities of NSAIDs in the treatment of abdominal pain in horses.

The study team comprised Citarella, Vanessa Heitzmann, Elisabeth Ranninger and Regula Bettschart-Wolfensberger, all with the Section of Anaesthesiology, part of the Department of Clinical Diagnostics and Services within the Vetsuisse Faculty at the University of Zurich.

Citarella, G.; Heitzmann, V.; Ranninger, E.; Bettschart-Wolfensberger, R. Analgesic Efficacy of Non-Steroidal Anti-Inflammatory Drug Therapy in Horses with Abdominal Pain: A Systematic Review. Animals 2023, 13, 3447. https://doi.org/10.3390/ani13223447

The study, published under a Creative Commons License, can be read here.