Development and validation of a porcine model of spinal cord injury-induced neuropathic pain

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Project Summary/ Abstract The goal of this project is to develop and validate a porcine model of spinal cord injury-induced neuropathic pain (SCI-NP). Most previous research in SCI-NP has been conducted in rodent models which have significantly advanced knowledge of mechanisms and drug discovery but have shortcomings which limit accurate prediction of analgesic efficacy in human clinical populations. Thus, a model that is more similar to humans in anatomy, size, metabolism, physiology, and pharmacokinetics/dynamics is needed to advance development of new therapies. We hypothesize that a porcine model of SCI-NP will be a useful translational intermediary as pigs are more similar to humans in all of these important attributes. The first aim of this proposal is to develop, characterize, and validate a porcine evoked pain scale using back-translated quantitative sensory testing (QST) methods to evaluate SCI-NP. We will use bioacoustics and pain interruption behaviors along with withdrawal responses to evaluate both supraspinal and reflex pain-like responses to evoked QST stimuli. We will evaluate the effects of SCI on neuropathic pain outcomes over time after SCI. To assess spontaneous pain responses, in aim 2 we will develop an ethologically-based sensory maze and evaluate bioacoustics, facial expression/ grimace, and maze performance behaviors. We will validate the evoked and spontaneous pain outcomes by assessing effects of pain medications commonly prescribed in the human clinical setting in this model and use histopathology to assess the recapitulation of this model to the human pathological condition. For aim 3, we will develop protocols to use an automated system for scoring the responses to both the evoked and spontaneous pain assays. We will also back-translate common data elements (CDEs) used in human neuropathic pain studies to the porcine model to enhance data sharing. The impact of this research will be the successful development of a clinically-relevant model of SCI- NP that can be used to significantly advance translational research for novel treatments.