Pain management for laminitis in the horse

The inability to control pain is the most common reason for cessation of treatment and euthanasia in cases of laminitis, yet pain also serves a unique protective function in these cases, particularly in the acute phase when lamellar integrity is weakened. Successful analgesia requires an understanding of the disease pathophysiology, the sources of pain in laminitis, methods of serial pain evaluation, and methods of analgesia including systemic and regional techniques. This review discusses the approach to analgesia including detail of traditional and novel analgesic medications and techniques with specific reference to the laminitis case.     

Current research and theories on the pathogenesis of acute laminitis in the horse

A large number of studies have been undertaken in recent years aimed at furthering our understanding of the complex mechanisms underlying the common and debilitating condition of acute laminitis in the horse. Many of these studies have either reinforced or cast doubt on previously held theories on the pathogenesis of this disease, while others have suggested new mechanisms which may play a key role in its development. This review seeks to put the current hypotheses into the context of this recent body of evidence. While a unifying theory may not yet seem to be achievable, this review demonstrates that most of the current theories are not mutually exclusive. Studies utilising in vitro and in vivo models of the disease, particularly addressing the areas of inflammation, haemodynamic disturbances and enzyme activation in the hoof, as well as the preceding events occurring in the hindgut, have helped to explain many clinical observations of the disease and may possibly lead to more effective therapies and means of prevention in the future.     

Unilateral white line disease and laminitis in a quarter horse mare

A 5-year-old quarter horse mare presented with unilateral, severe, chronic forelimb lameness. Radiographs revealed extensive hoof wall separation and capsular rotation of the distal phalanx. Treatment included dorsal hoof wall resection, phenylbutazone, a bar shoe, and stall rest. Whether white line disease or laminitis was the primary lesion remains unclear.     

Disseminated intravascular coagulation in a horse with postpartum ulcerative colitis and laminitis

Hemostatic studies were conducted on a five year old Belgian mare presented two days postpartum with colic and laminitis that was unresponsive to treatment.

The mare was moderately thrombocytopenic with plasma fibrinogen levels more than twice that of a normal control horse. Platelet function as evaluated by aggregometry indicated that the circulating platelets were markedly hyporesponsive. Activated partial thromboplastin times and prothrombin times were prolonged. Para-coagulation tests (protamine sulfate and ethanol gelation) were strongly positive and fibrin degradation products were significantly elevated in the serum.

The laboratory data suggested that the clinical bleeding was the result of the development of disseminated intravascular coagulation. The data were compatible with intravascular activation of the clotting mechanism, consumption of hemostatic factors, inhibition of platelet function and enhanced stimulation of the fibrinolytic mechanism.

This report illustrates the complexity of the hemostatic abnormalities associated with pathological overactivation of the hemostatic mechanism. Factors such as tissue thromboplastins and/or endotoxins can stimulate disseminated intravascular coagulation, particularly during pregnancy or in the early postpartum period when a physiological “hypercoagulable” state already exists.

     

Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis

HistoryA 4‐year old, 500 kg Thoroughbred female horse diagnosed with bilateral forelimb laminitis and cellulitis on the left forelimb became severely painful and refractory to non‐steroidal anti‐inflammatory therapy (flunixin meglumine on days 1, 2, 3 and 4; and phenylbutazone on days 5, 6 and 7) alone or in combination with gabapentin (days 6 and 7).Physical examinationPain scores assessed independently by three individuals with a visual analog scale (VAS; 0 = no pain and 10 = worst possible pain) were 8.5 on day 6, and it increased to 9.5 on day 7. Non‐invasive blood pressure monitoring revealed severe hypertension.ManagementAs euthanasia was being considered for humane reasons, a decision was made to add an experimental new drug, trans‐4‐{4‐[3‐(4‐Trifluoromethoxy‐phenyl)‐ureido]‐cyclohexyloxy}‐benzoic acid (t‐TUCB), which is a soluble epoxide hydrolase (sEH) inhibitor, to the treatment protocol. Dose and frequency of administration were selected based on the drug potency against equine sEH to produce plasma concentrations within the range of 30 nmol L^?1 and 2.5 μmol L^?1. Pain scores decreased sharply and remarkably following t‐TUCB administration and blood pressure progressively decreased to physiologic normal values. Plasma concentrations of t‐TUCB, measured daily, were within the expected range, whereas phenylbutazone and gabapentin plasma levels were below the suggested efficacious concentrations.Follow upNo adverse effects were detected on clinical and laboratory examinations during and after t‐TUCB administration. No new episodes of laminitis have been noted up to the time of writing (120 days following treatment).ConclusionsInhibition of sEH with t‐TUCB was associated with a significant improvement in pain scores in one horse with laminitis whose pain was refractory to the standard of care therapy. No adverse effects were noticed. Future studies evaluating the analgesic and protective effects of these compounds in painful inflammatory diseases in animals are warranted.     

Expression of endothelin in equine laminitis.

