“Patient reported outcomes” following experimental surgery—using telemetry to assess movement in experimental ovine models

Abstract

Many potential treatments for orthopedic disease fail at the animal to human translational hurdle. One reason for this failure is that the majority of pre‐clinical outcome measurements emphasize structural changes, such as gross morphology and histology, and do not address pain or its alleviation, which is a key component of treatment success in man. With increasing emphasis on “patient reported outcome measurements (PROM)” in clinical practice, in this study we have used two different telemetric methods (geolocation and Fitbark activity trackers, Kansas City, MO) to measure movement behavior, i.e., an indirect PROM, in an ovine osteoarthritis induction and an osteochondral defect model performed in adult female Welsh Mountain sheep. This study demonstrates that both systems can be used to track movement and activity of experimental sheep before and after surgery and that the Geolocator system recorded a decrease in distance moved and activity at the end of the experimental period in both models. The Fitbark activity tracker also recorded significant alterations in movement behavior at the end of these studies and this method of recording showed a correlation between Fitbark data and radiography, macroscopic and histological scoring (well recognized outcome measurements), particularly in animals with large (10 mm) defects, i.e., more severe pathology. These results suggest that telemetry is able to track movement behavior in experimental sheep and that the methodology should be considered for inclusion in outcome measures in preclinical orthopedic research. © 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:1498–1507, 2018.

Analgesia for Sheep in Commercial Production: Where to Next?

“…Use of telemetry and geolocation using movement trackers was effective at assessing pain in sheep with induced osteoarthritis [ 77 ]. In addition, stride length and number of steps were good indicators of post-castration pain in cattle [ 78 ].…”

Functional characterization of ovine dorsal root ganglion neurons reveals peripheral sensitization after osteochondral defect

“…pentobarbitone sodium at 2, 4, and 6 weeks post-surgery. A semiquantitative histological analysis using International Cartilage Repair Society macroscopic score was carried out blindly as previously established 5 .…”

“…The thinner cartilage in rodents restricts the amount of damage that can be induced, and therefore is less translatable to the human disease. In contrast, large animals, such as sheep, have a similar cartilage volume (359 mm 3 ) to humans and OD can successfully be induced in their joints as evidenced by histological scoring and reduced activity 4,5 . Consequently, the majority of OD research is focused on developing strategies for bone and cartilage regeneration, such as implantation of biomaterials in large animal models 4 .…”

Peripheral mechanisms of arthritic pain: A proposal to leverage large animals for in vitro studies

“…Simpler methods have also been developed to quantify force applied by each limb using pressure mat systems ( Uilenreef et al, 2019 ) or force plates on treadmills ( Belshaw et al, 2016 ). Additionally, telemetry based analysis of distance travelled in freely moving animals has also shown promise for evaluating pain behavior in sheep ( Newell et al, 2018 ). Besides lameness, inflammation is another widely assessed in vivo outcome in arthritis models, although it should be noted that although inflammation and pain often occur concomitantly, inflammation can occur in the absence of pain and vice versa ( Bedson and Croft, 2008 , Salaffi et al, 2018 ).…”

“…The field of large animal research has used, and continues to rely mostly on, histological analysis of joints using a modified Mankin or O’Driscoll scoring system ( Abdalmula et al, 2014 , Haak et al, 1996 , Naujokat et al, 2019 , Newell et al, 2018 ), often accompanied by protein level immunoprecipitation of inflammatory mediators such as prostaglandins E2 (PGE2), IL-6 and IL-1 β, TNF- α in the serum, synovial fluid and/or synovium tissue ( Barrachina et al, 2016 , Neuenschwander et al, 2019 , Owens et al, 1996 ). A handful of studies have also revealed expression of pain-related proteins (e.g.…”