SPORTS MEDICINE AND REHABILITATION Xylazine
Local administration of xylazine may be an option for managing pain in horses. In people, intra- articular administration of -2 agonists has been shown to mediate analgesia.49 Similarly, an equine study by Scicluna60 showed that xylazine offers analgesic benefits for horses when adminis- tered intra-articularly. However, an in vitro study evaluating xylazine administration at various con- centrations to equine cartilage explants showed dose-dependent chondrotoxicity.61 In people, peri- neural administration of -2 agonists with local anesthetics has also been shown to increase analge- sia compared to anesthetics alone.62 Therefore, perineural administration in the laminitic horse could be considered; however, intra-articular use in the horse should be performed with caution.
Local Anesthetics
Mechanism of action: Local anesthetics inhibit pain by blocking sodium channels, thereby interrupting neurotransmission near the site of injury.11 Local anesthetics prevent initiation and conduction of electrical impulses in C and A-delta sensory nerve fibers.63 They have also been shown to reduce post- synaptic depolarization mediated by NMDA recep- tors at the spinal cord in laboratory animals.64,65 This drug class has a long history of diagnostic and therapeutic use in the horse.
Lidocaine
The antinociceptive effects of systemic lidocaine have been evaluated in horses. In a study of con- scious, healthy research horses, CRI of lidocaine (2 mg/kg bolus followed by 50 g/kg/min CRI for 2 hours) significantly increased somatic pain (thermal threshold) and visceral pain thresholds.66 Clinical reports have also shown effective analgesia with the use of lidocaine CRI in horses with chronic lamini- tis.67 While not studied in the horse, IV lidocaine has also been established as having analgesic effects in human patients with neuropathic pain.67 In addition to blocking neurotransmission or af-
ferent signals, perineural administration of local an- esthetics have also been reported to cause a decrease in gene expression of inflammatory proteins.68 A suppression of inflammation with perineural an- esthesia has been suggested in humans and in lab- oratory animals,69 but has not been demonstrated in the horse. There is some controversy as to whether lidocaine has any anti-inflammatory effects in the horse.9
Transdermal administration of local anesthetics
are thought to have some local benefit over the site of injury,70 and it has been suggested that lidocaine patches could be applied over the digital nerves of laminitic horses for pain relief.11 A study of healthy, adult horses showed an increase in both thermal and superficial mechanical nociceptive thresholds after application of a 5% lidocaine patch
248 2020 Vol. 66 AAEP PROCEEDINGS
to the withers and saddle region. Analgesic effects were seen after product application and at 1 hour after the patch was removed.70 Percutaneous cath- eter placement over the palmar nerves has also been described in the horse to provide continuous nerve blockade. This allows treatment with lidocaine, mepivacaine, or bupivacaine.71
Liposomal Bupivacaine
Liposomal bupivacaine was developed and ap- proved for use in humans to help prolong the analgesic effects of the local anesthetic bupiva- caine.72,73 This formulation allows the slow re- lease of bupivacaine over time and is approved for infiltrative use in the dog and cat following specific procedures. It is estimated to provide up to 72 hours of pain relief.74 To date, two equine studies have been performed.
The first evaluated use of liposomal bupivacaine in the joint of healthy horses to assess possible chondrotoxic effects. Minimal effect on markers of chondrode- struction were found, suggesting that this medication can be administered in the joint safely.75 The second study looked at use of liposomal bupivacaine compared to standard bupivacaine administered perineurally (abaxial nerve block). Forelimb lameness was in- duced by inserting a screw into the sole. Objective lameness (inertial sensor system) and mechanical no- ciceptive thresholds were evaluated. Liposomal bu- pivacaine significantly improved objective lameness and mechanical nociceptive thresholds up to 24 hours after administration. The time of analgesia was greater for liposomal bupivacaine compared to stan- dard bupivacaine (analgesia for 1 hour only post- injection).76 This formulation of bupivacaine would be beneficial to provide the laminitic patient with lon- ger-lasting analgesia; however, a liposomal bupiva- caine formulation is not currently labeled for use in the horse.
Ketamine
Mechanism of action: Ketamine is an NMDA antag- onist and is used to help mitigate central sensitiza- tion that can occur with chronic pain.11 Ketamine has been shown to have a short duration of action; therefore, administration via CRI is strongly suggested.77 As mentioned previously, ketamine in combina-
tion with tramadol provided analgesia in horses with naturally occurring chronic laminitis.48 Au- thors report that the addition of ketamine resulted in significantly reduced limb off-loading frequency for the entire treatment period of 7 days. Signifi- cant reductions in TNF- and TXB2 (a stable me- tabolite of the vasoconstrictor prostanoid, TXA2) were also seen in the ketamine-tramadol group, which was not seen with oral tramadol alone.48 However, CRI of ketamine alone may not be ben-
eficial. One study looked at ketamine given to horses treated for a variety of conditions, including osteomyelitis, joint sepsis, burns, and colic.13 Ket-
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