Biosynthesis of endothelin-1 (ET-1), the most potent endogenous vasoconstrictor yet identified, is increased following myocardial infarction (MI) in man. Pathological events which occur in the connective tissues of the equine hoof during laminitis are similar in some respects, to changes occurring in the myocardial connective tissues following MI in man. The objective of this study was to determine whether ET-1 expression in connective tissues obtained from the hoof of laminitic horses is increased compared with tissues obtained from healthy horses. Expression of ET-1 in connective tissues of the equine hoof was measured following tissue extraction from 3 groups of horses: horses in which acute laminitis had been induced by the administration of starch; chronically foundered horses; nonlaminitic horses. The concentration of ET-1 in laminar connective tissues obtained from all laminitic horses (1573.0 +/- 392.8 pg/g of tissue; n = 10) was increased when compared with tissues obtained from nonlaminitic horses (392.5 +/- 117.4 pg/g of tissue; n = 5) (P<0.05). The concentration of ET-1 in laminar connective tissues obtained from the experimentally induced, acute laminitic horses (1043.6 +/- 254.4 pg/g of tissue; n = 7) and from the spontaneously affected, chronic laminitic horses (2808.3 +/- 878.6 pg/g of tissue; n = 3) was increased compared with the control group (P<0.05, P<0.01, respectively). The concentration of ET-1 in laminar connective tissues obtained from the chronic laminitic horses was greater than that of the experimentally induced, acute laminitic group (P<0.05). It is suggested that the data provide a strong argument that increased ET-1 expression in the connective tissues of the equine hoof represent a potentially important and hitherto unrecognised component of the pathophysiology of equine laminitis. Further studies are needed to determine whether inhibitors of ET-1 converting enzyme or antagonists of ET-1 receptors might be useful in the treatment and prevention of laminitis in horses.     

The pathophysiology of developmental and acute laminitis.

This review implies that although we know more regarding the enigma of developmental and acute laminitis today than previously, there is still more to investigate. As these investigations are conducted and interpreted, new and more effective preventive and therapeutic regimens are likely to be developed, tested, and made available. As this occurs, the impact of laminitis should undoubtedly decrease. Unfortunately, due to the lack of clinical symptoms in the developmental phase and the shortness of the acute phase, it is also evident that the two sequelae of acute laminitis, subacute and chronic laminitis, are likely to continue to pose a major problem for some time.     

Treatment of acute laminitis. Supportive therapy.

Over the last decade, both the farriery and veterinary professions have greatly increased their collective experience and understanding of the treatment of acute laminitis. Many horses that would have not been considered candidates for treatment 10 to 15 years ago are now saved, and some progress to successful careers as athletes. Unfortunately, the difficulties over prediction of the course of the disease persist, which continues to complicate treatment decisions. By its nature, supportive therapy is designed to make the horse more comfortable and limit further laminar injury by countering adverse biomechanical forces. Therefore, the success of treatment depends on the degree of instability between the distal phalanx and the hoof when treatment is started as well as the effectiveness of medical and supportive therapy.     

Factors involved in the prognosis of equine laminitis in the UK.

The significance of clinical and radiological parameters as prognostic indicators for laminitis, 'founder' and 'sinking syndrome' was studied using case records of 216 horses and ponies. Five animals were destroyed without treatment and were not included in the results of the study. One hundred and sixty-two (77%) animals returned to athletic soundness; 7 animals (3%) did not regain full athletic function, 42 animals (20%) died or were destroyed. Cases were assigned to 4 groups on the basis of initial clinical examination alone. These groups were laminitis, acute founder, 'sinker' and chronic founder. This grouping was found in itself to be the most important prognostic parameter which was studied. Stepwise regression analysis of the data from animals by group indicated that the radiological measurement of founder distance, was the most significant radiological prognostic measurement for acute founder cases. Less significant prognostic parameters were the severity of lameness, rotation angles, the presence of solar prolapse, and the number of feet affected. The height of the animal at the withers was not significantly related to outcome. The prognosis for horses was not significantly different from that for ponies.     

Botulism in the horse.

Botulism should be considered in cases where weakness, paralysis, or intolerance to exercise might be seen in the horse. Dysphagia may also be present, although it is not a consistent finding. Potential sources include carrion in hay, moldy or otherwise rotted vegetation or forage, birds carrying material from animal burial or other similar sites, and contaminated carcasses on-site. Horses, especially foals, may also suffer from toxicoinfectious botulism, a condition where the C. botulinum might colonize and produce toxin within the gastrointestinal tract. Wounds also may harbor the organism and otherwise promote botulism. Diagnosis of botulism is often a clinical diagnosis backed up by elimination of other possible infectious, injurious, or toxic causes of weakness of the horse. Definitive diagnosis and type identification in the laboratory are difficult and usually require a suitable sample of the source material. Treatment often is unrewarding unless a case is identified early and the proper antitoxin is readily available. Prevention involves common sense approaches to feeding and care of the horse and, where possible, judicious use of vaccination in endemic areas.