or gaskin, mean serum fentanyl concentrations were consistent with those reported to be analgesic in other species (1 ng/mL) by 1 hour of application. This level was maintained until 32 hours after patch application with no hematologic or clinical side effects.38 Another study looked at fentanyl patches admin-


istered to client-owned horses suffering from a vari- ety of soft tissue or orthopedic conditions (including laminitis). All horses were thought to be refractory to NSAIDs (phenylbutazone or flunixin). Serum fentanyl concentrations of 1 mg/mL were measured 14 hours after patch application on the antebra- chium and stayed at this level for 18 hours post- application. However, while pain scores were improved in the horses, lameness scores were not significantly improved.39 In another report of sub- jective pain assessment in a group of hospitalized horses, only slight improvement in horses with lami- nitic pain was noted as opposed to significant im- provement in horses with visceral pain.40 It is worth noting that when given intravenously, fentanyl has been shown to provide ineffective anal- gesia with undesirable behavioral effects in adult horses.41,42 A study of conscious, standing horses tested visceral and somatic pain using duodenal/ colorectal distention and thermal thresholds, re- spectively. Fentanyl was administered as a CRI at four doses (8, 16, 32, 64 ng/kg/min). Control horses received either xylazine (positive control) or saline (negative control). None of the fentanyl groups showed a significant increase in visceral pain threshold following administration, while horses receiving xylazine showed a significant increase. A trend toward increased somatic threshold was seen 15 minutes after fentanyl CRI was initiated, but only in the highest fentanyl group.42 Based on these data, it appears that there is more benefit to treating pain in the laminitic horse with transder- mal as opposed to IV administration.


Methadone


Methadone administration has not been evaluated in the laminitic horse. As with other opioids, the dosage of methadone must be chosen carefully—side effects including spontaneous locomotion (0.2 mg/ kg), ataxia (0.5 mg/kg), and muscle tremors (0.5 mg/kg) have been seen.43,44 In a study of healthy horses, methadone administered at 0.2 mg/kg IV alone showed no significant analgesic effects, as de- termined by thermal and electrical nociceptive thresholds. However, when combined with detomi- dine (0.1 mg/kg IV), a synergistic effect was seen with significant increases in thermal and electrical nociceptive thresholds. This improvement in anal- gesia was also greater with both methadone and detomidine than with detomidine alone.43 There- fore, administration of methadone could be consid- ered in combination with detomidine for treatment of acute pain.


SPORTS MEDICINE AND REHABILITATION Tramadol


Tramadol has been shown to have poor oral bioavail- ability and rapid elimination in horses.45 It has, however, been shown to dose-dependently improve pain in horses with chronic laminitis. Analgesia was reported at a dose of 10 mg/kg (not seen at 5 mg/kg) q12h.11 However, signs of colic have been reported in horses at the 10 mg/kg dosage.46,47 Interestingly, when tramadol was administered in conjunction with a ketamine CRI, oral tramadol was more effective at a lower dose in a laminitis model. Dose administration included ketamine at 0.6 mg/ kg/hr for 6 hours/day for 3 days and oral tramadol at 5 mg/kg q12h for 7 days. Significant improvement in comfort level was reported.48


-2 Agonists


Mechanism of action:-2 adrenergic or adrenorecep- tor agonists mediate analgesia by decreasing affer- ent activity and activating descending inhibitory neurons.11 -2 receptors are found on primary af- ferent terminals in peripheral and spinal nerve end- ings, the dorsal horn of the spinal cord, centrally in the brainstem, and peripherally in the joint—their activation can produce central and peripheral anal- gesia.10,49 -2 agonists also have a synergistic ef- fect with opioids in both horses and humans, allowing an opioid-sparing effect.50–54 While effec- tive analgesics when given systemically, -2 adren- ergic agonists cause sedation, cardiopulmonary depression, and may influence gastrointestinal func- tion that may impact duration of their use.55 Al- ternate routes (e.g., epidural, intra-articular) are therefore sometimes suggested as alternatives.


Detomidine


Antinociceptive effects of -2 agonists in the horse have been well demonstrated,56,57 but controlled studies in the laminitic horse are lacking. For other forms of musculoskeletal pain, detomidine has been shown to be an effective analgesic. In one study of induced hoof lameness, detomidine given at 10, 20, or 40g/kg IV effectively raised the mechan- ical hoof pain threshold and lowered the intensity of hoof withdrawal response. This analgesic effect lasted for 55 minutes (mechanical hoof pain thresh- old) and 120 minutes (hoof withdrawal response). Lameness, as assessed by the modified Obel scale, was also significantly reduced at 20- and 40-g/kg doses.58 In a study of horses with naturally occur- ring forelimb or hindlimb lameness, horses that re- ceived 0.007 mg/kg detomidine IV alone or in combination with butorphanol (0.007 mg/kg IV) showed significant increases in mechanical nocicep- tive thresholds proximal to the coronary band up to 30 minutes after administration. Small, but signif- icant improvements in lameness, as measured by an inertial sensor system, were also seen.59


AAEP PROCEEDINGS  Vol. 66  2020 247


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