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Paclitaxel-induced neuropathic hypersensitivity in mice: Responses in 10 inbred mouse strains

机译：紫杉醇诱导的小鼠神经性超敏反应：10种自交系小鼠的反应

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Mechanical allodynia, or hypersensitivity to tactile stimuli, is a frequent clinical symptom of neuropathy. Large interindividual differences have been observed in neuropathic pain, both in susceptibility to its development and in its severity. Identification of genetic factors relevant to this variability would be of obvious utility. Although many animal models of neuropathic pain following peripheral nerve injury have been developed, most involve intricate surgeries and are thus poorly suited for large-scale linkage mapping investigations in the mouse. Recently, a schedule of intraperitoneal injections of the chemotherapeutic agent, paclitaxel (Taxol), has been shown to produce a long-lasting, bilateral neuropathy in the rat, featuring hypersensitivity to mechanical, thermal and cold stimuli. We present here a survey of the responses of 10 inbred mouse strains to paclitaxel injections. Virtually all strains developed statistically significant mechanical allodynia, with one strain, DBA/2J, exhibiting especially robust changes. Strain sensitivities to paclitaxel-induced mechanical allodynia were similar to those obtained previously using a surgical model of neuropathic pain, supporting our contention that genetic sensitivity to mechanical allodynia is independent of the precise mode of induction. Using sensitive DBA/2 mice and a resistant strain, C57BL/6J, for comparison, we further characterized the paclitaxel model in mice by examining cold allodynia and thermal hyperalgesia. Both strains displayed equivalent cold allodynia but neither strain developed thermal hyperalgesia. The present data confirm a genetic component in mechanical allodynia using this model, while dissociating mechanical hypersensitivity from other pain modalities. (C) 2004 Elsevier Inc. All rights reserved. [References: 27]
机译：机械性异常性疼痛或对触觉刺激的超敏反应是神经病的常见临床症状。在神经性疼痛中，在其发展的敏感性和严重性方面都观察到很大的个体差异。鉴定与该变异性相关的遗传因素将具有明显的实用性。尽管已开发出许多周围神经损伤后神经性疼痛的动物模型，但大多数模型涉及复杂的手术，因此不适合用于小鼠的大规模连锁作图研究。最近，已经显示出腹膜内注射化学治疗剂紫杉醇（紫杉醇）的时间表可在大鼠中产生长期的双侧神经病，其特征在于对机械，热和冷刺激超敏反应。我们在这里介绍了10个近交小鼠品系对紫杉醇注射液反应的调查。实际上，所有菌株均出现统计学上显着的机械异常性疼痛，其中一种菌株DBA / 2J表现出特别强劲的变化。对紫杉醇诱发的机械性异常性疼痛的敏感性与以前使用神经性疼痛手术模型获得的敏感性相似，这支持了我们的观点，即对机械性异常性疼痛的遗传敏感性与精确的诱导方式无关。为了比较，使用敏感的DBA / 2小鼠和耐药株C57BL / 6J，我们通过检查冷异常性疼痛和热痛觉过敏进一步表征了紫杉醇模型。两种菌株均表现出同等的冷异常性疼痛，但均未出现热痛觉过敏。目前的数据证实了使用该模型的机械性异常性疼痛的遗传成分，同时使机械性超敏反应与其他疼痛方式分离。 （C）2004 Elsevier Inc.保留所有权利。 [参考：27]

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