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

Abstract

Highlights A large proportion of analgesics fail to translate from rodents to humans. Large animals share anatomical and behavioral similarities to humans. Studying large animals can provide novel insights for arthritic pain. In vitro techniques developed in rodents can be adopted in large animals.

Functional Characterization of Ovine Dorsal Root Ganglion Neurons Reveal Peripheral Sensitization after Osteochondral Defect

“…It has been previously proposed that large animals, such as sheep, can be leveraged as translational models to investigate mechanisms of joint pain in vitro due to their larger joint anatomy and DRG neuron diameter compared to rodents (Chakrabarti et al, 2020a). We provide proof using the ovine OD model (which is more translatable than rodent OD models)…”

“…Additionally, sheep DRG neurons could perhaps serve as better models than rodents for testing novel pain therapeutics, since rodents have different metabolic processes of drug breakdown and smaller sized neurons compared to humans (Chakrabarti et al, 2020a).…”

“…It has been previously proposed that large animals, such as sheep, can be leveraged as translational models to investigate mechanisms of joint pain in vitro because of their larger joint anatomy and DRG neuron diameter compared with rodents ( Chakrabarti et al, 2020a ). We provide proof using the ovine OD model (which is more translatable than rodent OD models) that it is possible to study neuronal constructs of peripheral sensitization in large animals using tools more widely used for analyzing rodent DRG neurons.…”

“…For example, preclinical orthopedic analysis of potential therapeutics, which tends to focus primarily on histologic assessment of cartilage integrity, could also directly analyze treatment effect on peripheral sensitization by recording the DRG neurons. Additionally, sheep DRG neurons could perhaps serve as better models than those of rodents for testing novel pain therapeutics, since rodents have different metabolic processes of drug breakdown and smaller sized neurons compared with humans ( Chakrabarti et al, 2020a ). However, to make use of large animals such as sheep fully feasible for pain research, efforts need to be made to develop effective tools.…”

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

“…We have previously proposed that large animals, such as sheep, can be leveraged as translational models to investigate mechanisms of joint pain in vitro due to their larger joint anatomy and DRG neuron diameter compared to rodents 12 . In this study we provide proof using the ovine OD model (which is difficult to induce in rodents) that it is possible to study neuronal constructs of peripheral sensitization in large animals using tools developed for rodent DRG neurons.…”