Ovine model of neuropathic pain for assessing mechanisms of spinal cord stimulation therapy via dorsal horn recordings, von Frey filaments, and gait analysis

Chandan G Reddy,1 John W Miller,1 Kingsley O Abode-Iyamah,1 Sina Safayi,2 Saul Wilson,1 Brian D Dalm,1 Douglas C Fredericks,3 George T Gillies,4 Matthew A Howard III,1 Timothy J Brennan5 1Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA; 2Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, USA; 3Department of Orthopedics and Rehabilitation, University of Iowa Carver College of Medicine, Iowa City, IA, USA; 4Department of Mechanical and Aerospace Engineering, University of Virginia, Charlottesville, VA, USA; 5Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, IA, USA Background: It is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise. Purpose: Additionally, the small anatomic scale of current SCS animal models is a barrier to more translational research. Methods: Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact. Results: Detectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI. Conclusion: To our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS. Keywords: neuropathic pain, sheep models, gait analysis, spinal cord stimulation, unit recordings&nbsp