辐射诱发周围神经病变的新型大鼠模型中的痛觉过敏、感觉运动损伤和肌力下降。

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY
Allison B Vittert, Melissa Daniel, Shelby R Svientek, Mary Jane Risch, Noah S Nelson, Alexis Donneys, Amir Dehdashtian, Gina N Sacks, Steven R Buchman, Stephen W P Kemp
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引用次数: 0

摘要

简介辐射诱发的周围神经病变是一种罕见但严重的并发症,通常会导致严重的发病率、终身残疾和慢性疼痛。不幸的是,这种类型的周围神经病变通常是进行性的,而且几乎总是不可逆的。迄今为止,辐射诱发周围神经病变的标准化大鼠模型尚未建立。本研究的目的是在大鼠模型中检测临床相关辐射剂量给药后的神经病理性疼痛、感觉运动损伤和肌力参数:十只大鼠被随机分配到两个实验组中的一个:(1) 辐射组和 (2) 假辐射对照组。辐射动物接受了 35 Gray (Gy) 的临床相关剂量,每天分为五次,每次 7 Gy。该方案的人体等效剂量为 70 Gy,与肿瘤患者接受放射治疗时使用的剂量相近。假辐射对照组被麻醉后放入辐射装置中,但不接受辐射。所有动物都接受了感觉运动和疼痛行为测试的基线值测试。感觉运动测试包括评估行走轨迹和计算坐骨神经功能指数(SFI)。疼痛相关行为测试包括机械异感(von Frey 试验)、冷异感(丙酮试验)和热异感(哈格里夫斯试验)。对动物进行了为期 8 周的连续测试。在研究终点,完成了电生理学和肌力评估,并对所有坐骨神经进行了组织形态分析:结果:与假放射对照组相比,接受放射治疗的动物在第 4 至第 8 周的测试中对机械刺激的痛觉过敏度明显升高。SFI值表明,与未接受放射治疗的动物相比,接受放射治疗的动物在地面步态方面存在感觉运动障碍。此外,与假辐射对照组相比,辐射动物的抽搐和四肢肌力均有所下降:结论:对大鼠进行与临床相关的人体等效剂量 35 Gy 分段放射治疗后,大鼠会出现明显的痛觉过敏、感觉运动障碍和肌肉力量下降。这种辐射诱发周围神经病变的新型啮齿类动物模型可用于评估治疗方法的潜在疗效,以预防或缓解这种使人衰弱的临床症状。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pain hypersensitivity, sensorimotor impairment, and decreased muscle force in a novel rat model of radiation-induced peripheral neuropathy.

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 neuropathic pain, sensorimotor impairment, and muscle force parameters following the 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 five daily doses of 7 Gy/day. This regimen represents a human equivalent dose of 70 Gy, approximating the same dosage utilized for radiotherapy in oncologic patients. 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 the evaluation of walking tracks with the 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 the study endpoint, electrophysiological and muscle force assessments were completed, and histomorphometric analysis was performed on all sciatic nerves.

Results: Animals that underwent radiation treatment displayed significantly greater pain hypersensitivity to mechanical stimulation as compared to sham radiated controls from weeks 4 to 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 human equivalent dose of fractionated 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 potential efficacy of therapeutic treatments to either prevent or remediate this clinically debilitating condition.

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来源期刊
CiteScore
6.10
自引率
7.90%
发文量
45
审稿时长
>12 weeks
期刊介绍: The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.
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