amine CRI was given at 400 and 800 g/kg/hr for 5 days. Horses showed variable response with some horses showing no signs of comfort while others showed markedly increased comfort. However, pain was evaluated using only heart rate and a subjective comfort evaluation.13


Gabapentin


Mechanism of action: Gabapentin is used predomi- nantly for human and veterinary patients with chronic and neuropathic pain.78 Gabapentin me- diates analgesia by binding to the -2--1 subunit of voltage-gated calcium channels in the spinal cord and brain. It can then change the release of the neurotransmitters glutamate, GABA, and norepinephrine.79 Multiple case reports are available detailing suc-


cess with use of gabapentin in horses with neuro- pathic pain,78 including chronic laminitis,80,81 headshaking,82 and femoral neuropathy.78 How- ever, the reported bioavailability of gabapentin is low (16.2%).83 Therefore, high oral doses (5 to 20 mg/kg PO 2 to 3 times daily) are recommended.3 A recent study suggests even higher doses could be used in the horse. A single dose of gabapentin was administered to a group of 9 healthy horses at 10, 20, 40, 60, 80, 120, and 160 mg/kg in a randomized cross-over design. Plasma samples were taken up to 64 hours after administration. Horses were also evaluated for signs of sedation and ataxia. While plasma concentrations increased across the dose level, the increase was not in a proportional manner—the authors concluded that a dose higher than 120 mg/kg would not provide any noticeable differences in pharmacological effect. Only one horse showed signs of moderate sedation at the higher dosages (120 mg/kg and 160 mg/kg). How- ever, evaluation of hepatic and renal values was not performed and the authors comment that the safety of repeated dose administration higher than 20 mg/kg needs to be evaluated further.84 Gabapentin has been reported to be ineffective at reducing the degree of chronic lameness in the horse. In one study, horses with naturally occur- ring osteoarthritis in a variety of joints were given gabapentin orally at 5 mg/kg and 10 mg/kg q8h for 14 days. No significant improvement in lameness was seen for either group.80 In another report, no improvement was seen when gabapentin (20 mg/kg q12h PO) was added to treatment with phenylbuta- zone (4 mg/kg q12h PO) in a horse with severe lami- nitis. Authors also showed that the plasma concentrations were well below that reported to pro- vide analgesia in humans and treatment duration was limited to 2 days.81 It is likely that both an increased dose and duration of treatment are needed if gabapentin is to have efficacy in treating laminitic horses.


SPORTS MEDICINE AND REHABILITATION Epidurals


Mechanism of action: Epidurals allow administra- tion of analgesics at lower doses than those required for systemic administration. Morphine given alone (0.2 mg/kg) and when com-


bined with detomidine (30 g/kg) for experimentally- induced hindlimb lameness showed significantly re- duced lameness for up to 6 hours after administra- tion.85 In addition, horses that received this same drug combination via epidural before stifle arthros- copy had significantly reduced lameness and heart rates compared to controls.86 Hence it is possible that epidural morphine (alone or in combination with detomidine) might have a benefit for hind-limb laminitis. Efficacy of epidurals for horses with forelimb disease including laminitis remains a topic of debate. However, several studies suggest that there may be a benefit. For example, in a study of carpal synovitis induced with lipopolysaccharide in ponies, either a morphine (0.1 mg/kg diluted to 0.15 mL/kg with saline) or buprenorphine epidural (5 g/kg diluted to 0.15 mL/kg with saline) was admin- istered. A significant reduction in lameness was seen at 30 minutes with the morphine group and at 6 hours with the buprenorphine group, suggesting that morphine epidural was an effective analgesic for pain in the thoracic limbs.87


Vasodilators


Mechanism of action: Chronic laminitis is marked by aberrant vascular patterns and hemodynamic disturbances of lamellar tissues.88,89 Endothelin-1, a potent vasoconstrictor has been shown to have significantly increased expression in connective tis- sues during chronic laminitis as opposed to acute laminitis.90 While vasodilators have been used in the laminitic horse in an attempt to offset this dis- ruption, it is unknown if changes in blood flow con- sistently occur and help with healing or alleviate pain.


Pentoxifylline


Pentoxifylline is a rheologic agent4 that is thought to increase blood flow in compromised vasculature by increasing the malleability of blood cells.91 Vasodi- latory effects are mediated through increases in pro- duction of intracellular cyclic adenomonophosphate and nitric oxide.92,93 Pentoxifylline has been shown to have extremely variable absorption in the horse after oral administration.94,95 Bioavailabil- ity is also somewhat variable. In one study, healthy horses received 10 mg/kg pentoxifylline PO q12h for 8 days—bioavailability after the first dose was 68% and decreased to 44% after the last dose. Pentoxifylline has been shown to produce endothe- lium-dependent and endothelium-independent re- laxation of the equine digital veins. Pentoxifylline also mediates improvements in systemic microvas- cular flow and tissue oxygen delivery.92 Relaxation of the equine digital veins was shown in vitro92; however, use of pentoxifylline (4.4 mg/kg PO q8h for


AAEP PROCEEDINGS  Vol. 66  2020 249


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