Semester of Graduation

Spring 2022

Degree

Master of Science (MS)

Department

Veterinary Clinical Sciences

Document Type

Thesis

Abstract

Opioid drugs have the potential of provide local analgesia in inflamed joints. To date, morphine is the only opioid that has been tested for intra-articular (IA) administration in horses. Having an alternative drug, other than morphine, could widen the therapeutic options, particularly in cases of drug shortages or inaccessibility to specific drugs. The work presented in this dissertation reports the cytotoxic effects of buprenorphine on cultured equine chondrocytes, and the pharmacokinetic, pharmacodynamic and analgesic effects, of IA administered buprenorphine in horses with experimentally induced synovitis.

To evaluate the potential cytotoxic effects on equine cartilage, chondrocytes were obtained from normal equine joints and cultured. Chondrocytes were exposed to two concentrations of buprenorphine (0.05 mg mL-1 and 0.12 mg mL-1) for 0 and 2 hours. Chondrocyte viability was evaluated after the exposure using four different techniques.

For the pharmacokinetic, pharmacodynamic and analgesic assessment of IA buprenorphine, seven healthy horses were used in a randomized cross-over design. Temporary lameness resulting from acute synovitis was induced followingIA administration of lipopolysaccharide. Afterwards, horses received three different treatments: 1) IA buprenorphine (5 µg kg-1) plus intravenous saline, 2) IA saline plus intravenous buprenorphine (5 µg kg-1), and 3) IA saline plus intravenous saline. Each horse received each treatment with a washout period between treatments. Physiologic variables, lameness and pain scores were evaluated at stablished intervals over 48 hours, and synovial fluid and plasma for drug concentrations were determined at selected time-points over 24 hours.

Results from these studies show that a low concentration of buprenorphine does not have appreciable cytotoxic effects on equine chondrocytes in vitro. Buprenorphine was detectable in the synovial fluid for at least 24 hours post IAadministration, with no significant systemic absorption. Intra-articular administration of buprenorphine however, did not significantly improve lameness or pain scores when compared with the saline control. Pharmacodynamically, gastrointestinal sounds were decreased only for 4 hours in the IA and intravenous treatments when compared with saline.

Buprenorphine exhibits a concentration dependent cytotoxic effect in vitro. There was no significant analgesic effect of buprenorphine after IA administration, despite having detectable IA concentrations for at least 24 hours post-administration.

Committee Chair

Cremer, Jeannette

DOI

10.31390/gradschool_theses.5544

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