Pain management in horses
There are numerous NSAIDs licensed for use in the horse, with mechanism of action (COX selectivity), analgesic and anti-inflammatory efficacy, formulation, palatability and dosing frequency varying between products. Treatment choice therefore requires vets to be aware of these differences and assess case requirements on an individual basis.
Non-steroidal anti-inflammatory drugs act by inhibiting cyclooxygenase enzymes (COX). There are 2 isoforms of COX; COX-1 is traditionally associated with many important house-keeping functions within the body, such as maintaining the integrity of the gastrointestinal mucosa or blood flow to the kidneys. Whilst COX-2 is predominantly induced when inflammation occurs, although some expression in healthy tissues has been reported. Reported side effects of NSAID administration in the horse include gastric ulceration, right dorsal colitis and renal injury and these have been attributed to suppression of constitutively expressed COX.
Traditional NSAIDs such as phenylbutazone are not COX selective – they inhibit both enzymes to a similar extent. More recently, COX-2 preferential NSAIDs have been developed, with the aim of limiting the side effects associated with NSAID treatment. In the UK, meloxicam is the most commonly used COX-2 preferential NSAID in the horse, although other COX-2 selective NSAIDs such as fibrocoxib are also available. Clinical studies in horses have shown that oral meloxicam has fewer negative effects on the permeability of the gastric mucosa than phenylbutazone (D’Arcy-Moskwa et al 2012) and that oral meloxicam was not associated with the same reduction in blood albumin concentration that was seen following 13 days administration of phenylbutazone (Noble et al 2012).
There are also differences in the anti-inflammatory effects of the available NSAIDs, as demonstrated in recent studies of experimentally induced acute synovitis in the horse. Oral administration of meloxicam significantly reduced inflammatory mediators such as substance P and matrix metalloproteinase activity within synovial fluid (de Grauw et al 2009), whilst a similar reduction in these mediators was not observed in horses treated with phenylbutazone (de Grauw et al 2014). These studies also showed that meloxicam reduced inflammation-induced cartilage breakdown, which phenylbutazone did not. This suggests that meloxicam is a good choice for the treatment of acute inflammatory orthopaedic conditions.
Few studies comparing the analgesic efficacy of the available NSAID products have been published. In a recent blinded study of 77 horses with chronic lameness, meloxicam was shown to have equivalent analgesic efficacy to phenylbutazone (Olsen et al 2016). However it appears that analgesic efficacy may depend on the inciting cause of orthopaedic pain, with meloxicam demonstrating superior efficacy to phenylbutazone in a model of acute synovitis, but not in a model of mechanical lameness (Banse et al 2017).
In addition to clinical efficacy, there are other practical considerations that contribute to choice of analgesic product. Ease of administration and patient compliance are important to guarantee effective treatment. Palatability has been an issue, particularly with traditional phenylbutazone preparations. However some of the newer products are apple flavoured and are more readily consumed. Drugs that require once daily dosing such as meloxicam may be more convenient and better tolerated than others that require dosing more frequently such as phenylbutazone or suxibuzone. Oral NSAIDs are available as pastes, oral suspensions or granules for the horse. Pastes are advantageous if the horse will not consume the product voluntarily, however both pastes and oral suspensions are generally associated with greater expense than granule formulations. This often precludes their use long-term. There are now phenylbutazone, suxibuzone, flunixin and most recently meloxicam granules available in the UK for the horse.
In competition horses the detection time is often an important determinant in treatment selection. This varies considerably between different drugs and is significantly longer for phenylbutazone/suxibuzone than other actives ingredients. Clinicians also need to be mindful of legal requirements for documenting administration of phenylbutazone, as failure to ensure the declaration within the horse’s passport is signed at the time of administration, can result in prosecution and a significant fine. Using alternative NSAID products relieves this responsibility and may be a preferable if the horse’s passport is not available.
Over the past few years several new studies have been published, which have enhanced our knowledge of equine NSAID treatment options. With the availability of different products and new formulations, the clinician now has an armoury of therapeutic options which can be critically evaluated.
References
Effects of meloxicam and phenylbutazone in equine gastric mucosa permeability. (2012) D’Arcy-Moskwa, E., Noble, G.K., Weston, L.A., Boston, R., Raidal, S.L. J Vet Intern Med 26(6);1494-9.
Pharmacokinetics and safety of single and multiple oral doses of meloxicm in adult horses. (2012). Noble, G., Edwards, S., Lievaart, J., Pippia, J., Boston, R. and Raidal, S.L. J Vet Inetern Med 26(5):1192-201
In vivo effects of meloxicam on inflammatory mediators, MMPS activity and cartilage biomarkers in equine joints with acute synovitis. (2009) de Grauw, J.C., van de Lest, C.H., Brama, P.A., Rambags, B.P., van Weeran, P.R. Equine Vet J 41(7) 693-9.
In vivo effects of phenylbutazone on inflammations and cartilage-derived biomarkers in equine joints with acute synovitis. (2014). de Grauw, J.C., van Loon, J.P., van de Lest, C.H., Brunott, A. and van Weeran, P.R. Vet J 201(151-6.
The palatability and comparative efficacy of meloxicam oral suspension for the treatment of chronic musculoskeletal disease in horses. (2016) Olsen, M.E., Nagel, D., Custead, S., Wise, W., Penttila, K., Burwash, L., Ralston, B., Schatz, C. and Matheson-Bird, H. J Equine Vet Sci 44;26-30.
Comparative efficacy of oral meloxicam and phenylbutazone in 2 experimental pain models in the horse. UCVM Class of 2016, Banse, H. and Cribb, A.E. (2017) Can Vet J 58(2);157-167.