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首页> 外文期刊>Pain research & management: the journal of the Canadian Pain Society = journal de la socie?te? canadienne pour le traitement de la douleur >Evoked and Ongoing Pain-Like Behaviours in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy
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Evoked and Ongoing Pain-Like Behaviours in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy

机译：在紫杉醇诱发的周围神经病大鼠模型中诱发和持续的类似疼痛的行为

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Paclitaxel-induced neuropathic pain is a major dose-limiting side effect of paclitaxel therapy. This study characterises a variety of rat behavioural responses induced by intermittent administration of clinically formulated paclitaxel. 2?mg/kg paclitaxel or equivalent vehicle was administered intraperitoneally on days 0, 2, 4, and 6 to adult male Sprague-Dawley rats. Evoked pain-like behaviours were assessed with von Frey filaments, acetone, or radiant heat application to plantar hind paws to ascertain mechanical, cold, or heat sensitivity, respectively. Motor coordination was evaluated using an accelerating RotaRod apparatus. Ongoing pain-like behaviour was assessed via spontaneous burrowing and nocturnal wheel running. Mechanical and cold hypersensitivity developed after a delayed onset, peaked approximately on day 28, and persisted for several months. Heat sensitivity and motor coordination were unaltered in paclitaxel-treated rats. Spontaneous burrowing behaviour and nocturnal wheel running were significantly impaired on day 28, but not on day 7, indicating ongoing pain-like behaviour, rather than acute drug toxicity. This study comprehensively characterises a rat model of paclitaxel-induced peripheral neuropathy, providing the first evidence for ongoing pain-like behaviour, which occurs in parallel with maximal mechanical/cold hypersensitivity. We hope that this new data improve the face validity of rat models to better reflect patient-reported pain symptoms, aiding translation of new treatments to the clinic.
机译：紫杉醇引起的神经性疼痛是紫杉醇治疗的主要剂量限制副作用。这项研究的特点是间歇性给药临床配制的紫杉醇引起的多种大鼠行为反应。在成年雄性Sprague-Dawley大鼠第0、2、4和6天腹膜内给予2？mg / kg紫杉醇或同等载体。用von Frey细丝，丙酮或对足后爪施加辐射热来评估诱发的疼痛样行为，分别确定机械，冷或热敏感性。使用加速的RotaRod设备评估运动协调性。通过自发挖洞和夜间行车来评估持续的疼痛样行为。机械性和冷性超敏反应在延迟发作后出现，大约在第28天达到高峰，并持续数月。紫杉醇治疗的大鼠的热敏感性和运动协调性未改变。在第28天，自发的穴居行为和夜间轮转活动受到严重损害，但在第7天没有受到损害，表明正在进行的类似疼痛的行为，而不是急性药物毒性。这项研究全面表征了紫杉醇诱发的周围神经病的大鼠模型，为正在进行的疼痛样行为提供了第一个证据，这种行为与最大的机械/冷超敏反应同时发生。我们希望这些新数据能够改善大鼠模型的面部有效性，以更好地反映患者报告的疼痛症状，从而有助于将新疗法转化为临床药物。

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