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Nocifensive Behavior and Transcriptomic Biomarkers in a Translational Pig Model of Spared Nerve Injury

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2023
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dissertation
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Neuropathic pain is a prevalent condition that significantly impacts quality of life. Translational animal models are needed to understand the mechanisms and develop novel treatments. The spared nerve injury (SNI) model is a well-validated neuropathic pain model that causes allodynia and hyperalgesia. While the SNI was originally developed in rats, rodent models have translational limitations. Pigs, by contrast, share many characteristics with humans, making them uniquely suitable for modeling painful conditions. Objective: The goal of this study was to test the feasibility and efficacy of a translational pig model of SNI. Methods: The left common peroneal nerve of SNI pigs was ligated, while the nerve remained untouched in sham pigs. Mechanical and dynamic allodynia, thermal hyperalgesia, pressure, and gait alterations were assessed over four weeks. Video footage was recorded during testing and analyzed for a pig grimace scale. Blood and spinal cord tissue were harvested and sequenced to determine the presence of differentially expressed genes and associated enriched pathways. Results: Surgical ligation of the common peroneal nerve was feasible and safe. However, there were significant floor and ceiling effects for mechanical and dynamic allodynia and thermal hyperalgesia testing. Females showed lower pressure tolerance than males over time at the medial left (p=0.003), medial right (p=0.003), lateral left (p=0.041), and lateral right (p=0.003) testing locations. The left side had a lower threshold tolerance than the right side for both medial (p<0.001) and lateral (p=0.03) locations, although this difference was not significant over time. There was no significant difference in threshold tolerance between the sham and SNI groups. There were no significant changes in gait. The grimace scale showed substantial interrater reliability for ear position (kappa=0.73) and moderate interrater reliability for snout tension (kappa=0.43). Several pathways related to inflammation and wound healing were differentially expressed between the SNI versus sham groups and left versus right sides of the SNI animals. Conclusion: While the pig model of SNI is feasible, special considerations are needed when acclimating animals and calibrating study equipment to avoid floor and ceiling effects. Relevant enriched pathways may be targets of interest for future neuropathic pain research.

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University of Maryland, Baltimore, School of Nursing, Ph.D., 2023
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