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Pain Hypersensitivity, Sensorimotor Impairment, And Decreased Muscle Force In A Novel Rat Model Of Radiation Induced Peripheral Neuropathy
Melissa Chantel Daniel, MD, Allison B. Vittert, BS, Noah S. Nelson, BS, MPH, Alexis Donneys, BS, MS, MD, Mary Jane Risch, BS, Amir Dehdashtian, BS, MD, MPH, Gina N. Sacks, BS, MD, Paul S. Cederna, MD, Steven R. Buchman, MD, Stephen W.P Kemp, PhD.
University of Michigan, Ann Arbor, MI, USA.

Purpose: 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 neuropathic pain, sensorimotor impairment, and muscle force parameters 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-radiated 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 sensorimotor and pain behavioral tests. Sensorimotor 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: Animals that underwent radiation treatment displayed significantly greater pain hypersensitivity to mechanical stimulation as compared to sham radiated controls from weeks 4-8 of testing. SFI values indicated sensorimotor impairments in the overground gait of radiated animals as compared to non-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 significant pain hypersensitivity, impairments in sensorimotor locomotion, 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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