Establishment of Pain Hypersensitivity, Gait Impairment, and Decreased Muscle Force in a Novel Rat Model of Radiation Induced Peripheral Neuropathy
Allison B Vittert, MS1, Mary Jane Risch, BS1, Noah S Nelson, BSc2, Alexis Donnelys, MD2, Amir Dehdashtian, MD, MPH1, Gina N Sacks, MD1, Paul S Cederna, MD3, Steven R. Buchman, MD4 and Stephen WP Kemp, PhD1, (1)University of Michigan, Ann Arbor, MI, (2)The University of Michigan, Ann Arbor, MI, (3)Plastic Surgery, University of Michigan, Ann Arbor, MI, (4)Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI
Introduction: Radiation induced peripheral neuropathy is a rare but serious complication often resulting in profound morbidity, life-long disability, and chronic debilitating pain. Unfortunately, this type of peripheral neuropathy is usually progressive, and almost always irreversible. To date, a standardized rat model of radiation induced peripheral neuropathy has not been established. The purpose of the present study was to examine both locomotor impairments and neuropathic pain behavior following administration of a clinically relevant radiation dose in a rat model.
Methods: Ten rats were randomly assigned to one of two experimental groups: (1) radiation, and; (2) sham-radiation controls. Radiated animals were given a clinically relevant dose of 35 Gray (Gy) divided into 5 daily doses of 7 Gy/day. Sham-radiated controls were anesthetized and placed in the radiation apparatus, but were not given radiation. All animals were tested for baseline values in both overground locomotion and pain behavioral tests. Overground locomotion testing consisted of evaluation of walking tracks with calculation of the Sciatic Functional Index (SFI). Pain related behavioral measures consisted of mechanical allodynia (von Frey test), cold allodynia (Acetone test), and thermal allodynia (Hargreaves test). Animals were tested serially over an 8 week period. At study endpoint, electrophysiological and muscle force assessment were completed, and all sciatic nerves were taken for histomorphometric analysis.
Results: All radiated animals tolerated the procedure. Animals that underwent radiation displayed significantly greater hypersensitivity to mechanical stimulation as compared to sham radiated controls. SFI values indicated impairments in the overground gait of radiated animals. Furthermore, radiated animals displayed reduced twitch and tetanic muscle force when compared to sham radiated controls.
Conclusions: A clinically relevant radiation dose of 35 Gy in rats established impairments in overground locomotion, chronic pain hypersensitivity, and decreased muscle force capacity. This novel rodent model of radiation induced peripheral neuropathy can be utilized to assess the effect of pharmacological treatments on this debilitating condition.
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