Longitudinal multimodal assessment of neuropathy in a porcine neuritis model.

Abstract

BACKGROUND: Evaluation of animal models is critical in pre-clinical therapeutic research to determine translation potential. Due to their anatomic and physiological resemblance to humans, porcine models are a critical step prior to human translation. Our work evaluates long-term anatomic and behavioral effects (n = 9) over 8 weeks post-neuritis-induction surgery of the common peroneal nerve (CPN). NEW METHOD: This model utilizes longitudinal MRI and histological analysis of nerve and muscle, in addition to the use of the algometer and feather test as quantitative sensory testing methods. RESULTS: Neuritis animals showed heightened rear leg sensitivity on the neuritis side, with significant reduction in maximum tolerated pressure in the majority of dermatomes and significant heightened sensitivity to light touch stimuli. Significant muscle loss was well defined with short- and long-term assessments. MR imaging showed increased signal intensity in CPN-innervated muscles alongside reduction in volume and hypotonia. Histology supports these conclusions as evidenced by the presence of atrophied fibers, fibrosis, and fatty infiltrations. At necropsy, there was an average of 50 % reduction in CPN-innervated muscle weights compared to control leg muscles. Pigs experienced postural and ambulatory abnormalities without inhibiting regular activity. COMPARISON WITH EXISTING METHOD(S): We expand on established protocols for assessing neuropathic pain (Castel et al., 2016; Hellman et al., 2021b), which assess short-term effects (10 days - 4 weeks) of a peripheral nerve injury. CONCLUSION: We have demonstrated and evaluated a longitudinal chronic neuropathic pain porcine model. Variables including medication regime and anatomic sequelae need to be considered as they may affect the quantitative sensory testing and time course of testing.